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323
  
1/1/2024Rx.01.247CommercialOyenusi, Oluwadamilola

​

Hutchinson-Gilford Progeria Syndrome is sporadic, very rare, autosomal dominant, deadly childhood disorder. It is one of the progeroid syndromes also known as Hutchinson-Gilford progeria syndrome (HGPS). Aging is a developmental process that begins with fertilization and ends up with death involving a lot of environmental and genetic factors. The disease firstly involves premature aging and then death from complications of atherosclerosis such as myocardial infarction, stroke, atherosclerosis, or heart failure.

Progeroid laminopathies are characterized by the premature appearance of certain signs of physiological aging in a subset of tissues. They are caused by mutations in genes coding for A-type lamins or lamin-binding proteins.

Lonafarnib inhibits farnesyltransferase to prevent farnesylation and subsequent accumulation of progerin and progerin-like proteins in the inner nuclear membrane.

Zokinvy is indicated in patients 12 months of age and older with a body surface area (BSA) of 0.39 m2 and above:

  • To reduce the risk of mortality in Hutchinson-Gilford Progeria Syndrome (HGPS)
  • For the treatment of processing-deficient Progeroid Laminopathies with either:
    • Heterozygous LMNA mutation with progerin-like protein accumulation
    • Homozygous or compound heterozygous ZMPSTE24 mutations


 

​The intent of this policy is to communicate the medical necessity criteria for Lonafarnib (Zokinvy™) as provided under the member's prescription drug benefit. 


INITIAL CRITERIA Lonafarnib (Zokinvy™) is approved when ALL of the following are met:

  1. Submission of medical records (e.g., chart notes, lab values) confirming one of the following:
    1. Diagnosis of Hutchinson-Gilford Progeria Syndrome; or
    2. Genetic testing results confirming a LMNA mutation that results in the production of progerin; or
    3. Processing-deficient Progeroid Laminopathies with one of the following:
      1. Genetic testing results confirming member has a heterozygous LMNA mutation with progerin-like protein accumulation; or
      2. Genetic testing results confirming member has a homozygous or compound heterozygous ZMPSTE24 mutations; and
  2. Member is 12 months of age or older; and
  3. Member has a body surface are of 0.39 m2 and above; and
  4. Prescribed by or in consultation with a specialist with expertise in the diagnosis and management of Progeria

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA Lonafarnib (Zokinvy™) is re-approved when all of the following have been met:
  1. Documentation that member has had clinical benefit with the requested drug; and
  2. Prescribed by or in consultation with a specialist with expertise in the diagnosis and management of Progeria

Reauthorization duration: 2 years



 


​N/A

Ahmed MS, Ikram S, Bibi N, Mir A. Hutchinson-Gilford Progeria Syndrome: A Premature Aging Disease. Mol Neurobiol. 2018 May;55(5):4417-4427. doi: 10.1007/s12035-017-0610-7. Epub 2017 Jun 28. PMID: 28660486. Accessed  December 06, 2023.

 

Marcelot A, Worman HJ, Zinn-Justin S. Protein structural and mechanistic basis of progeroid laminopathies. FEBS J. 2021 May;288(9):2757-2772. doi: 10.1111/febs.15526. Epub 2020 Sep 3. PMID: 32799420. Accessed December 06, 2023.

 

Zokinvy™ (lonafarnib) [package insert]. Alto, CA; Eiger BioPharmaceuticals, Inc.; Revised November 2020. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213969s000lbl.pdf Accessed December 06, 2023.
​

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​

Rx.01.33 Off Label Use​


 

​

Brand Name Generic Name
Zokinvy™Lonafarnib


 

333
  
1/1/2024Rx.01.283CommercialOyenusi, Oluwadamilola

​Clostridioides difficile infection (CDI) is one of the most common hospital-acquired (nosocomial) infections and is an increasingly frequent cause of morbidity and mortality among older adult hospitalized patients. C difficile is highly transmissible via the fecal-oral route by ingestion of spores. Recurrent CDI is defined by resolution of CDI symptoms while on appropriate therapy, followed by reappearance of symptoms, usually within two months of discontinuing treatment. Management of a first CDI recurrence consists of antibiotic therapy.

VOWST is indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in individuals 18 years of age and older following antibacterial treatment for recurrent CDI (rCDI).  

Limitation of Use: VOWST is not indicated for treatment of CDI.


​The intent of this policy is to communicate the medical necessity criteria for Fecal microbiota spores, live-brpk (Vowst™) as provided under the member's prescription drug benefit. 

​

Fecal microbiota spores, live-brpk (Vowst™) is approved when ALL of the following are met:

  1. Diagnosis of recurrent clostridioides difficile infection (CDI) as defined by both of the following:
    1. Presence of diarrhea defined as a passage of 3 or more loose bowel movements within a 24-hour period for 2 consecutive days; and
    2. A positive stool test for C. difficile toxin or toxigenic C. difficile; and
  2. Member is 18 years of age or older; and
  3. Member has a history of two or more recurrent episodes of CDI within 12 months; and
  4. ALL of the following:
    1. Member has completed at least 10 consecutive days of one of the following antibiotic therapies 2-4 days prior to initiating Vowst:
      1. Oral vancomycin; or
      2. Dificid (fidaxomicin); and
    2. Member has completed the recommended bowel prep (e.g. 296mL of magnesium citrate) the day before and at least 8 hours prior to initiating Vowst; and
    3. Previous episode of CDI is under control (e.g., less than 3 unformed/loose [i.e., Bristol Stool Scale type 6-7] stools/day for 2 consecutive days); and
  5. Prescribed by or in consultation with one of the following:
    1. Gastroenterologist; or
    2. Infectious disease specialist

 

Authorization duration: 14 days


​N/A

​

VOWST™ (fecal microbiota spores, live-brpk) [package insert]. Brisbane, CA: Aimmune Therapeutics, Inc. April 2023. Available from: https://www.serestherapeutics.com/our-products/VOWST_PI.pdf. Accessed November 20, 2023.


Lamont JT. Clostridioides difficile infection in adults: Epidemiology, microbiology, and pathophysiology. In: UpToDate, Post TW (Ed), Wolters Kluwer. Jan 2023. Available from: https://www.uptodate.com. Accessed November 20, 2023.


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​

Rx.01.33 Off Label Use

Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit Rx.01.76​


​

Brand NameGeneric Name
Vowst™ fecal microbiota spores, live-brpk


334
  
1/1/2024Rx.01.281CommercialOyenusi, Oluwadamilola

​

Natural menopause is defined as the permanent cessation of menstrual periods, determined retrospectively after a person with menstrual periods has experienced 12 months of amenorrhea without any other obvious pathologic or physiologic cause. This results in low serum estradiol concentrations and vasomotor symptoms (hot flashes). It occurs at a median age of 51. Hot flashes occur in approximately 75 to 80 percent of menopausal people in the United States. Hormone therapy remains the most effective treatment for hot flashes.

 

Fezolinetant is a neurokinin 3 (NK3) receptor antagonist that blocks neurokinin B (NKB) binding on the kisspeptin/neurokinin B/dynorphin (KNDy) neuron to modulate neuronal activity in the thermoregulatory center. Fezolinetant has high affinity for the NK3 receptor (Ki value of 19.9 to 22.1 nmol/L), which is more than 450-fold higher than binding affinity to NK1 or NK2 receptors.

 

VEOZAH (fezolinetant) is indicated for the treatment of moderate to severe vasomotor symptoms due to menopause.


​The intent of this policy is to communicate the medical necessity criteria for Fezolinetant (Veozah™) as provided under the member's prescription drug benefit. 

​

INITIAL CRITERIA: Fezolinetant (Veozah™) is approved when all of the following criteria are met:

  1. Diagnosis moderate to severe vasomotor symptoms due to menopause; and
  2. Inadequate response or inability to tolerate a minimum 30-day supply of both of the following:
    1. Menopausal hormone therapy (e.g., generic estradiol vaginal cream, generic estradiol vaginal tablet); and
    2. Non-hormonal therapy (e.g., paroxetine mesylate, venlafaxine hcl, clonidine, etc.)

 

Initial authorization duration: 6 months

 

REAUTHORIZATION CRITERIA: Fezolinetant (Veozah™) is re-approved with documentation of positive clinical response to therapy (e.g., decrease in frequency and severity of vasomotor symptoms from baseline, etc.)

 

Reauthorization duration: 12 months


​N/A

​

VEOZAH (fezolinetant) [package insert]. Northbrook, IL: Astellas Pharma US, Inc. May 2023. Available from: https://www.astellas.com/us/system/files/veozah_uspi.pdf. Accessed November 20, 2023.

 

Santen RJ. Menopausal hot flashes. In: UpToDate, Post TW (Ed), Wolters Kluwer. August 2023. Available from: https://www.uptodate.com. Accessed November 20, 2023.


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​Rx.01.33 Off Label Use​

​

Brand NameGeneric Name
Veozah™Fezolinetant


335
  
1/1/2024Rx.01.282CommercialOyenusi, Oluwadamilola

​

Activated PI3 kinase delta syndrome (APDS) is a primary immunodeficiency caused by dominant mutations that increase activity of phosphoinositide-3-kinase δ (PI3Kδ). APDS can be caused by mutations in the PIK3CD gene that encodes PI3Kδ catalytic subunit p110δ (APDS1) or mutations in the PIK3R1 gene that encodes regulatory subunit p85α (APDS2). Patients with APDS disease have recurrent sinopulmonary infections with progressive airway damage and bronchiectasis, lymphadenopathy, nodular lymphoid hyperplasia in mucosal tissues, increased incidence of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) viremia and EBV-related lymphoma, progressive lymphopenia, elevated serum IgM, and impaired antibody responses.

 

Leniolisib inhibits PI3K-delta by blocking the active binding site of PI3K-delta. In cell-free isolated enzyme assays, leniolisib was selective for PI3K-delta over PI3K-alpha (28-fold), PI3K-beta (43-fold), and PI3K-gamma (257-fold), as well as the broader kinome. In cell-based assays, leniolisib reduced pAkt pathway activity and inhibited proliferation and activation of B and T cell subsets. Gain-of-function variants in the gene encoding the p110-delta catalytic subunit or loss of function variants in the gene encoding the p85-alpha regulatory subunit each cause hyperactivity of PI3K-delta. Leniolisib inhibits the signalling pathways that lead to increased production of PIP3, hyperactivity of the downstream mTOR/Akt pathway, and to the dysregulation of B and T cells.

 

JOENJA® (leniolisib) is indicated for the treatment of activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) in adult and pediatric patients 12 years of age and older.


​The intent of this policy is to communicate the medical necessity criteria for Leniolisib (Joenja®) as provided under the member's prescription drug benefit. 

​

INITIAL CRITERIA: Leniolisib (Joenja®) is approved when all of the following are met:

  1. Diagnosis of activated phosphoinositide 3-kinase delta syndrome (APDS); and
  2. Molecular genetic testing confirms mutations in the PIK3CD or PIK3R1 gene; and
  3. Member is 12 years of age or older; and
  4. Member weighs greater than or equal to 45kg; and
  5. Both of the following:
    1. Presence of nodal and/or extranodal proliferation (e.g., lymphadenopathy, splenomegaly, hepatomegaly); and
    2. Presence of other clinical findings and manifestations consistent with APDS (e.g., recurrent sino-pulmonary infections, bronchiectasis, enteropathy); and
  6. Inadequate response or inability to tolerate at least one standard of care treatment for APDS (e.g., Immunoglobulin replacement therapy, antimicrobial prophylaxis [e.g., azithromycin, Bactrim], rituximab, tacrolimus, etc.); and
  7. Prescribed by or in consultation with one of the following:
    1. Hematologist; or
    2. Immunologist

 

Initial authorization duration: 6 months

 

REAUTHORIZATION CRITERIA: Leniolisib (Joenja®) is re-approved with documentation of positive clinical response to therapy (e.g., reduced lymph node size, increased naïve B-cell percentage, decreased severity or frequency of infections/hospitalizations)

 

Reauthorization duration: 12 months

 


​N/A

​

Michalovich D, Nejentsev S. Activated PI3 Kinase Delta Syndrome: From Genetics to Therapy. Front Immunol. 2018 Feb 27;9:369. doi: 10.3389/fimmu.2018.00369. PMID: 29535736; PMCID: PMC5835040.

 

Notarangelo LD. Hyperimmunoglobulin M syndromes. In: UpToDate, Post TW (Ed), Wolters Kluwer. May 2023. Available from: https://www.uptodate.com. Accessed November 20, 2023.

 

JOENJA® (leniolisib) [package insert]. Saint Quentin Fallavier, France: Pharming Technologies B.V. March 2023. Available from:

https://joenja.com/prescribing-information.pdf. Accessed November 20, 2023.


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​Rx.01.33 Off Label Use​

​

Brand NameGeneric Name
Joenja®Leniolisib


337
  
4/1/2024Rx.01.2CommercialOyenusi, OluwadamilolaQ4-2023

Age edits are used to ensure appropriate utilization in certain age groups.  An age edit may be placed on a medication when there are concerns for safe use or inappropriate utilization based on indication in a particular age group. Age edits may be based on the FDA approved label, available literature or accepted compendia as listed in the Off-Label Use Policy. When a medication listed below is prescribed to a member outside of the defined age range, the age edit will be applied and prior authorization will be required. 

Retinoids: adapelene (Differin®), tazarotene (Avage®, Tazorac®) and Tretinoin, topical (e.g. Atralin®, Avita®, Retin-A®, Retin A micro®, Altreno™, etc), triafarotene (Aklief®).

Topical retinoids may be used for cosmetic indications, including fine lines and wrinkles, in addition to treating acne.  Coverage of medications intended for cosmetic indications is an excluded benefit.  Studies of topical retinoids for fine lines and wrinkles included patients beginning in their 20s.  An age edit for members over the age of 25 years will be applied to ensure indication is not cosmetic.

Alzheimer medications:Donepezil (Aricept® [ODT]), Rivastigmine (Exelon®), Memantine (Namenda® [XR]), Galantamine (Razadyne® [ER]), Memantine/ donepezil (Namzaric®))

Studies for Alzheimer's disease were primarily conducted in patients over the age of 50 years.  An age edit will be applied to evaluate indication in members under the age of 50 years.

Oral liquids: Age edits may be applied to liquid dosage forms that have a tablet or capsule with the same indication to limit use to those under age 12 years.  Studies show that children as young as 6-11 years of age can be taught how to swallow solid dosage forms. 

Benign Prostate Hypertrophy (BPH); Dutasteride (Avodart®), Finasteride (Proscar®): Studies for BPH indicate this condition is most prevalent in men over the age of 50 years. An age edit will be applied to evaluate indication in members under the age of 50 years.


The intent of this policy is to communicate the medical necessity criteria for medications that have age edits as provided under the member’s prescription drug benefit.

The drugs in the following table are approved in the age ranges listed when there is documentation of all of the following:

  1. FDA or compendia approved indication; and
  2. Not used for an indication that is otherwise excluded (i.e., cosmetic); and
  3. Oral liquid dosage forms that have a tablet or capsule formulation available, one of the following:  
    1. Drug will be administered via nasogastric or gastronomy tube; or
    2. Member is unable to swallow an intact capsule or tablet

 

***Note: Age edits apply to brand and generic products.  Some brand name products have prior authorization in addition to age edit. 
Authorization Duration: 2 years 


Opioids (Butorphanol tartrate NS, Ultram®, Ultram ER®, Ultracet®, Conzip®, codeine containing products, hydrocodone containing cough and cold products)

  • Exposes patients and others to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing and monitor all patients regularly for the development of these behaviors and conditions.  
  • Serious, life-threatening, or fatal respiratory depression may occur with use. Monitor for respiratory for respiratory depression, especially during initiation or following a dose increase.
  • Accidental exposure, especially by children, can result in fatal overdose.
  • Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatalogy experts.
  • Interactions with drugs affecting cytochrome P450 isoenzymes: the concomitant use of butorphanol tartrate NS with all cytochrome P450 3A4 inhibitors may result in an increase in butorphanol plasma concentrations, which could increase or prolong adverse reactions and potentially fatal respiratory depression. Discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in butorphanol concentration. The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol or codeine are complex and requires careful consideration of the effects on the parent drug and the active metabolite.  
  • Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

Treximet® (sumatriptan/naproxen):

  • May cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. Treximet® is contraindicated in the setting of coronary artery bypass graft.
  • NSAID containing products cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events.

ACE inhibitors (Epaned®, Qbrelis®):

  • Fetal toxicity. When pregnancy is detected discontinue Epaned®/Qbrelis® as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

Benzodiazepines (Clobazem, Halcion®, Doral®, Restoril®, Ativan®, Onfi®, Oxazepam®, Tranxene®, Chlordiazepoxide, Estazolam, Flurazepam and Xanax®):

  • Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and duration to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.  
  • The use of benzodiazepines exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Before prescribing benzodiazepine and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction. 
  • Abrupt discontinuation or rapid dosage reduction of benzodiazepines after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue the benzodiazepine or reduce the dosage. 

Non-Steroidal Anti-Inflammatory Drugs (Naprosyn®, Indocin®)

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.
  • Naprosyn® and Indocin® are contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
  • NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

Nortriptyline

  • Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of nortriptyline hydrochloride or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Nortriptyline hydrochloride is not approved for use in pediatric patients.

Xatmep™ (methotrexate oral solution):

  • Methotrexate can cause severe or fatal toxicities. Monitor closely and modify dose or discontinue for the following toxicities: bone marrow suppression, infection, renal, gastrointestinal, hepatic, pulmonary, hypersensitivity, and dermatologic. Methotrexate can cause embryo-fetal toxicity and fetal death. Use in polyarticular juvenile idiopathic arthritic arthritis is contraindicated in pregnancy. Consider the benefits and risks of Xatmep™ and risks to the fetus when prescribing Xatmep™ to a pregnant patient with a neoplastic disease. Advise patients to use effective contraception during and after treatment with Xatmep™.

Tegretol® (carbamazepine):

  • Serious and sometimes fatal dermatologic reactions, including Toxic Epidermal Necrolysis (TEN) and Stevens-Johnson Syndrome (SJS), have been reported during treatment with Tegretol®. Studies in patients of Chinese ancestry have found a strong association between the risk of developing TEN/SJS and the presence of HLA-b*1502, an inherited allelic variant of the HLA-b gene. HLA-b*1502 is found almost exclusively in patients with ancestry across broad areas of Asia. Patients with ancestry in genetically at-risk populations should be screened for the presence of HLA-b*1502 prior to initiating treatment with Tegretol®. Patients testing positive for the allele should not be treated with Tegretol® unless the benefit clearly outweighs the risk.
  • Aplastic anemia and agranulocytosis have been reported in association with the use of Tegretol®. Data from a population-based case control study demonstrate that the risk of developing these reactions is 5-8 times greater than in the general population. However, the overall risk of these reactions in the untreated general population is low, approximately six patients per one million population per year for agranulocytosis and two patients per one million population per year for aplastic anemia. Although reports of transient or persistent decreased platelet or white blood cell counts are not uncommon in association with the use of Tegretol®, data are not available to estimate accurately their incidence or outcome. However, the vast majority of the cases of leukopenia have not progressed to the more serious conditions of aplastic anemia or agranulocytosis. Because of the very low incidence of agranulocytosis and aplastic anemia, the vast majority of minor hematologic changes observed in monitoring of patients on Tegretol® are unlikely to signal the occurrence of either abnormality. Nonetheless, complete pretreatment hematological testing should be obtained as a baseline. If a patient in the course of treatment exhibits low or decreased white blood cell or platelet counts, the patient should be monitored closely. Discontinuation of the drug should be considered if any evidence of significant bone marrow depression develops.

 

Riomet® [ER] (metformin):

  • Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio; and metformin plasma levels generally > 5 mcg/mL.
  • Risk factors include renal impairment, concomitant use of certain drugs, age ≥ 65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the Full Prescribing Information.
  • If lactic acidosis is suspected, discontinue Riomet institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

 

Proazac® (fluoxetine)

  • Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants.
  • Monitor for worsening and emergence of suicidal thoughts and behaviors.

Qdolo™ (tramadol)

  • Ensure accuracy when prescribing, dispensing, and administering QDOLO. Dosing errors due to confusion between mg and mL can result in accidental overdose and death
  • QDOLO exposes users to the risks of addiction, abuse and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing QDOLO, and monitor regularly for these behaviors or conditions.
  • To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products.
  • Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially during initiation or following a dose increase.
  • Accidental ingestion of QDOLO, especially by children, can result in a fatal overdose of tramadol.
  • Life-threatening respiratory depression and death have occurred in children who received tramadol. Some of the reported cases followed tonsillectomy and/or adenoidectomy; in at least one case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism
  • QDOLO is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy (4). Avoid the use of QDOLO in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol.
  • Prolonged use of QDOLO, during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life threatening if not recognized and treated. If prolonged opioid use is required in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
  • The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with QDOLO requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1.
  • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.

Thyquidity™ (levothyroxine sodium)

  • Thyroid hormones, including THYQUIDITY, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.
Valcyte® (valganciclovir)
 
  • Hematologic Toxicity: Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, and bone marrow failure including aplastic anemia have been reported in patients treated with VALCYTE. 
  • Impairment of Fertility: Based on animal data and limited human data, VALCYTE may cause temporary or permanent inhibition of spermatogenesis in males and suppression of fertility in females.
  • Fetal Toxicity: Based on animal data, VALCYTE has the potential to cause birth defects in humans.
  • Mutagenesis and Carcinogenesis: Based on animal data, VALCYTE has the potential to cause cancers in humans.​

Accolate® (zafirlukast) [prescribing information]. Wilmington, DE: Par Pharmaceuticals; December 2015. Accessed February 13, 2024
 
Aczone® (dapsone) [prescribing information]. Irvine, CA: Allergan; September 2019. https://www.almirall.us/pdf/aczone_7-5_pi_2019-09.pdf. Accessed February 13, 2024.
 
Adlarity® (donepezil transdermal system) [prescribing information]. Grand Rapids, MI: Corium Inc; March 2022. Available from: https://corium.com/products/ADLARITY/ADLARITY_PI_ENGLISH_US.pdf. Accessed February 13, 2024.
 
Aklief® (trifarotene) [prescribing information]. Fort Worth, TX: Galderma Laboratories, L.P.: October 2019. Available at: https://www.galderma.com/us/sites/g/files/jcdfhc341/files/2019-10/10-2-2019%20Revised%20PI%20NDA%20211527.pdf. Accessed February 13, 2024.
 
Altreno™ (tretinoin) [prescribing information]. Bridgewater, NJ: Valeant Pharmaceutical North America LLC. March 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1412aba5-71aa-4cce-8db4-c189bed1852c&type=display. Accessed February 13, 2024.
 
Atralin™ (tretinoin) [prescribing information]. Fort Worth, TX: Coria Laboratories, LTD.; July 2016. Revised July 2016. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b45969-a64a-4ce3-b3b6-157d2568a301&type=display Accessed February 13, 2024.
 
Amerge® (naratriptan HCl) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; Revised October 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=13f4a8ec-75a3-4c51-b3bc-6244f3c79e95&type=display. Accessed February 13, 2024.
 
Arazlo™ (tazarotene) [prescribing information]. Quebec, Canada: Bausch Health Companies Inc. May 2021. Available at: https://www.bauschhealth.com/portals/25/pdf/pi/arazlo-pi.pdf. Accessed February 13, 2024.
 
Aricept® (donepezil) [prescribing information]. Teaneck, NJ: Pfizer, Inc.; November 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=98e451e1-e4d7-4439-a675-c5457ba20975. Accessed February 13, 2024
 
Ativan ® (lorazepam) [prescribing information]. Eatontown, NJ: West-ward Pharmaceuticals; February 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/017794s034s035lbl.pdf. Accessed February 13, 2024.

Atorvaliq® (atorvastatin calcium) [prescribing information]. Farmville, NC: CMP Pharma Inc. Feb 2023. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/213260s000lbl.pdf. Accessed February 13, 2024
 
Auvi-Q™ (epinephrine) [prescribing information]. Bridgewater, NJ. Sanofi-Aventis U.S. LLC. Revised September 2019. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6180fb40-7fca-4602-b3da-ce62b8cd2470&type=display Accessed February 13, 2024.
 
Avita® (tretinoin) [prescribing information]. Research Triangle Park, NC: Bertek Pharmaceuticals, Inc.; July 2018. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=302ca95f-5a7e-4971-870a-5cfea618d7a7 Accessed February 13, 2024.
 
Avodart® (dutasteride) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; January 2020. https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Avodart/pdf/AVODART-PI-PIL.PDF Accessed February 13, 2024.
 
Briviact® (brivaracetam) [prescribing information]. Smyrna, GA: UCB, Inc. March 2022. Available at: https://www.briviact.com/briviact-PI.pdf. Accessed February 13, 2024.
 
butorphanol tartrate [prescribing information]. Toronto, Ontario: Apotex Corp.; August 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b8e48063-0b40-ee43-85c1-4ef2de80c404. Accessed February 13, 2024.
 
Casey, David A., et al. Drugs for Alzheimer's Disease: Are They Effective? U.S. National Library of Medicine, Apr. 2010, www.ncbi.nlm.nih.gov/pmc/articles/PMC2873716/. Accessed February 13, 2024.
 
Caverject® (alprostadil injection) [prescribing information]. New York, NY: Pfizer Inc. December 2017. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a295fc1e-d82c-4f44-bc2d-a552bf594c98. Accessed February 13, 2024.
 
Doxycycline [prescribing information]. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9b52e0a7-f024-4d8a-a59e-374946e60b44. Accessed November 25, 2020. Accessed February 13, 2024.
 
Edex® (alprostadil injection) [prescribing information]. Malvern, PA: Endo Pharmaceuticals, Inc. July 2018. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e8b8ec8d-1318-43e4-a182-446e9f9579de. Accessed February 13, 2024.
 
Entadfi™ (finasteride and tadalafil) [prescribing information]. Miami, FL: ery Inc. December 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=112bf653-8322-4444-8d4d-03234b11c38c. Accessed December 28, 2022.
 
Firvanq® (vancomycin HCL) [prescribing information]. Wilmington, MA: Cutis Pharma; December 2021. Available at: https://firvanq.com/assets/pdf/FIRVANQ-PI-R1.pdf. Accessed February 13, 2024
 
Flolipid® (simvastatin suspension) [prescribing information]. Brooskville, FL: Salerno Pharmaceuticals LP. June 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6ee17d10-6eb1-452a-99e8-02381368b3fe. Accessed February 13, 2024.
 
Furadantin® (nitrofurantoin suspension) [prescribing information]. Parsippany, NJ: Activis Pharma, Inc. December 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d8c5b015-626e-4d57-9b91-392fb53575fa. Accessed February 13, 2024.
 
Hillebrand, G.G., et al. “New Wrinkles on Wrinkling: an 8‐Year Longitudinal Study on the Progression of Expression Lines into Persistent Wrinkles." British Journal of Dermatology, Wiley/Blackwell (10.1111), 22 Feb. 2010, onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2133.2010.09709.x. Accessed February 13, 2024.
 
Hycodan® (hydrocodone bitartrate and homatropine methylpromide) [prescribing information]. Allentown, PA: Genus Lifesciences Inc.; December 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=901d4115-f71a-4681-bd0e-c9b691151b78. Accessed February 13, 2024
 
Imitrex® (sumatriptan succinate) [prescribing information]. Canada: GlaxoSmithKiline LLC. December 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=32f6d89b-4aea-5396-e054-00144ff88e88. Accessed February 13, 2024.
 
Indocin® (indomethacin suspension) [prescribing information]. Wayne, PA: Zyla Life Sciences US Inc. April 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=73878376-1d24-423b-9f37-3666e83c95da. Accessed February 13, 2024
 
Katerzia® (amlodipine suspension) [prescribing information]. Greenwood Village, CO, Silvergate Pharmaceuticals Inc. October 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=df673a4d-acb8-444c-a472-c87ab8cbd366&type=display. Accessed February 13, 2024.
 
Luebberding, Stefanie, et al. Quantification of Age-Related Facial Wrinkles in Men and... : Dermatologic Surgery. Oxford University Press, 2014, journals.lww.com/dermatologicsurgery/pages/articleviewer.aspx?year=2014&issue=01000&article=00003&type=abstract.  February 13, 2024
 
Lyrica® (pregabalin) oral solution [prescribing information]. New York, NJ: Pfizer. June 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=60185c88-ecfd-46f9-adb9-b97c6b00a553.. Accessed February 13, 2024
 
Maxalt® (rizatriptan benzoate) [prescribing information]. Whitehouse Station, NJ: Merck& Co., Inc.; 2012. Revised June 2021.  https://www.merck.com/product/usa/pi_circulars/m/maxalt/maxalt_pi.pdf Accessed February 13, 2024.
 
Meltzer EO, Welch MJ, Ostrom NK. Pill swallowing ability and training in children 6 to 11 years of age. Clin Pediatr. 2006;45:725-33. Accessed February 13, 2024
 
Mestinon® (pyridostigmine bromide) [prescribing information]. Bridgewater, NJ: Bausch Health US, LLC. December 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a851795e-b7a8-40c3-9922-5e79d3eb4d92. Accessed February 13, 2024.
 
Muse® (alprostadil urethral suppository) [prescribing information]. Somerset, NJ: Meda Pharmaceuticals. April 2018. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4c55f3f9-c4cf-11df-851a-0800200c9a66. Accessed July 21, 2021.
 
Namenda® (memantine HCl) [prescribing information]. St. Louis, MO: Forest Laboratories, Inc.; 2012. Revised November 2018.  https://www.allergan.com/assets/pdf/namenda_pi Accessed February 13, 2024.
 
Namzaric™ (Memantine/ donepezil) [prescribing information]. St. Louis, MO: Forest Laboratories, Inc.; January 2019. https://www.allergan.com/assets/pdf/namzaric_pi Accessed February 13, 2024.
 
Naprosyn® (naproxen) [prescribing information]. Athens, GA: Athena Bioscience. August 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f9b4173d-7836-4d7d-b149-1d96f9377ad0. February 13, 2024.
 
Neurontin® (gabapentin) [prescribing information]. New York, NY: Parke-Davis, Division of Pfizer Inc. April 2020. Available at: http://labeling.pfizer.com/ShowLabeling.aspx?id=630. Accessed February 13, 2024.
 
Norliqva® (amlodipine) [prescribing information]. Farmville, NC: CMP Pharma Inc; February 2022. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c1730a51-4383-4c61-a9a1-7e1326bd0abe. Accessed February 13, 2024.
 
Nortriptyline [prescribing information]. Greensville, SC: Pharmaceutical Associates, Inc. February 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3fcabf90-357a-4a06-b680-9572dc28bcfe. Accessed February 13, 2024.
 
Nurtec® ODT (rimegepant) [prescribing information]. New Haven, CT: Biohaven Pharmaceuticals, Inc.; April 2022. Available from: https://www.nurtec.com/pi. Accessed February 13, 2024.
 
Onfi® (clobazam) [prescribing information]. Winchester, KY: Catalent Pharma Solutions, LLC. February 2021. Available at: https://www.lundbeck.com/upload/us/files/pdf/Products/ONFI_PI_US_EN.pdf. Accessed February 13, 2024.
 
Oxazepam [prescribing information]. Princeton, NJ: Sandoz Inc.; 2011. Revised February 2021. Accessed February 13, 2024.
 
Proscar® (finasteride) [prescribing information]. Whitehouse Station, NJ: Merck & Co., Inc.; June 2021.  Accessed February 13, 2024.
 
“Prostate Enlargement (Benign Prostatic Hyperplasia)." National Institute of Diabetes and Digestive and Kidney Diseases, U.S. Department of Health and Human Services, 1 Sept. 2014, www.niddk.nih.gov/health-information/urologic-diseases/prostate-problems/prostate-enlargement-benign-prostatic-hyperplasia.
 
Prozac® (fluoxetine) oral solution [prescribing information]. Greenville, SC: Pharmaceutical Associates, Inc. December 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=180a07fd-1f6a-4617-b8e0-f938c65ba273. Accessed February 13, 2024.
 
Qbrelis® (lisinopril) [prescribing information]. Greenwood Village, CO: Silvergate Pharmaceuticals; July 2020. Available from: https://qbrelis.com/Qbrelis-Prescribing-Info.pdf. Accessed February 13, 2024.
 
Qdolo™ (tramadol) [prescribing information]. Athens, GA: Athena Bioscience, LLC. September 2020. Available at: https://qdolo.com/wp-content/uploads/2020/10/QDOLO-Prescribing-Information.pdf. Accessed February 13, 2024.
 
Qiu, Chengxuan, et al. Epidemiology of Alzheimer's Disease: Occurrence, Determinants, and Strategies toward Intervention. U.S. National Library of Medicine, June 2009, www.ncbi.nlm.nih.gov/pmc/articles/PMC3181909/. Accessed February 13, 2024.
 
Razadyne ER ® (galantamine) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2016. Revised October 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021169s033,021615s024lbl.pdf. Accessed February 13, 2024.
 
Relenza® (zanamivir) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; 2012. Revised October 2021. https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Relenza/pdf/RELENZA-PI-PIL-COMBINED.PDF. Accessed February 13, 2024.
 
Relpax® (eletriptan) [prescribing information]. New York, NY: Roerig (Pfizer Inc.); 2012. Revised March 2020. http://labeling.pfizer.com/ShowLabeling.aspx?id=621 Accessed February 13, 2024.
 
Restoril™ (Temazepam) [prescribing information]. Webster Groves, MO: Mallinckrodt; 2016. Revised February 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018163s065lbl.pdf. Accessed February 13, 2024.
 
Retin-A® (tretinoin) [prescribing information]. Bridgewater, NJ: Valeant Pharmaceuticals North America; 2016. Revised September 2019. Accessed February 13, 2024.
 
Retin-A Micro® (tretinoin) [prescribing information].  Bridgewater, NJ: Valeant Pharmaceuticals North America; 2016. Revised October 2017. Accessed February 13, 2024.
 
Reyvow® (lasmiditan) [prescribing information]. Indianapolis, IN: Lilly USA, LLC; September 2022. Available from: http://pi.lilly.com/us/reyvow-uspi.pdf. Accessed February 13, 2024.
 
Riomet® (metformin hydrochloride) oral solution [prescribing information]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; November 2018. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021591s007lbl.pdf. Accessed February 13, 2024.
 
Riomet ER™ (metformin hydrochloride for extended-release oral suspension) [prescribing information]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; August 2019. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212595s000lbl.pdf. Accessed February 13, 2024.
 
Tegretol® (carbamazepine) [prescribing information]. East Hanover, NJ: Norvatis Pharmaceuticals Corporations. March 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8d409411-aa9f-4f3a-a52c-fbcb0c3ec053. Accessed  February 13, 2024
 
Thyquidity™ (levothyroxine sodium) oral solution [prescribing information]. Largo, FL: Vertice Specialty Group. December 2020. Available at: https://www.thyquidity.com/pdf/Prescribing-Information.pdf. Accessed February 13, 2024
 
Tosymra (sumatriptan) nasal spray [prescribing information]. Maple Grove, MN: Upsher-Smith Laboratories, LLC. February 2021. Available from: www.upsher-smith.com/wp-content/uploads/TOS-MI.pdf. Accessed February 13, 2024.
 
Tranxene® (clorazepate) [prescribing information]. Lebanon, NJ: AbbVie LTD; May 2018. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/017105s079lbl.pdf. Accessed February 13, 2024.
 
Treximet® (sumatriptan/naproxen) [prescribing information]. Morristown, NJ. Pernix Therapeutics. April 2021. http://www.treximet.com/Areas/Patient/Contents/pdf/prescribing-information.pdf Accessed February 13, 2024
 
Trileptal® (oxcarbazepine) oral suspension. [prescribing information] East Hanover, NJ: Norvatis. May 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4c5c86c8-ab7f-4fcf-bc1b-5a0b1fd0691b. Accessed February 13, 2024.
 
Twyneo® (Tretinoin-benzoyl peroxide) [prescribing information]. Fort Worth, TX: Galderma Laboratories, L.P. July 2021. Available from: https://www.galderma.com/us/sites/default/files/2022-02/Twyneo_PI.pdf. Accessed February 13, 2024.
 
Ubrelvy® (ubrogepant) [prescribing information]. Madison, NJ: Allergan USA, Inc; March 2021. https://media.allergan.com/products/Ubrelvy_pi.pdf. Accessed February 13, 2024
 
Ultracet® (tramadol/acetaminophen) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; April 2022. http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/ULTRACET-pi.pdf. Accessed February 13, 2024
 
Ultram® (tramadol) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; October 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021692s015lbl.pdf Accessed February 13, 2024
 
Ultram® ER (tramadol ER) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; September 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021692s015lbl.pdf. Accessed February 13, 2024.
 
Valganciclovir (Valcyte) [prescribing information]. San Francisco, CA: Genetech USA, inc. December 2021. VALCYTE Prescribing Information (gene.com). Accessed November 4, 2022. 
 
Xanax® (alprazolam) [prescribing information]. New York, NY: Pharmacia & Upjohn Company; March 2021. http://labeling.pfizer.com/ShowLabeling.aspx?id=547 Accessed February 13, 2024.
 
Xatmep™ (methotrexate) [prescribing information]. Greenwood Village, CO: Silvergate Pharmaceuticals, Inc.; September 2020. https://xatmep.com/Xatmep-Prescribing-Info.pdf. Accessed February 13, 2024.
 
Zavzpret™ (zavegepant) [package insert]. New York, NY: Pfizer Inc. March 2023. Available from: https://labeling.pfizer.com/ShowLabeling.aspx?id=19471. Accessed February 13, 2024
 
Ziana® (tretinoin/clindamycin) [prescribing information]. Brigewater, NJ: Medicis Pharmaceutical Corp; Revised March 2017. Accessed February 13, 2024.
 
Zomig® (zolmitriptan) [prescribing information]. Macclesfield, Cheshire UK: AstraZeneca Pharmaceuticals; 2012. Revised May 2019.  Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=84b51cb9-83f3-4a49-7fa3-1adc0f963658&type=display. Accessed February 13, 2024.
 
Zomig NS® (zolmitriptan nasal) [prescribing information]. Macclesfield, Cheshire UK: AstraZeneca Pharmaceuticals; 2012. Revised April 2019. https://www.azpicentral.com/zomig_nasal/zomig_nasal.pdf#page=1. Accessed February 13, 2024.
 
Zyflo CR® (Zileuton) [prescribing information]. Cary, NC: Chiesi USA, Inc., Revised December 2018. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022052s014lbl.pdf. Accessed February 13, 2024.
3612/18/202312/18/20244/1/2024 1:22 AMNo presence informationsrv_ppsgw_P

Rx.01.33 Off Label Use

Rx.01.17 Cosmetic Policy

Rx.01.251 Migraine and Headache agents

Rx.01.197 Opioid Policy

Rx.01.202 Prior authorization requirements for select drugs

Rx.01.33 Off-Label Use

Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit​



Drug NameAge Edit:  Prior Authorization Required (years)
Acne Medications​
Tretinoin, topical (e.g., Atralin, Avita, Retin-A, Retin-A micro, Altreno, etc.)Age 26 and over
Adapalene (Differin)Age 26 and over
Adapalene/ Benzoyl Peroxide (Epiduo)Age 26 and over
Tretinoin/ clindamycin (Ziana)Age 26 and over
Dapsone (Aczone) 5%Under age 12
Dapsone (Aczone) 7.5%Under age 9
Triafarotene (Aklief)Age 26 and over
Tazarotene (Fabior, Arazlo, Tazorac)Age 26 and over
Tretinoin-benzoyl peroxide (Twyneo)Age 26 and over
Alzheimer's Drugs​
Donepezil (Aricept [ODT]), AdlarityUnder age 50
Rivastigmine (Exelon)Under age 50
Memantine (Namenda [XR])Under age 50
Galantamine (Razadyne [ER])Under age 50
Memantine/ donepezil (Namzaric)Under age 50
Anticonvulsant Agents​
Clobazam (Onfi) suspension Age 13 and over
Rufinamide (Banzel) suspension Age 13 and over
Carbamazepine (Tegretol) suspension Age 13 and over
Gabapentin (Neurontin) Oral solution Age 13 and over
Brivaracetam (Briviact) oral solution Age 13 and over
Pregabalin solution (Lyrica®)Age 13 and over
Oxcarbazepine suspension (Trileptal®)Age 13 and over
Antidepressants​
Nortriptyline solutionAge 13 and over
Fluoxetine solution (Prozac)Age 13 and over
Antidiabetic Agents​
Metformin (Riomet) ER solutionAge 13 and over
Metformin (Riomet) suspension                                      Age 13 and over
Acute migraine Agents​
Eletriptan (Relpax)Under age 18
Sumatriptan (Imitrex, Onzetra. Xsail, Zembrace Symtouch, Tosymra)Under age 18
Butorphanol tartrate NSUnder age 18
Naratriptan (Amerge)Under age 18
Rizatriptan (Maxalt/ Maxalt MLT)Under age 6
Zolmitriptan (Zomig/Zomig ZMT)Under age 12
Almotriptan    Under age 12
Frovatriptan (Frova)Under age 18
Sumatriptan/naproxen (Treximet)Under age 12
TosymraUnder age 18
Lasmiditan (Reyvow)Under age 18
Ubrogepan (Ubrelvy)Under age 18
Rimegepant (Nurtec ODT)Under age 18
Zavegepant (Zayzpret)Under age 18
Antihypertensives​
Amlodipine (Katerzia, Norliqva)Age 13 and over
Enalapril (Epaned)Age 13 and over
Lisinopril (Qbrelis)Age 13 and over
Valsartan oral solutionAge 13 and over
Anti-Infectives​
Vancomycin oral solution (Firvanq)Age 13 and over
Zanamivir (Relenza)Under age 5
Nitrofurantoin suspension (Furdantin)Age 13 and over
Doxycycline hyclate DR 75mg, 150mg (Doryx 75mg, 150mg), Doxycycline hyclate 75mg, 150mg (Acticlate 75mg, 150mg), Doxycycline monohydrate /Mondoxyn NL 75mg capsule (Monodox 75mg), Doxycycline monohydrate 150mg capsule and tablet (Adoxa 150mg)Age 18 and over
Valganciclovir oral solution (Valcyte)Age 13 and over
Benign Prostate Hypertrophy​
Dutasteride (Avodart)Under age 50
Finasteride (Proscar)Under age 50
Finasteride-Tadalafil (Entadfi)Under age 50
Erectile Dysfunction Agents​
Alprostadil (Muse®, Edex®, Caverject®, IFE-PG20)Under age 55
Benzodiazepines​
FlurazepamUnder age 15
Triazolam (Halcion)Under age 18
Quazepam (Doral)Under age 18
EstazolamUnder age 18
Temazepam (Restoril)Under age 18
Lorazepam (Ativan)Under age 12
ChlordiazepoxideUnder age 6
OxazepamUnder age12
Clorazepate (Tranxene)Under age 9
Alprazolam (Xanax) Under age 18
Leukotriene Inhibitors​
Zafirlukast (Accolate)Under age 5
Zileuton (Zyflo [CR])Under age 12
Pain​

Tramadol/Tramadol ER containing products

(e.g., Ultram, Ultram ER, Ultracet, Conzip) 

Under age 12
Tramadol solution (Qdolo)Under age 18
Codeine containing productsUnder age 12
Indomethacin (Indocin) suspensionAge 13 and over
Naproxen (Naprosyn) suspensionAge 13 and over
Cough/Cold Products​
Codeine and hydrocodone containing productsUnder age 18
Miscellaneous​
Auvi-Q 0.1mgAge 4 and over
Xatmep (Methotrexate solution)      Age 13 and over
Pyridostigmine (Mestinon) solutionAge 13 and over
Thyquidity solutionAge 13 and over
Simvastatin (Flolipid) suspensionAge 13 and over
Atorvastatin calcium suspension (Atorvaliq)Age 13 and over

 



medications that have age edits medications that have age edits
338
  
4/1/2024Rx.01.259CommercialOyenusi, OluwadamilolaQ4-2023

The antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). These vasculitis are complex, immune-mediated disorders in which tissue injury results from the interplay of an initiating inflammatory event and a highly specific immune response. Part of this response is directed against previously shielded epitopes of neutrophil granule proteins, leading to high-titer autoantibodies known as ANCA. The production of ANCA is one of the hallmarks of the ANCA-associated vasculitis. ANCA are directed against antigens present primarily within the granules of neutrophils and monocytes; these autoantibodies produce tissue damage via interactions with primed neutrophils and endothelial cells.

Avacopan (Tavneos™) is indicated as an adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. Avacopan does not eliminate glucocorticoid use.

Avacopan is a complement 5a receptor (C5aR) antagonist that inhibits the interaction between C5aR and the anaphylatoxin C5a. Avacopan blocks C5a-mediated neutrophil activation and migration. The precise mechanism by which avacopan exerts a therapeutic effect in patients with ANCA-associated vasculitis has not been definitively established.



The intent of this policy is to communicate the medical necessity criteria for Avacopan (Tavneos™) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA: Avacopan (Tavneos™) is approved when ALL of the following are met:

  1. Diagnosis of one of the following types of severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis:
    1. Granulomatosis with polyangiitis (GPA); or
    2. Microscopic polyangiitis (MPA); and
  2. Member is receiving concurrent immunosuppressant therapy with one of the following:
    1. Cyclophosphamide; or
    2. Rituximab; and
  3. One of the following:
    1. Member is concurrently on glucocorticoids (e.g., prednisone); or
    2. Inadequate response or inability to tolerate glucocorticoids (e.g., prednisone); and
  4. Member is 18 years of age or older; and
  5. Prescribed by or in consultation with one of the following:
    1. Nephrologist; or
    2. Pulmonologist; or
    3. Rheumatologist


Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Avacopan (Tavneos™) is re-approved when ALL of the following are met:

  1. Member does not show evidence of progressive disease while on therapy; and
  2. Member is receiving concurrent immunosuppressant therapy (e.g., azathioprine, cyclophosphamide, methotrexate, rituximab); and
  3. Prescribed by or in consultation with one of the following:
    1. Nephrologist; or
    2. Pulmonologist; or
    3. Rheumatologist


Reauthorization duration: 2 years
 


None

Pathogenesis of antineutrophil cytoplasmic autoantibody-associated vasculitis. UpToDate. October 2020. Available at: https://www.uptodate.com/contents/pathogenesis-of-antineutrophil-cytoplasmic-autoantibody-associated-vasculitis?search=antineutrophil%20cytoplasmic%20autoantibody%20associated%20vasculitis&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1. Accessed February 13, 2024

Tavneos (avacopan) [package insert]. Cincinnati, OH. ChemoCentryx, Inc. Feburary 2022. Available at:

https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=7ea3c60a-45c7-44cc-afc2-d87fa53993c0&type=display. Accessed February 13, 2024


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​Rx.01.33 Off Label Use
Tavneos™Avacopan
339
  
4/1/2024Rx.01.171CommercialOyenusi, OluwadamilolaQ4-2023

Bile acid synthesis disorders (BASD) are extremely rare, genetic, metabolic conditions that exhibit manifestations of liver disease, steatorrhea, and complications from decreased fat soluble vitamin absorption.  Individuals with BASD lack the enzymes needed to synthesize cholic acid.  If untreated, these individuals fail to grow and can develop life-threatening liver injury. 

Cholic acid is a primary bile acid synthesized from cholesterol in the liver. In bile acid synthesis disorders due to single enzyme deficiencies (SEDs) in the biosynthetic pathway, and in peroxisomal disorders (PDs) including Zellweger spectrum disorders, deficiency of primary bile acids leads to unregulated accumulation of intermediate bile acids and cholestasis. Bile acids facilitate fat digestion and absorption by forming mixed micelles, and facilitate absorption of fat-soluble vitamins in the intestine.

Endogenous bile acids, including cholic acid, enhance bile flow and provide the physiologic feedback inhibition of bile acid synthesis. The mechanism of action of cholic acid has not been fully established; however, it is known that cholic acid and its conjugates are endogenous ligands of the nuclear receptor, farnesoid X receptor (FXR). FXR regulates enzymes and transporters that are involved in bile acid synthesis and in the enterohepatic circulation to maintain bile acid homeostasis under normal physiologic conditions.

Cholic acid (Cholbam®) is indicated for:

  1. The treatment of BASD due to SEDs
  2. Adjunctive treatment of PDs including Zellweger spectrum disorders, in patients who exhibit manifestations of liver disease, steatorrhea or complications from decreased fat soluble vitamin absorption.​

Treatment with cholic acid (Cholbam®) is approved for children aged 3 weeks and older, and adults.


The intent of this policy is to communicate the medical necessity criteria for cholic acid (Cholbam®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA Cholic acid (Cholbam®) is approved when ALL of the following are met:

  1. One of the following:
    1. Treatment of bile acid synthesis disorder due to single enzyme defect; or
    2. Adjunctive treatment of peroxisomal disorder including Zellweger spectrum disorder in patients who exhibit manifestations of liver disease, steatorrhea, or complications from decreased fat soluble vitamin absorption; and
  2. Prescribed by or in consultation with one of the following:
    1. hepatologist; or
    2. gastroenterologist; or
    3. medical geneticist; or
    4. other specialist that treats inborn errors of metabolism; and
  3. No documentation of extrahepatic manifestations of bile acid synthesis disorders due to single enzyme defects or peroxisomal disorders including Zellweger spectrum disorder

 

Initial authorization duration: 3 months

 

REAUTHORIZATION CRITERIA Cholic acid (Cholbam®) is re-approved when there is documentation of improved liver function tests (e.g., aspartate aminotransferase [AST], alanine aminotransferase [ALT]) from the start of treatment.

 

Reauthorization duration: 2 years


None
Cholbam® (Cholic acid) [package insert]. Baltimore MD. Asklepion Pharmaceuticals, LLC. May 2021. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205750s000lbl.pdf. Accessed February 13, 2024

Cholic acid. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, CO.  Available from: http://www.micromedexsolutions.com. Accessed February 13, 2024

1012/18/202312/18/20244/1/2024 1:23 AMNo presence informationsrv_ppsgw_P
Rx.01.33 Off-Label Use 
Cholbam®cholic acid
340
  
4/1/2024Rx.01.136CommercialOyenusi, OluwadamilolaQ4-2023

Cystinosis is a rare, genetic disorder in which the amnio acid cystine accumulates in tissues and organs, most commonly the kidneys and eyes.  Treatment with cysteamine should be initiated as soon as the diagnosis is made to preserve kidney function, prevent hypothyroidism, and improve growth in affected children.  Orally administered cysteamine does not reach the cornea, thus ophthalmic administration is necessary for accumulation of corneal cystine crystals.

Cysteamine acts as a cystine-depleting agent by converting cystine to cysteine and cysteine-cysteamine mixed disulfides.  The result is a reduction in cystine crystals.

Cysteamine hydrochloride (Cystaran®/Cystadrops®) is indicated for the treatment of corneal cystine crystal accumulation in adults and children with cystinosis. 

Cysteamine bitartrate (Cystagon®/Procysbi®) is indicated for the treatment of nephropathic cystinosis in adult and children.


The intent of this policy is to communicate the medical necessity criteria for cysteamine Hydrochloride (Cystaran®/Cystadrops®) and cysteamine bitartrate (Cystagon®/ Procysbi®) as provided under the member's prescription drug benefit.

Cystinosis
 
INITIAL CRITERIA: Cysteamine hydrochloride (Cystaran®/Cystadrops®) Ophthalmic Solution is approved when BOTH of the following are met:

  1. Diagnosis of cystinosis; and
  2. Member has corneal cystine crystal accumulation; and
  3. Prescribed by or in consultation with an ophthalmologist or a specialist with experience in treating cystinosis with corneal cystine crystal accumulation

 

Initial authorization duration: 2 years

 
REAUTHORIZATION CRITERIA Cysteamine hydrochloride (Cystaran®, Cystadrops®) is re-approved when there is documentation of positive clinical response to therapy.
 

Reauthorization duration: 2 years 
___________________________________________________________________________________________

Nephrotic Cystinosis
 
INITIAL CRITERIA: Cysteamine bitartrate (Cystagon®) is approved when there is a diagnosis of nephrotic cystinosis.

Initial authorization: 2 years

REAUTHORIZATION CRITERIA Cysteamine bitartrate (Cystagon®) is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years

INITIAL CRITERIA: Cysteamine bitartrate (Procysbi®) is approved when ALL of the following are met:

  1. Diagnosis of nephrotic cystinosis; and
  2. Member is 1 year of age or older; and
  3. Inadequate response or titration from cysteamine bitartrate immediate release capsules (Cystagon®)

 
Initial Authorization duration: 2 years

 
REAUTHORIZATION CRITERIA: Cysteamine bitartrate (Procysbi®) is re-approved when there is documentation of positive clinical response to therapy.
 

Reauthorization duration: 2 years

 


None

Cystadrops® [package insert] Lebanon, NJ. Recordati Rare Diseases Inc. August 2020. Available from: https://www.cystadrops.com/wp-content/uploads/cystadrops-prescribing-information.pdf. Accessed February 13, 2024.

Cystagon® [package insert]. Morgantown WV. Mylan Pharmaceuticals Inc. August 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/020392s010lbl.pdf. Accessed December 28,, 2022.

Cystanosis. National Organization for Rare Disorders. Available at: http://rarediseases.org/rare-diseases/cystinosis/. Accessed February 13, 2024.

Cystaran® [package insert]. Amityville NY. Sigma-Tau Pharmaceuticals, Inc. February 2022. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/200740s000lbl.pdf.  Accessed February 13, 2024.

Niaudet P. Cystinosis. UpToDate. February 2020. Available at: https://www.uptodate.com/contents/cystinosis?source=search_result&search=cystinosis&selectedTitle=1~31. Accessed February 13, 2024.

Procysbi® [package insert]. Novato CA. Raptor Pharmaceuticals Inc. February 2022. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203389s010lbl.pdf. Accessed February 13, 2024.


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Rx. 01.33 Off-Label Use 
Rx.01.76 ​Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit 
Brand NameGeneric Name
Cystagon®Cysteamine Bitartrate
Cystaran®/Cystadrops®Cysteamine Hydrochloride
Procysbi®Cysteamine Bitartrate

Cystaran®/Cystadrops®, Cystagon®/ Procysbi®cysteamine Hydrochloride, cysteamine bitartrate
341
  
4/1/2024Rx.04.9Claim Payment PolicyOyenusi, OluwadamilolaQ4-2023
​A cosmetic drug is intended to be used for cleansing, beautifying, promoting attractiveness, or altering the appearance of human body from which no significant improvement in physiologic function can be expected. 
The intent of this policy is to communicate the coverage of cosmetic drugs under the member’s prescription drug benefit.

Coverage is subject to the terms, conditions, and limitations of the member's contract.
Cosmetic drugs, or drugs prescribed for cosmetic purposes, are not covered under the pharmacy benefit. Cosmetic drugs or drugs prescribed for cosmetic purposes are:

  • Used for other than the treatment of illness, injuries, congenital birth defect or restoration of physiological function; and
  • Used for cleansing, beautifying, promoting attractiveness or altering the appearance of any part of the human body


 
Examples of drugs prescribed for cosmetic use include, but are not limited to:

Brand Name         Generic Name   FDA Indication     
EgriftaTesamorelinReduction of excess abdominal fat in HIV-infected patients with lipodystrophy.
Renova, Refissa (branded product only)TretinoinAdjunctive agent for use in the mitigation (palliation) of fine wrinkles, mottled hyperpigmentation, and tactile roughness of facial skin in patients who do not achieve such palliation using comprehensive skin care and sun avoidance programs alone
Propecia 1mgFinasteride 1mgMale pattern alopecia
Multiple (e.g., Lustra)HydroquinoneDiscoloration of skin; Hyperpigmentation of skin
Latisse 0.03% solutionBimatoprostHypotrichosis of the eyelashes
Vaniqa 13.9% creamEflornithineReduction of unwanted facial hair in women
Multiple (e.g., Rogaine)Minoxidil topicalMale pattern alopecia; hair regrowth in women

N/A
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Rx.01.2 Applicable Age Edits 

Rx.01.33 Off-Label Use 

Rx.01.202 Prior Authorization Requirements for Select Drugs 

12.01.03a​ Cosmetic Procedure medical policy 


cosmetic drugscosmetic drugs
342
  
4/1/2024Rx.01.24CommercialOyenusi, OluwadamilolaQ4-2023

Pseudobulbar affect (PBA) is a disinhibition syndrome characterized by uncontrolled laughing or crying disproportionate or inappropriate to the social context.  The pathophysiology of PBA is not completely understood, but is thought to involve disruption of serotonin and glutamate pathways. PBA is associated with a variety of neurological disorders including amyotrophic lateral sclerosis, extrapyramidal and cerebellar disorders, multiple sclerosis, traumatic brain injury, Alzheimer's dementia, stroke, and brain tumors. Estimates of the prevalence of PBA vary widely, from 5% to over 50% depending on the patient population studied. 

The goal of treating PBA is to diminish the frequency and severity of episodes.  Treatment options include antidepressants, specifically selective serotonin reuptake inhibitors, tricyclic antidepressants, and dextromethorphan hydrobromide and quinidine sulfate.

Dextromethorphan hydrobromide and quinidine sulfate (Nuedexta®) is the first medications indicated for the treatment of PBA.  Dextromethorphan hydrobromide (DM) and quinidine sulfate (Nuedexta®) is a combination of existing products, dextromethorphan and quinidine. DM is a sigma-1 receptor agonist and an uncompetitive NMDA receptor antagonist. Quinidine increases plasma levels of dextromethorphan by competitively inhibiting cytochrome P450 2D6, which catalyzes a major biotransformation pathway for dextromethorphan. The mechanism by which dextromethorphan exerts therapeutic effects in patients with pseudobulbar affect is unknown.

 



The intent of this policy is to communicate the medical necessity criteria for dextromethorphan hydrobromide and Quinidine sulfate (Nuedexta®) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA: Dextromethorphan hydrobromide and quinidine sulfate (Nuedexta®) is approved when ALL of the following are met:

  1. Diagnosis of pseudobulbar affect; and
  2. Prescribed by or in consultation with a neurologist or psychiatrist; and
  3. Member is 18 years of age or older; and
  4. There is an absence of cardiac rhythm disorder documented by a cardiac test (e.g., electrocardiogram); and
  5.  Member has one of the following conditions:
    1. Amyotrophic lateral sclerosis
    2. Multiple sclerosis
    3. Alzheimer's disease
    4. Parkinson's disease
    5. Stroke
    6. Traumatic brain injury

Initial authorization duration: 6 months


REAUTHORIZATION CRITERIA: Dextromethorphan hydrobromide and quinidine sulfate (Nuedexta®) is re-approved when both of the following are met:

  1. Documentation of clinical benefit from ongoing therapy (e.g., decrease in laughing/crying episodes); and
  2. Prescribed by or in consultation with a neurologist or psychiatrist

Reauthorization duration: 2 years


None

Ahmed A, Simmons Z. Pseudobulbar affect: prevalence and management. Therapeutics and Clinical Risk Management. 2013;9:483-9.  Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849173/pdf/tcrm-9-483.pdf. Accessed February 13, 2024

Nuedexta [package insert]. Aliso Viejo CA. Avanir Pharmaceuticals, Inc. June 2019. Available at: https://www.nuedexta.com/sites/default/files/Prescribing_Information.pdf. Accessed February 13, 2024




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Rx.01.33 Off-Label Use 
Nuedexta®dextromethorphan hydrobromide and Quinidine sulfate
343
  
4/1/2024Rx.01.204CommercialOyenusi, OluwadamilolaQ4-2023

Rosacea is a common, chronic skin disorder that has a multitude of clinical manifestations primarily located on the central face. Adults over the age of 30 are most commonly affected, and women are more commonly affected than men. The pathophysiology of rosacea is not well understood, but possible etiologies include: abnormalities in innate immunity; inflammatory reactions to cutaneous microorganisms; ultraviolet damage; and vascular dysfunction. There are four main subtypes of rosacea, including papulopustular rosacea. Papulopustular rosacea is characterized by acne-like inflammatory papules and pustules typically located on the central face. Unlike acne, comedones do not occur in rosacea; in addition, inflammation may extend outward beyond the follicular unit to form plaques.

Doxycycline IR/ER (Oracea) is indicated for the treatment of only inflammatory lesions (papules and pustules) of rosacea in adults. No meaningful effect was demonstrated for generalized erythema (redness) of rosacea.

Doxycycline, a member of the tetracycline class of antibiotics, exerts its therapeutic effect at antimicrobial doses by inhibiting bacterial protein synthesis. When used at sub-antimicrobial doses, doxycycline produces an anti-inflammatory effect which is believed to assist in the treatment of rosacea. 
​The intent of this policy is to communicate the medical necessity criteria for doxycycline IR/ER (Oracea) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA: Doxycycline IR/ER (Oracea) is approved when ALL of the following are met:

  1. Diagnosis of inflammatory lesions (papules and pustules) rosacea; and
  2. Patient is 18 years of age or older; and
  3. Inadequate response or inability to tolerate generic doxycycline IR 20mg tablets

Initial authorization duration: 9 months

REAUTHORIZATION CRITERIA: Doxycycline IR/ER (Oracea) is re-approved when BOTH of the following are met:

  1. Documentation of positive clinical response to therapy; and
  2. Documentation of continued need for treatment beyond 9 months

Reauthorization duration: 2 years


None

Rosacea: Pathogenesis, clinical features and diagnosis. UpToDate. https://www.uptodate.com/contents/rosacea-pathogenesis-clinical-features-and-diagnosis. Updated March 17, 2022. Accessed February 13, 2024

Oracea® (doxycycline) [package insert]. Fort Worth, TX: Galderma Laboratories; December 2021.  Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=aa15c93a-ff4c-447a-8a21-96da506d8997&type=display. Accessed February 13, 2024

Doxycycline. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at http://online.lexi.com. Accessed February 13, 2024

Rosacea. L Diagnosis and Treatment. American Family Physician Website. http://www.aafp.org/afp/2015/0801/p187.html. Published August 1, 2015. Accessed February 13, 2024


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Rx.01.33 Off-Label Use
Oraceadoxycycline IR/ER
344
  
4/1/2024Rx.01.188CommercialOyenusi, OluwadamilolaQ4-2023

Nausea and vomiting of pregnancy is a common condition affecting approximately 50-80% of pregnancies.  The etiology of nausea and vomiting in pregnancy is unknown, but various theories exist including psychologic predisposition, evolutionary adaption, and hormonal stimulus.  While mortality from nausea and vomiting of pregnancy is rare, significant morbidity, including hospital admissions, has been observed.

Initiating prenatal vitamins three months prior to conception may reduce the incidence and severity of nausea and vomiting of pregnancy.  Treatment with pyridoxine or pyridoxine and doxylamine is effective and considered first line pharmacologic therapy. Ginger and acupressure have also shown beneficial effects in the treatment of nausea and vomiting of pregnancy.

Doxylamine/ pyridoxine (Diclegis®, Bonjesta®) is a fixed dose combination drug product of doxylamine succinate (an antihistamine) and pyridoxine hydrochloride (a vitamin B6 analog), indicated for the treatment of nausea and vomiting of pregnancy in women who do not respond to conservative management.  The mechanism of action of doxylamine/ pyridoxine for the treatment of nausea and vomiting of pregnancy is unknown. Diclegis® contains 10mg doxylamine and 10mg pyridoxine.  Bonjesta® contains 20mg doxylamine and 20mg pyridoxine. 


The intent of this policy is to communicate the medical necessity criteria for doxylamine/ pyridoxine (Diclegis®, Bonjesta®) as provided under the member's prescription drug benefit.

Doxylamine/pyridoxine (Diclegis®, Bonjesta®) is approved when ALL of the following are met:

  1. Diagnosis of nausea and vomiting of pregnancy; and
  2. Inadequate response to conservative management (e.g., change in dietary habits, ginger, acupressure, etc.); and
  3. Inadequate response or inability to tolerate generic doxylamine and generic pyridoxine (Vitamin B6) taken together.
     

Authorization duration: 9 months


None

Bonjesta (doxylamine/pyridoxine) [package insert]. Bryn Mawr, PA. Duchesnay USA, Inc. June 2018. Available at: https://files.duchesnay.com/duchesnay-usa/bonjesta/bonjesta-prescribing-information.pdf. Accessed February 13, 2024.

Diclegis (doxylamine/ pyridoxine) [package insert]. Bryn Mawr, PA. Duchesnay USA, Inc. October 2022. Available at: https://files.duchesnay.com/duchesnay-usa/diclegis/diclegis-prescribing-information.pdf. Accessed February 13, 2024.

The American College of Obstetricians and Gynecologists. Practice Bulleting No. 153: Nausea and Vomiting of Pregnancy. Obstet Gynecol. 2015;126:e12-24.


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Rx.01.33 Off-Label Use 
Brand nameGeneric name
Diclegisdoxylamine/ pyridoxine
Bonjestadoxylamine/ pyridoxine

Diclegis®, Bonjesta®doxylamine/ pyridoxine
345
  
4/1/2024Rx.01.236CommercialOyenusi, OluwadamilolaQ4-2023

Uterine fibroids, or leiomyomas, and benign neoplasms commonly found in women of reproductive age. Fibroids produce endogenous aromatase, allowing for production of estradiol. This facilitates the growth of fibroids in women. One of the most common symptoms of uterine fibroids is abnormal, usually excessive, menstrual bleeding. Treatment of fibroids usually consists of symptom management and preservation of fertility (if desired). 

Oriahnn® (elagolix, estradiol, and norethindrone acetate) is a combination product containing elagolix (a gonadotropin-releasing hormone antagonist), estradiol (an estrogen), and norethindrone acetate (a progestin), indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women.

Therapy with Oriahnn® (elagolix, estradiol, and norethindrone acetate) should be limited to 24 months due to the risk of continued bone loss, which may not be reversible.

Myfembree® (relugolix, estradiol and norethindrone acetate) is a combination product of relugolix (a non-peptide GnRH receptor antagonist), estradiol (an estrogen), and norethindrone acetate (a progestin), indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women and management of moderate to severe pain associated with endometriosis.

Use of Myfembree® (relugolix, estradiol and norethindrone acetate) should be limited to 24 months due to the risk of continued bone loss which may not be reversible


The intent of this policy is to communicate the medical necessity criteria for Oriahnn® (elagolix, estradiol, and norethindrone acetate) and Myfembree® (relugolix, estradiol and norethindrone acetate) as provided under the member's prescription drug benefit.


 
Heavy Menstrual Bleeding Associated with Uterine Leiomyomas
INITIAL CRITERIA: Elagolix/estradiol/norethindrone acetate (Oriahnn®) or Relugolix/estradiol/norethindrone acetate (Myfembree®) is approved when ALL of the following are met:

  1. Diagnosis of heavy menstrual bleeding associated with uterine leiomyomas (fibroids); and
  2. Member is premenopausal; and
  3. One of the following:
    1. Inadequate response after at least 3 months OR inability to tolerate ONE of the following:
      1. Combination (estrogen/progestin) contraceptive; or
      2. Progestins; or
    1. Member has had a previous interventional therapy to reduce bleeding (e.g., uterine-artery embolization and magnetic resonance-guided focused ultrasonography); and
  1. Treatment duration has not exceeded a total of 24 months

 

Initial authorization duration: 12 months

REAUTHORIZATION CRITERIA: Elagolix/estradiol/norethindrone acetate (Oriahnn®) or Relugolix/estradiol/norethindrone acetate (Myfembree®) is re-approved when BOTH of the following are met:

  1. Member has improvement in bleeding associated with uterine leiomyomas (fibroids) (e.g., significant/sustained reduction in menstrual blood loss per cycle, improved quality of life, etc.); and
  2. Treatment duration has not exceeded a total of 24 months

 

Reauthorization duration: 12 months

__________________________________________________________________________________________
Pain Associated with Endometriosis

INITIAL CRITERIA: Relugolix/estradiol/norethindrone acetate (Myfembree®) is approved when ALL of the following are met:

  1. Diagnosis of moderate to severe pain associated with endometriosis; and
  2. Member is premenopausal; and
  3. One of the following:
    1. Inadequate response after at least 3 months or inability to tolerate one of the following:
      1. Danazol; and
      2. Combination (estrogen/progestin) contraceptive; and
      3. Progestins; or
    1. Member has had surgical ablation to prevent recurrence; and
  1. Treatment duration has not exceeded a total of 24 months

 
Initial authorization duration: 12 months


REAUTHORIZATION CRITERIA: Relugolix/estradiol/norethindrone acetate (Myfembree®) is re-approved when BOTH of the following are met:

  1. Member has improvement in pain associated with endometriosis; and
  2. Treatment duration has not exceeded a total of 24 months

 
Reauthorization duration: 12 months

Coverage duration is limited to 24 months/lifetime


All other treatment durations are considered experimental/investigational.
 


Warning: Thromboembolic disorders and vascular events. Estrogen and progestin combinations, including Oriahnn and Myfembree, increase the risk of thrombotic or thromboembolic disorders, especially in women at increased risk for these events. Oriahnn and Myfembree is contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events, including women over 35 years of age who smoke or women with uncontrolled hypertension. 

De La Cruz MS, Buchanan EM. Uterine Fibroids: Diagnosis and Treatment. Am Fam Physician. 2017 January 15;95(2):100-107. Accessed February 13, 2024

Oriahnn™ (elagolix, estradiol, norethindrone acetate) [package insert]. North Chicago, IL: AbbVie Inc.; May 2020. Available from: https://www.rxabbvie.com/pdf/oriahnn_pi.pdf. Accessed February 13, 2024

Myfembree® (relugolix, estradiol, norethindrone acetate) [package insert]. Bedford Row, UK: Myovant Sciences, Inc.; September 2022. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc3feb73-cc84-43a8-aa32-b262460495e8. Accessed February 13, 2024


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Rx.01.33 Off Label Use
Brand NameGeneric Name
OriahnnElagolix, estradiol, norethindrone acetate
MyfembreeRelugolix, estradiol, norethindrone acetate

Oriahnn®, Myfembree®elagolix, estradiol, and norethindrone acetate, relugolix, estradiol and norethindrone acetate
346
  
4/1/2024Rx.04.7Claim Payment PolicyOyenusi, OluwadamilolaQ4-2023

​Medical necessity is defined in the member's benefits book.  Medications that do not meet the definition of medical necessity are excluded from coverage under the prescription drug benefit. For the medications on this list, there are sufficient amount of formulary alternatives available covered on the formulary. 

Exclusion applies to the medication (chemical entity and formulation) as presented, regardless of brand or generic status available now or in the future. 


The intent of this policy is to communicate medications that are excluded under the member's prescription drug benefit. 

 
Coverage is subject to the terms, conditions, and limitations of the member's contract.

The medications listed below do not meet medical necessity, as defined in the member's benefits book, and will be excluded from coverage (not covered) under the prescription drug benefit.

DrugComponentsRationale
Ibuprofen/famotidine (Duexis®)Ibuprofen 800mg/ famotidine 26.6mg tabletCombination of ibuprofen and famotidine; no advantage over the individual components
Metformin modified, extended release (Glumetza®)Metformin modified, extended release 500mg, 1000mg tabletExtended-release formulation of metformin; other extended release products are available
Naproxen/esomeprazole (Vimovo®)Naproxen 500mg/ esomeprazole 20mg tablet

 
Naproxen 375mg/ esomeprazole 20mg tablet		Combination of naproxen and esomeprazole; no advantage over the individual components; esomeprazole 20mg is available over the counter
Omeprazole/aspirin (Yosprala®)Omeprazole 40mg/ aspirin 81mg tablet

 
Omeprazole 40mg/ aspirin 325mg tablet		Combination of aspirin and omeprazole; no advantage over the individual components
Omeprazole/sodium bicarbonate capsules 40mg/1100mg (Zegerid capsules® 40mg/1100mg)Omeprazole 40mg/ sodium bicarbonate 1100mgCombination of omeprazole and sodium bicarbonate offers no advantage over the individual components, omeprazole alone, or other proton pump inhibitors
Vanos®Fluocinonide 0.1% CreamHigh Potency Alternatives Available: Clobetasol Propionate, Augmented Betamethasone, Halobetasol
 
Prenatal Vitamins, Azesco®, Ziphex®, Pregenna®/PNV® Tab, Zalvit®, DermacinRx Tab Pretrate®Prenatal Vitamins and Minerals With Folic Acid And Iron (Various Dose Combinations)Multiple Generic, Prescription Strength Prenatal Vitamins Are Available
Amlodipine/Celecoxib (Consensi®)Amlodipine 2.5mg/Celecoxib 200mg
Amlodipine 5mg/Celecoxib 200mg
Amlodipine 10mg/Celecoxib 200mg		Combination Of Amlodipine and Celecoxib; No Advantage Over Individual Components
Chlorzoxazone 250 MgChlorzoxazone 250 MgChlorzoxazone 500mg Tablet Is Functionally Scored to Be Broken In Half
Vanadom®Carisoprodol 350 MgAlternatives Available: Carisoprodol 350mg, Tizanidine, Cyclobenzaprine, Baclofen, Methocarbamol, Chlorzoxazone 500mg

Diclofenac potassium (Lofena) 25mg tablet

 

Diclofenac potassium 25mg tabletAlternatives available: diclofenac potassium 50mg, diclofenac sodium delayed release, ibuprofen, naproxen sodium, meloxicam, celecoxib, indomethacin
Methocarbamol 1000mg tabMethocarbamol 1000mg tabMethocarbamol 500mg tablets available. Alternatives available: carisoprodol 350mg, tizanidine, cyclobenzaprine, methocarbamol 500 and 750mg, chlorzoxazone 500mg

 
 


Azesco [prescribing information]. Madisonville, LA: Solubiomix LLC. November 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e2d3e317-4c4a-46ff-a146-90dbc429bed1. Accessed February 13, 2024.

Chlorzoxazone [prescribing information]. Madisonville, LA: Solubiomix LLC. January 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c3d40a90-6df8-4b44-bc61-d7655c52bacb. Accessed February 13, 2024.

Consensi® (amlodipine/celecoxib) [prescribing information]. Tel Aviv, Israel: Kitov Pharma Ltd; June 2018. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210045s000lbl.pdf. Accessed February 13, 2024.

Duexis® (ibuprofen/ famotidine) [package insert]. Deerfield, IL. Horizon Pharma USA Inc. June 2017. Available from: http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=558b9f26-37b2-423b-932d-25a37afe57ec&type=display. Accessed February 13, 2024. 

GlumetzaXR® (metformin extended release) [package insert]. Bridgewater, NJ. Salix Pharmaceuticals. November 2018. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=fb832474-88d9-4e29-95cd-fbc446944cc4&type=display. Accessed February 13, 2024.

Karali TT, Sedo K, Bossart J. Fixed-dose combinations- fixed dose combination products- a review (Part 1- introduction). Drug Development & Delivery. March 2014. Available from: http://drug-dev.com/fixed-dose-combinations-fixed-dose-combination-products-a-review-part-1-introduction.

Lofena® [prescribing information]. Carwi Pharmaceutical Associates, LLC. July 2021. Available at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=49bd64cc-5edb-44f2-8e24-1249f6a76663. Accessed February 13, 2024.

Methocarbamol. In: In Depth Answers [database on the Internet]. Greenwood Village (CO): IBM Corporation; April 2023. Available from: www.micromedexsolutions.com. Accessed February 13, 2024.

Pregenna [prescribing information]. Birmingham, AL: Redmont Pharmaceuticals, LLC. September 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=247c23b1-737e-4599-b9b3-5f4457accf9c. Accessed February 13, 2024.

Vanadom [prescribing information]. Sallus Laboratories, LLC. March 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=3c809da4-4309-4c96-bfa7-f32cdda4be5d. Accessed February 13, 2024.

Vanos® (fluocinonide 0.1% cream) [package insert]. Bridgewater, NJ. Valeant Pharmaceuticals, Inc. May 2017. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=95cb19a0-4b71-4c66-92bd-901cfd223301&type=display. Accessed. February 13, 2024.

Vimovo® (naproxen/ esomeprazole) [package insert]. Deerfield, IL. Horizon Pharma USA Inc. June 2018. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=baa47781-7151-4c75-a9a2-d2eac0a7d55e&type=display. Accessed  February 13, 2024.

Yosprala® (aspirin/ omeprazole) [package insert]. Princeton, NJ. Aralez US Pharmaceuticals Inc. June 2018. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=73f74f6d-e624-4551-8924-1c747ffb2140&type=display#section-1. Accessed February 13, 2024. 

Zalvit [prescribing information]. Branchburg, NJ: National Bio Green Sciences Limited Liability Company. September 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=45668615-30ba-4d21-8ea7-07816369da11. Accessed  February 13, 2024.

Zegerid® (omerprazole/ sodium bicarbonate) [package insert]. Bridgewater, NJ. Salix Pharmaceuticals. June 2018. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=cd6868b9-5824-442b-8d65-4db29ecb70a4&type=display. Accessed February 13, 2024.

Ziphex® [prescribing information]. Fairhope, AL: Ayurax, LLC. March 2022. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4d01ab4f-8e6f-48c9-b793-bda5076fa363. Accessed February 13, 2024.

DermacinRx Pretrate [prescribing information]. PureTek Corporation. February 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ba4a1424-0782-77c0-e053-2a95a9a6e44. Accessed February 13, 2024.


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Rx.04.2 ​Non-FDA approved Products 
medications that are excludedmedications that are excluded
347
  
4/1/2024Rx.01.212CommercialOyenusi, OluwadamilolaQ4-2023

​Fabry Disease is a rare, inherited metabolic disorder characterized by enzyme deficiencies and the resultant accumulation of toxic materials within the lysosomes of cells. It is caused by a mutation in the alpha-Gal A gene located on the X-chromosome. The deficiency of the lysosomal alpha-galactosidse A (alpha-Gal A), which catalyzes the breakdown of globotriaosylceramide (Gb3), leads to accumulation of Gb3 and glycosphingolipids globotriaosylceramide (GL-3) in cells. Certain GLA variants (mutations) causing Fabry Disease result in the production of abnormally folded and less table forms of the alpha-Gal A protein which, however, retain enzymatic activity. Those variants are referred to as amendable variants.  Clinical manifestation of Fabry Disease may include may include severe neuropathic or limb pain; telangiectasias and angiokeratomas; gastrointestinal (GI) symptoms; ocular manifestations; renal manifestations including proteinuria and renal insufficiency; and heat, cold, and exercise intolerance. Eventual progression of microvascular disease of the kidneys, heart, and brain contribute to increased mortality.

Migalastat (Galafold™) is an alpha-galactosidase A (alpha-Gal A) pharmacological chaperone that reversibly binds to the active site of the alpha-galactosidase A (alpha-Gal A) protein (encoded by the galactosidase alpha gene, GLA), which is deficient in Fabryl Disease. This binding stabilizes alpha-Gal A allowing its trafficking from the endoplasmic reticulum into the lysosome where it exerts its action. In the lysosome, at a lower pH and at a higher concentration of relevant substrates, migalastat dissociates from alpha-Gal A allowing it to break down the glycosphingolipids globotriaosylceramide (GL-3) and globotriaosylspingosine (lyso-Gb3).

Migalastat (Galafold™) is indicated for the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene (GLA) variant based on in vitro assay data.


​The intent of this policy is to communicate the medical necessity criteria for migalastat (Galafold) as provided under the member’s prescription drug benefit.

INITIAL CRITERIA: Galafold™ (migalastat) is approved when all of the following are met:

  1. Diagnosis of Fabry disease; and
  2. Member is 16 years of age or older; and
  3. Member has an amenable galactosidase alpha gene (GLA) variant (per FDA labeling information) based on in vitro assay data; and
  4. Galafold will not be used in combination with other drug(s) indicated for the treatment of Fabry disease (e.g., Fabrazyme)

Initial Authorization duration: 6 months 

REAUTHORIZATION CRITERIA: Galafold™ (migalastat) is re-approved when both of the following are met:

  1. Documentation of positive clinical response to therapy, and
  2. Galafold will not be used in combination with other drug(s) indicated for the treatment of Fabry disease (e.g., Fabrazyme)

 

Reauthorization duration: 2 years


None

Galafold™ (migalastat) [prescribing information]. Cranbury, NJ. Amicus Therapeutics U.S., Inc. December 2022. Available at: https://www.amicusrx.com/pi/galafold.pdf. Accessed February 13, 2024

Mauer M, Kopp JB. Fabry disease: treatment and prognosis. UpToDate Web site. Updated December 2022. www.uptodate.com. Accessed February 13, 2024


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Rx.01.33 ​Off-Label Use 
Galafoldmigalastat
348
  
4/1/2024Rx.04.10Claim Payment PolicyOyenusi, OluwadamilolaQ4-2023

Drugs or biologics are approved based on safety and efficacy data from the clinical trials, some of which can take years to complete, especially in the setting where the disease course is long, and an extended period of time would be required to measure the intended clinical benefit. The U.S. Food and Drug Administration (FDA) has an accelerated approval process by which a surrogate or an intermediate clinical endpoint is used as a marker of clinical benefit. This is generally reserved for medications that will treat serious conditions that fill an unmet therapeutic need. A surrogate endpoint used for accelerated approval is a marker; it can be a laboratory measurement, radiographic image, physical sign, or other measure that is thought to predict clinical benefit but is not itself a measure of clinical benefit. Likewise, an intermediate clinical endpoint is a measure of a therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on irreversible morbidity and mortality (IMM). The FDA bases its decision on whether to accept the proposed surrogate or intermediate clinical endpoint on scientific support for that endpoint. Studies that demonstrate a drug's effect on a surrogate or intermediate clinical endpoint must be “adequate and well controlled" as required by the Food, Drug, and Cosmetic (FD&C) Act.

Approval of a drug or a biologic may be withdrawn, or the labeled indication of the drug or biologic may be changed if the confirmatory trial fails to verify clinical benefit or does not demonstrate sufficient clinical benefit to justify the risks associated with the drug or biologic. Hence all drugs or biologics approved via the accelerated approval process have the following statement in the drug label:

“This indication is approved under accelerated approval based on [surrogate marker used in the clinical trial(s)]. Continued approval for this indication may be contingent upon verification of clinical benefit in the confirmatory trial(s)."

Blue Cross and Blue Shield Association (BCBSA) developed a process known as Technology Evaluation Center (TEC) Criteria to evaluate prescription drugs, biologics, devices, or any other product or procedure to determine if they are experimental/investigational despite FDA approval. The review process includes the following five criteria:

  1. The technology must have final approval from the appropriate governmental regulatory bodies.
    • This criterion applies to drugs, biological products, devices and any other product or procedure that must have final approval to market from the FDA or any other federal governmental body with authority to regulate the technology.
    • Any approval that is granted as an interim step in the FDA's or any other federal governmental body's regulatory process is not sufficient.
    • The indications for which the technology is approved need not be the same as those which Blue Cross and Blue Shield Association's Technology Evaluation Center is evaluating.
  2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes.
    • The evidence should consist of well-designed and well-conducted investigations published in peer-reviewed journals. The quality of the body of studies and the consistency of the results are considered in evaluating the evidence.
    • The evidence should demonstrate that the technology can measure or alter the physiological changes related to a disease, injury, illness, or condition. In addition, there should be evidence, or a convincing argument based on established medical facts that such measurement or alteration affects health outcomes.
    • Opinions and evaluations by national medical associations, consensus panels, or other technology evaluation bodies are evaluated according to the scientific quality of the supporting evidence and rationale.
  3. The technology must improve the net health outcome.
    • The technology's beneficial effects on health outcomes should outweigh any harmful effects on health outcomes.
  4. The technology must be as beneficial as any established alternatives.
    • The technology should improve the net health outcome as much as, or more than, established alternatives.
  5. The improvement must be attainable outside the investigational settings.
    • When used under the usual conditions of medical practice, the technology should be reasonably expected to satisfy TEC criteria in numbers 3 and 4 above.

The criteria outlined above are adopted by the Company as a standard process for reviewing new prescription drugs or biologics* for coverage on the pharmacy benefit. 

*Oncology agents are exempt from the review because they are subjected to medical necessity review per criteria established for oncology agents. Line extensions of existing medications using the same brand name and has the same indication are exempt from the review.


​The intent of this policy is to communicate the prescription drug benefit coverage based on medical necessity of prescription drugs or biologics that are approved by the Food and Drug Administration (FDA) despite questionable efficacy.

Coverage is subject to the terms, conditions, and limitations of the member's contract.

Prescription drugs or biologics* that are approved by the FDA under the accelerated approval process are subjected to review to determine if the surrogate or intermediate clinical endpoint used in the trial is an acceptable measure of the drug or biologic's efficacy in the condition for which it is approved, and thus medically necessary. If an FDA approved drug or biologic does not demonstrate efficacy for the disease it is approved to treat, then the drug or biologic is determined to be experimental/investigational, despite FDA approval and is therefore not a covered benefit. Medical necessity is defined in the member's benefits book. Medications that do not meet the definition of medical necessity are excluded from coverage under the prescription drug benefit.

A prescription drug or biologic* is considered medically necessary when the following are met:

  1. The prescription drug or biologic* must have final approval from the FDA with the following statement in the label This indication is approved under accelerated approval based on [surrogate marker used in the clinical trial(s)]. Continued approval for this indication may be contingent upon verification of clinical benefit in the confirmatory trial(s).; and
  2. The scientific evidence must permit conclusions concerning the effect of the prescription drug or biologic on health outcomes; and
  3. The prescription drug or biologic must improve the net health outcome; and
  4. The prescription drug or biologic must be as beneficial as any established alternatives; and
  5. The improvement must be attainable outside the investigational settings.

 

The medications listed below do not meet medical necessity, as defined in the member's benefits book, and will be excluded from coverage (not covered) under the prescription drug benefit. Brand NameGeneric Name
  

*Oncology agents are exempt from the review because they are subjected to medical necessity review per criteria established for oncology agents. Line extensions of existing medications using the same brand name and has the same indication are exempt from the review.
 


Blue Cross and Blue Shield Association. Technology Evaluation and Coverage (TEC) Program. Available at: https://www.ncbi.nlm.nih.gov/books/NBK218445/. Accessed February 13, 2024.

US Food and Drug Administration. Accelerated Approval. Available from: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/accelerated-approval. Accessed February 13, 2024

U.S. Food and Drug Administration. Expediated Programs for Regenerative Medicine Therapies for Serious Conditions – Guidance for Industry. Available from: https://www.fda.gov/media/120267/download. Accessed February 13, 2024

US Food and Drug Administration. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Available from: http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm. Accessed February 13, 2024


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Rx.04.2 Non-FDA Approved Products 

Rx.01.33 Off-Label Use  

Rx.01.67 Oncology Agents 


NANA
349
  
4/1/2024Rx.01.264CommercialOyenusi, OluwadamilolaQ4-2023
Peptic ulcer disease (PUD) involves the development of mucosal defect(s) in the gastric or duodenal wall that typically extend through the muscularis mucosa (innermost layer of mucosa) into deeper layers of the wall (submucosa or muscularis propria). Most peptic ulcers are caused by Helicobacter pylori infection or nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin.

Many patients with PUD remain asymptomatic but may present with nonspecific intermittent symptoms of epigastric pain, early satiety, and/or bloating. Bleeding is the most frequent and severe complication of PUD. Other complications include perforation, penetration, and development of scarring with gastric outlet obstruction. For patients on chronic NSAIDs, consider primary ulcer prophylaxis with proton pump inhibitor (PPI) if there are risk factors for peptic ulcer disease, such as age > 50 years and concomitant use of aspirin, anticoagulants, or corticosteroids.

Glycopyrrolate, an anticholinergic (antimuscarinic) agent, inhibits the action of acetylcholine on parietal cells in the stomach and decreases the volume and acidity of gastric secretions.

Dartisla ODT is indicated in adults to reduce symptoms of a peptic ulcer as an adjunct to treatment of peptic ulcer.
Limitations of Use: Dartisla ODT is not indicated as monotherapy for treatment of peptic ulcer because effectiveness in peptic ulcer healing has not been established.

The intent of this policy is to communicate the medicalnecessity criteria for Glycopyrrolate (Dartisla ODT™) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA Glycopyrrolate (Dartisla ODT™) is approved when ALL of the following are met: 

  1. Diagnosis of peptic ulcer as confirmed by endoscopy; and
  2. One of the following:
    1. Member is on concomitant therapy with a proton-pump inhibitor (PPI) (e.g., lansoprazole, omeprazole); or
    2. Member has inadequate response or inability to tolerate PPI and is receiving concomitant treatment with an H2-receptor antagonist (e.g., famotidine, nizatidine); and
  3. One of the following:
    1. Inadequate response or inability to tolerate generic glycopyrrolate tablets; or 
    2. Member is unable to swallow tablets; and
  4. Prescribed by or in consultation with a gastroenterologist; and
  5. Member is 18 years of age or older  

 
Initial authorization duration: 3 months

 
REAUTHORIZATION CRITERIA Glycopyrrolate (Dartisla ODT™) is reapproved when ALL of the following are met:

  1. One of the following:
    1. Member's peptic ulcer has not healed as confirmed by endoscopy; or
    2. Member has a new peptic ulcer as confirmed by endoscopy; and 
  2. One of the following:
    1. Member is on concomitant therapy with a proton-pump inhibitor (PPI) (e.g., lansoprazole, omeprazole); or
    2. Member has inadequate response or inability to tolerate PPI and is receiving concomitant treatment with an H2-receptor antagonist (e.g., famotidine, nizatidine); and
  3. Member experienced a reduction in peptic ulcer symptoms while on Dartisla ODT™ therapy; and
  4. Prescribed by or in consultation with a gastroenterologist; and
  5. Other correctable factors (e.g., medication noncompliance, NSAID use, H. pylori infection, etc.) have been addressed

 
Reauthorization duration: 3 months


N/A
DynaMed. Peptic Ulcer Disease. EBSCO Information Services. Accessed January 04, 2023. https://www.dynamed.com/condition/peptic-ulcer-disease

Dartisla ODT (glycopyrrolate) [prescribing information]. Parsippany, NJ: Edenbridge Pharmaceuticals, LLC; December 2021. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215019s000lbl.pdf. Accessed February 14, 2024.

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​Rx.01.33 Off Label Use
Dartisla ODT™glycopyrrolate
350
  
4/1/2024Rx.01.177CommercialOyenusi, OluwadamilolaQ4-2023

Flibanserin is a serotonin 5-HT1A agonist and 5-HT2A antagonist. Flibanserin also has moderate antagonist activities at the 5-HT2B, 5-HT2C, and dopamine D4 receptors.  The exact mechanism of flibanserin in the treatment of premenopausal women with hypoactive sexual desire disorder (HSDD) is unknown. Flibanserin was originally studied for depression, but failed to demonstrate efficacy in that area. It was during these clinical trials that researchers recognized the potential benefit of flibanserin for generalized HSDD and continued clinical development in that direction. Although flibanserin has demonstrated improvement in treating HSDD, the overall results of the clinical trials were numerically small, and continued assessment of long-term benefits and risks associated with flibanserin is still warranted.

Bremelanotide is a melanocortin receptor (MCR) agonist that non-selectively activates several receptor subtypes with the following order of potency: MC1R, MC4R, MC3R, MC5R, MC2R. At therapeutic dose levels, binding to MC1R and MC4R is most relevant. Neurons expressing MC4R are present in many areas of the central nervous system (CNS). The mechanism by which VYLEESI improves HSDD in women is unknown. The MC1R is expressed on melanocytes; binding at this receptor leads to melanin expression and increased pigmentation.

HSDD is a disease that represents a subset of symptoms associated with “desire" within the overarching diagnosis of sexual dysfunction. HSDD was a stand-alone diagnosis Diagnostic and Statistical Manual of Mental Disorders (DSM) IV. In DSM V, HSDD is now incorporated into female sexual interest/ arousal disorder (FSIAD).  FSIAD is defined as a lack of, or significantly reduced, sexual interest or arousal for 6 months or greater when a patient meets 3 of the 6 diagnostic criteria.

 

Flibanserin and bremelanotide are indicated for the treatment of premenopausal women with acquired, generalized HSDD, as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to:

·         A co-existing medical or psychiatric condition,

·         Problems within the relationship, or

·         The effects of a medication or other drug substance.

Limitations of Use

·      Flibanserin and bremelanotide are not indicated for the treatment of HSDD in postmenopausal women or in men

·      Flibanserin and bremelanotide are not indicated to enhance sexual performance


The intent of this policy is to communicate the medicalnecessity criteria for flibanserin (Addyi®) and bremelanotide (Vyleesi™) as provided under the member's prescription drug benefit.

INITIAL CRITERIA Flibanserin (Addyi®) is approved when ALL of the following are met:

  1. Diagnosis of one of the following:
    1. Acquired, generalized hypoactive sexual desire disorder (HSDD); or
    2. Female sexual interest/arousal disorder; and
  2. Member is premenopausal; and
  3. Symptoms of HSDD have persisted for at least 6 months; and
  4. Member is 18 years of age or older

 

Initial authorization duration: 3 months

RE-AUTHORIZATION CRITERIA Flibanserin (Addyi®) is re-approved when ALL of the following are met:

  1. Positive clinical response to flibanserin (Addyi®) therapy; and 
  2. Member continues to be premenopausal


Reauthorization duration: 12 months

INITIAL CRITERIA Bremelanotide (Vyleesi™) is approved when ALL of the following are met:

  1. Diagnosis of one of the following:
    1. Acquired, generalized hypoactive sexual desire disorder (HSDD); or
    2. Female sexual interest/arousal disorder; and
  2. Symptoms of HSDD or female sexual interest/arousal disorder have persisted for at least 6 months; and
  3. Member is premenopausal; and
  4. Member does not have either of the following:
    1. Uncontrolled hypertension; or
    2. Known cardiovascular disease; and
  5. Member is 18 years of age or older

 
Initial authorization duration: 3 months

REAUTHORIZATION CRITERIA Bremelanotide (Vyleesi™) is re-approved when ALL of the following are met:

  1. Documentation of positive clinical response to Vyleesi™ therapy; and
  2. Member continues to be premenopausal; and
  3. Member does not have either of the following:
    1. Uncontrolled hypertension; or
    2. Known cardiovascular disease


Reauthorization duration: 12 months


Addyi®:

WARNING: HYPOTENSION AND SYNCOPE IN CERTAIN SETTINGS

Interaction with Alcohol

The use of ADDYI and alcohol together close in time increases the risk of severe hypotension and syncope. Counsel patients to wait at least two hours after consuming one or two standard alcoholic drinks before taking ADDYI at bedtime or to skip their ADDYI dose if they have consumed three or more standard alcoholic drinks that evening.

Contraindicated with Strong or Moderate CYP3A4 Inhibitors

The concomitant use of ADDYI and moderate or strong CYP3A4 inhibitors increases flibanserin concentrations, which can cause severe hypotension and syncope. Therefore, the use of moderate or strong CYP3A4 inhibitors is contraindicated in patients taking ADDYI. 

Contraindicated in Patients with Hepatic Impairment

The use of ADDYI in patients with hepatic impairment increases flibanserin concentrations, which can cause severe hypotension and syncope.  Therefore, ADDYI is contraindicated in patients with hepatic impairment


Addyi® (flibanserin) [package insert]. Raleigh, NC. Sprout Pharmaceuticals. September 2021. Available at: mk0speedyaddyip6a9xx.kinstacdn.com/wp-content/uploads/2021/03/Full-Prescribing-Information.pdf. Accessed February 14, 2024.

Vyleesi™ (bremelanotide) [package insert]. Waltham, MA. AMAG Pharmaceuticals, Inc. February 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf. Accessed February 14, 2024.

American Psychiatric Association. Diagnostic and Statistical manual of Mental Disorders, 5th edition (DSM V). Washington, DC: In Section II, Sexual Dysfunctions, Female Sexual Interest/Arousal Disorder. Accessed February 14, 2024.

Flibanserin. Micromedex. Available at: http://www.micromedexsolutions.com/. Accessed February 14, 2024.

1112/18/202312/18/20244/1/2024 1:25 AMNo presence informationsrv_ppsgw_P
Off Label Use Rx.01.33

Quantity Level Limits for Pharmaceuticals Covered Under the Pharmacy Benefit Rx.01.76

​Brand name​Generic name
​Addyi® ​flibanserin
​Vyleesi™ ​bremelanotide

Addyi®, Vyleesi™flibanserin, bremelanotide
352
  
4/1/2024Rx.01.179CommercialOyenusi, OluwadamilolaQ4-2023
Hypophosphatasia (HPP) is a rare, genetic disease resulting from loss of function mutations in the ALPL gene encoding tissue nonspecific alkaline phosphatase (TNSALP). The deficiency in TNSALP enzyme activity leads to elevated TNSALP substrates, including inorganic pyrophosphate (PPi). Elevated PPi blocks hydroxyapatite crystal growth, which inhibits bone mineralization. The disease is characterized by defective mineralization of teeth and bones, leading to bone fractures, deformities, and tooth loss.  HPP is a highly variable disease and severity correlates to the residual TNSALP activity.  The overall incidence and prevalence of HPP in the general population is unknown.  HPP is estimated to affect 1 in every 100,000 live births.  Milder cases of the disease may be undiagnosed or misdiagnosed, impacting the ability to determine frequency in the general population. 

Asfotase alfa (Strensiq®), a recombinant TNSALP enzyme replacement therapy, is indicated for the treatment of patients with perinatal/ infantile- and juvenile-onset HPP. Asfotase alfa represents the first approved therapy for HPP.  Prior to approval of asfotase alfa, HPP patients were managed with symptomatic treatments.

Hereditary orotic aciduria (HOA) is a rare metabolic disease that results from the disorder of enzyme uridine-5-monophosphate (UMP) synthase. This enzyme is responsible for converting orotic acid to UMP in pyrimidine synthesis. Without this step, orotic acid level in urine will elevate and no UMP production. HOA is characterized by meganoblastic anemia, crystalluria, as well as retarded growth and development. There are less than 20 HOA cases in the world.

Uridine triacetate (Xuriden®), is a pyrimidine analog indicated in adult and pediatric patients for the treatment of hereditary orotic aciduria. It acts as a source of uridine, compensating for the deficiency of UMP in pyrimidine synthesis. 

The intent of this policy is to communicate the medical necessity criteria for asfotase alfa (Strensiq®) and uridine triacetate (Xuriden®) as provided under the member's prescription drug benefit.

Perinatal/infantile or juvenile-onset hypophosphatasia

INITIAL CRITERIA: Asfotase alfa (Strensiq®) is approved when ALL of the following are met:

  1. Submission of documentation (e.g., chart note) confirming diagnosis of perinatal/infantile or juvenile-onset hypophosphatasia (HPP); and
  2. Prescribed by or in consultation with a medical geneticist or other specialist that treats inborn errors of metabolism; and
  3. For member requesting the 80mg/0.8ml vial: member's weight is greater than or equal to 40kg

 

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: Asfotase alfa (Strensiq®) is re-approved when there is positive clinical response to therapy
 

Reauthorization duration: 2 years

_________________________________________________________________________________________

Hereditary orotic aciduria
 

INITIAL CRITERIA: Uridine triacetate (Xuriden®) is approved when ALL of the following are met:

  1. Submission of documentation (e.g., chart note) confirming diagnosis of hereditary orotic aciduria; and
  2. Prescribed by or in consultation with a medical geneticist or other specialist that treats inborn errors of metabolism

 

Initial authorization duration: 2 years

 
REAUTHORIZATION CRITERIA: Uridine triacetate (Xuriden®) is re-approved when there is positive clinical response to therapy

Reauthorization duration: 2 years



N/A
Scott LJ. Asfotase alfa: a review in paediatric-onset hypophosphatasia. Drugs. 2016;76:255-62.

Strensiq® (asfotase alfa) [prescribing information]. New Haven, CT. Alexion Pharmaceuticals, Inc. June 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=3387574f-5eaa-4501-a71d-4cbfbd563031&type=display.  Accessed February 15, 2024.

Nyhan WL. Disorder of purine and pyrimidine metabolism. Molecular Genetics and Metabolism, Volume 86, Issues 1–2, September–October 2005. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16176880. Accessed February 15, 2024.

Xuriden® (uridine triacetate) [prescribing information]. Gaithersburg, MD. Wellstat Therapeutics Corporation. August 2023. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=40606ca9-4f14-45b7-8632-fc2d17d11a2e&type=display. Accessed February 15, 2024.

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Off-Label Use Rx.01.33
Strensiq®, Xuriden®asfotase alfa, uridine triacetate
353
  
4/1/2024Rx.01.60CommercialOyenusi, OluwadamilolaQ4-2023
Consideration for non-standard formula coverage is available only to infants enrolled in an AmeriHealth New Jersey plan that includes coverage for prescription drugs. In accordance with New Jersey Senate Bill 1839, specialized non-standard infant formula is covered when an infant is diagnosed as having multiple food protein intolerance that has not been responsive to trials of standard non-cow milk based formulas. Standard formulas include milk-based, soy-based, and milk-based lactose free products.
 
Specialized formulas for infants with metabolic disorders are not covered through the prescription drug benefit. Metabolic formulas are covered through the medical benefit.

Coverage for non-standard formulas is subject to utilization review, including periodic review, of the continued medical necessity of the specialized infant formula. Under Senate Bill 1839, “infant" is defined as birth through age 12 months.

The intent of this policy is to communicate the medicalnecessity criteria for infant formulas as provided under the member's prescription drug benefit.

Non-standard formulas, including, but not limited to, Enfamil®, Pregestimil®, Neocate®, EleCare ®, Alimentum®, Similac Expert Care Alimentum®, Nutramigen®, PurAmino®, Gerber Extensive HA® are approved when all of the following are met:

  1. Documentation that the infant is 12 months old or younger; and
  2. Documentation of a diagnosis of multiple food protein intolerance; and
  3. Documentation infant has not been responsive to at least one trial of a standard non-cow milk-based formula, including soybean or goat milk

 

Authorization duration: Through member's age of 12 months

QUANTITY LIMIT = four cases for a 30-day supply per copay or co-insurance


N/A
New Jersey Senate Bill 1839, dated January 22, 2001. Available at: https://pub.njleg.state.nj.us/Bills/2000/S2000/1839_I1.PDF. Accessed February 14, 2024.
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Off-Label Use policy Rx.01.33
N/A
infant formulasinfant formulas
354
  
4/1/2024Rx.01.199CommercialOyenusi, OluwadamilolaQ4-2023
Ibuprofen/ famotidine (Duexis®), naproxen/ esomeprazole (Vimovo®), and aspirin/ omeprazole (Yosprala®)

Fixed dose combinations (FDC) contain two or more active ingredients incorporated into a single dosage presentation (eg, tablet, capsule, patch).  The value of FDCs depends upon the product, the condition being treated, and the target population for the product.

Ibuprofen/ famotidine (Duexis®) is an FDC containing 800mg of ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), and 26.6 mg of famotidine, a histamine H2-receptor antagonist (H2RA).  It is indicated for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal ulcers, which in the clinical trials was defined as a gastric and/or duodenal ulcer, in patients who are taking ibuprofen for those indications. The clinical trials primarily enrolled patients less than 65 years of age without a prior history of gastrointestinal ulcer. Controlled trials do not extend beyond 6 months. 

Naproxen/ esomeprazole (Vimovo®) is an FDC containing 375mg or 500mg of naproxen, an NSAID, and 20mg of esomerpazole, a proton pump inhibitor (PPI). It is indicated for the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis and to decrease the risk of developing gastric ulcers in patients at risk of developing NSAID-associated gastric ulcers. Naproxen/ esomeprazole (Vimovo®) is not recommended for initial treatment of acute pain because the absorption of naproxen is delayed compared to absorption from other naproxen-containing products. Controlled studies do not extend beyond 6 months.

Aspirin/ omeprazole (Yosprala®) is an FDC containing 81mg or 325mg of aspirin, an antiplatelet and 40mg of omeprazole, a PPI. It is indicated for patients who require aspirin for secondary prevention of cardiovascular and cerebrovascular events and who are at risk of developing aspirin associated gastric ulcers.  Controlled studies do not extend beyond 6 months.

These FDCs offer no clinical advantage over the individual components.  There are several formulary alternatives available.

Metformin modified extended release (Glumetza®)

Metformin is a biguanide that improves glucose tolerance in patients with type 2 diabetes mellitus (T2DM), lowering basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Metformin does not produce hypoglycemia in patients with T2DM or in healthy subjects except in special circumstances and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged, while fasting insulin levels and day-long plasma insulin response may actually decrease.

Omeprazole/ sodium bicarbonate (Zegerid®)

Proton Pump Inhibitors (PPIs) suppress gastric acid secretion by inhibiting hydrogen-potassium adenosinetriphosphatase (H+/K+ ATPase) on the surface of parietal cells, the final step in acid secretion. PPIs are the most potent gastric acid suppression agents and are most effective when the parietal cells are stimulated to produce acid post-prandially.

PPIs are useful in treating peptic ulcer disease (including prevention and treatment of NSAID induced gastric ulcers), gastroesophageal reflux disease (GERD) with and without esophageal erosions, hypersecretory diseases, and helicobacter pylori infections (as part of an antibiotic containing regimen).


Fluocinonide 0.1% cream (Vanos®) is a super high potency topical corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid responsive dermatoses in patients 12 years of age or older.

Amlodipine/celecoxib (Consensi®) is a combination of amlodipine besylate, a calcium channel blocker, and celecoxib, a nonsteroidal anti-inflammatory (NSAID), indicated for patients for whom treatment with amlodipine for hypertension and celecoxib for osteoarthritis are appropriate. Lowering blood pressure reduces the risk of fatal and nonfatal CV events, primarily strokes and infarctions. Consensi® is available in three fixed-dose combinations (FDC) where celecoxib dose is constant: 2.5 mg/200 mg, 5 mg/200 mg, and 10 mg/ 200 mg.

Chlorzoxazone 250mg is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions. The mechanism of action has not been clearly identified but may be related to its sedative properties. The drug is available in 250mg, 375mg, 500mg, and 750mg. Standard dose for the treatment of acute musculoskeletal pain is 500mg to 750mg orally three to four times daily. If 250mg per dose is required, the 500mg tablet is functionally scored that can easily be broken in half.  

Vanadom® is indicated for the relief of discomfort associated with acute, painful musculoskeletal conditions in adults. The mechanism of action has not been clearly identified. In animal studies, muscle relaxation induced by carisoprodol is associated with altered interneuronal activity in the spinal cord and in the descending reticular formation of the brain.

DermacinRx tab Pretrate® contains vitamin A, vitamin C, vitamin D3, vitamin E, thiamin, riboflavin, niacin, vitamin B6, folate, vitamin b12, choline, calcium, iron, iodine, magnesium, zinc, selenium, manganese, chromium, and molybdenum. DermacinRx tab Pretrate® indicated to provide vitamins and minerals to women throughout pregnancy and during the postnatal period for both lactating and non-lactating mothers, and throughout the childbearing years.

Diclofenac potassium (Lofena®) is a potent inhibitor of prostaglandin synthesis in vitro. It is indicated for treatment of primary dysmenorrhea, relief of mild to moderate pain, relief of the signs and symptoms of osteoarthritis, and relief of the signs and symptoms of rheumatoid arthritis.

Methocarbamol is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions. The mode of action of methocarbamol has not been clearly identified but may be related to its sedative properties.



The intent of this policy is to communicate the medicalnecessity criteria for ibuprofen/ famotidine (Duexis®), naproxen/ esomeprazole (Vimovo®), aspirin/ omeprazole (Yosprala®), metformin modified extended release (Glumetza®), fluocinonide 0.1% cream (Vanos®), omeprazole/sodium bicarbonate (Zegerid®) capsules, amlodipine/celecoxib (Consensi®), chlorzoxazone 250mg, Vanadom® 350mg, and prenatal vitamins (Azesco®/Ziphex®, Zalvit®, Pregenna®/PVN® tab, DermacinRx tab Pretrate®), methocarbamol 1000mg tablet, and diclofenac potassium (Lofena) as provided under the member's prescription drug benefit

 
INITIAL CRITERIA: Ibuprofen/ famotidine (Duexis®), naproxen/ esomeprazole (Vimovo®), aspirin/ omeprazole (Yosprala) or amlodipine/celecoxib (Consensi®) is approved when there is an inadequate response or inability to tolerate a TWO-week trial of BOTH of the following:

  1. Concurrent administration of each of the components of the requested product; and
  2. At least FOUR generic alternatives (when available) of each of the individual components of the requested product
DrugComponentsGeneric alternative(s)
Ibuprofen/famotidine (Duexis®)ibuprofenE.g., celecoxib, diclofenac, etodolac, meloxicam, naproxen
​famotidineE.g., Cimetidine, nizatidine
Naproxen/esomeprazole (Vimovo®)naproxenE.g., celecoxib, diclofenac, etodolac, ibuprofen, meloxicam
​esomeprazoleE.g., pantoprazole, omeprazole, rabeprazole
Omeprazole/aspirin (Yosprala®)aspirinNA
​omeprazoleE.g., pantoprazole, rabeprazole, lansoprazole
Amlodipine/celecoxib (Consensi®)amlodipineE.g., diltiazem, felodipine, nifedipine, nisoldipine
​celecoxibE.g., celecoxib, diclofenac, etodolac, ibuprofen, meloxicam

 

Initial authorization duration: 6 months 

REAUTHORIZATION CRITERIA: Ibuprofen/famotidine (Duexis®), naproxen/esomeprazole (Vimovo®), aspirin/omeprazole (Yosprala®), or amlodipine/celecoxib (Consensi®) is re-approved when there is documentation of positive clinical response to therapy.
  
Reauthorization duration: 6 months 
  
INITIAL CRITERIA: Metformin modified extended release (Glumetza®) is approved when there is inadequate response or inability to tolerate BOTH of the following:

  1. Two generic forms of extended-release metformin; and
  2. Glucophage XR

 

Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Metformin modified extended release (Glumetza®) is re-approved when there is documentation of positive clinical response to therapy such as reduction in A1c.

Reauthorization duration: 6 months

INITIAL CRITERIA: Omeprazole/sodium bicarbonate 40mg-1.1g (Zegerid®) capsules is approved when there is documentation of BOTH of the following:

  1. An FDA or compendia approved indication; and
  2. Inadequate response to a two-week trial or inability to tolerate THREE of the following generic proton pump inhibitors administered concurrently with sodium bicarbonate oral tablet:
    1. omeprazole 
    2. lansoprazole
    3. pantoprazole
    4. rabeprazole


Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Omeprazole/sodium bicarbonate 40mg-1.1g (Zegerid®) capsules is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 6 months

Quantity limit: 2 capsules per day; 60 capsules per 30 days
Omeprazole/sodium bicarbonate 40mg-1.1g (Zegerid®) increased quantity limits is approved when ONE of the following is met:

  1. Pathological hypersecretory condition including Zollinger-Ellison syndrome; or
  2. Barrett's esophagus; or
  3. Upper gastrointestinal bleed (gastric or duodenal); or
  4. Inadequate response to once daily proton pump inhibitor therapy with ONE of the following:
    1. Gastroesophageal reflux disease (GERD) with nocturnal symptoms
    2. GERD or erosive esophagitis for member less than 11 years old
    3. Laryngopharyngeal reflux
    4. Treatment for the eradication of H pylori with triple therapy (duration of therapy will be limited to 14 days)

 

Approval duration: 6 months

INITIAL CRITERIA: Vanos® is approved when ALL of the following are met:

  1. Diagnosis of the relief of inflammatory and pruritic manifestations of corticosteroid response dermatoses; and
  2. Member is 12 years or older; and
  3. Documentation of an inadequate response or inability to tolerate THREE class-1 superpotent topical steroids (e.g., clobetasol propionate, augmented betamethasone, halobetasol)

 

Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Vanos® is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 6 months

INITIAL CRITERIA: Azesco®, Pregenna®/PNV® tab, Zalvit®, Ziphex®, or DermacinRx tab Pretrate® is approved when there is an inadequate response or inability to tolerate at least three generic, prescription strength prenatal vitamins.

Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Azesco®, Pregenna®/PNV® tab, Zalvit®, Ziphex®, or DermacinRx tab Pretrate® is re-approved when there is documentation of continued need for the prenatal vitamin (i.e., pregnancy, breast feeding).

Reauthorization duration: 6 months

INITIAL CRITERIA: Chlorzoxazone 250mg is approved when there is an inadequate response or inability to tolerate BOTH of the following:

  1. Chlorzoxazone 500mg*; and
  2. At least THREE of the following generics:
    1. Metaxalone; or
    2. Carisoprodol; or
    3. Tizanidine; or
    4. Cyclobenzaprine; or
    5. Baclofen; or
    6. Methocarbamol

*Chlorzoxazone 500 mg is functionally scored to be broken in half.

Initial authorization duration: 3 months

REAUTHORIZATION CRITERIA: Chlorzoxazone 250mg is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 3 months

INITIAL CRITERIA: Vanadom 350mg is approved when there is an inadequate response or inability to tolerate BOTH of the following:

  1. Carisoprodol 350mg; and
  2. At least THREE of the following generics:
    1. Metaxalone; or
    2. Tizanidine; or
    3. Cyclobenzaprine; or
    4. Baclofen; or
    5. Methocarbamol; or
    6. Chlorzoxazone 500mg

 

Initial authorization duration: 1 month

REAUTHORIZATION CRITERIA: Vanadom 350mg is re-approved when there is documentation of positive clinical response to therapy.
 

Reauthorization duration: 1 month

INITIAL CRITERIA Diclofenac potassium (Lofena) 25mg tablet is approved when there is an inadequate response or inability to tolerate at least THREE of the following generics:

  1. Diclofenac potassium 50mg; or
  2. Diclofenac sodium; or
  3. Ibuprofen, or
  4. Naproxen; or
  5. Meloxicam; or
  6. Celecoxib; or
  7. Indomethacin

 
Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA Diclofenac potassium (Lofena) 25mg tablet is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 6 months
 
INITIAL CRITERIA: Methocarbamol 1000mg is approved when there is an inadequate response or inability to tolerate BOTH of the following: 

  1. Methocarbamol 500mg tablets; and 
  2. At least three of the following generics: 
    1. Metaxalone; or 
    2. Tizanidine; or 
    3. Cyclobenzaprine; or 
    4. Chlorzoxazone 500mg; or 
    5. Carisoprodol 350mg

 
Initial authorization duration: 1 month 

REAUTHORIZATION CRITERIA: Methocarbamol 1000mg is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 1 month


NSAIDs (ibuprofen, naproxen, Consensi®, Duexis®,Vimovo®, Lofena®)

Cardiovascular Risk: NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.

NSAIDs are contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.

Gastrointestinal Risk: NSAIDs cause an increased risk of serious gastrointestinal adverse reactions including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These reactions can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events.

Metformin (Glumetza®)

Lactic acidosis is a rare, but serious, complication that can occur because of metformin accumulation. The risk increases with conditions such as renal impairment, sepsis, dehydration, excess alcohol intake, hepatic impairment, and acute congestive heart failure.

The onset is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress.

Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate. If acidosis is suspected, discontinue metformin containing agent and immediately hospitalize the patient.

DermacinRx tab Pretrate®

Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6.

Folic acid in doses above 0.1 mg daily may obscure pernicious anemia, in that hematologic remission can occur while neurological manifestations remain progressive. This may result in severe nervous system damage before the correct diagnosis is made.

This product is contraindicated in patients with known hypersensitivity to any of its ingredients; also, all iron compounds are contraindicated in patients with hemosiderosis, hemochromatosis, or hemolytic anemias. Pernicious anemia is a contraindication, as folic acid may obscure its signs and symptoms.


Azesco [prescribing information]. Madisonville, LA: Solubiomix LLC. November 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e2d3e317-4c4a-46ff-a146-90dbc429bed1. Accessed February 15, 2024.

Chlorzoxazone [prescribing information]. Madisonville, LA: Solubiomix LLC. January 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c3d40a90-6df8-4b44-bc61-d7655c52bacb. Accessed February 15, 2024.

Consensi® (amlodipine/celecoxib) [prescribing information]. Tel Aviv, Israel: Kitov Pharma Ltd; November 2020. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210045s000lbl.pdf. Accessed February 15, 2024

Duexis® (ibuprofen/ famotidine) [package insert]. Deerfield, IL. Horizon Pharma USA Inc. June 2019. Available from: http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=558b9f26-37b2-423b-932d-25a37afe57ec&type=display. Accessed February 15, 2024.

Glumetza® (metformin HCL ER) [package insert]. Bridgewater, NJ. Salix Pharmaceuticals. April 2017. Available from: https://shared.salix.com/shared/pi/glumetza-pi.pdf. Accessed February 15, 2024.

Lofena® [prescribing information]. Carwi Pharmaceutical Associates, LLC. July 2021. Available at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=49bd64cc-5edb-44f2-8e24-1249f6a76663. Accessed February 15, 2024.

Karali TT, Sedo K, Bossart J. Fixed-dose combinations- fixed dose combination products- a review (Part 1- introduction). Drug Development & Delivery. March 2014. Available from: http://www.drug-dev.com/Main/Back-Issues/FIXEDDOSE-COMBINATIONS-FixedDose-Combination-Produ-661.aspx.

Methocarbamol. In: In Depth Answers [database on the Internet]. Greenwood Village (CO): IBM Corporation; April 2023. Available from: www.micromedexsolutions.com. Accessed February 15, 2024.

Pregenna [prescribing information]. Birmingham, AL: Redmont Pharmaceuticals, LLC. September 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=247c23b1-737e-4599-b9b3-5f4457accf9c. Accessed February 15, 2024.
Vanadom (carisoprodol) [prescribing information]. Birmingham, AL: Sallus Laboratories, LLC; March 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3c809da4-4309-4c96-bfa7-f32cdda4be5d. Accessed February 15, 2024.

Vanos® (fluocinonide 0.1% cream) [package insert]. Bridgewater, NJ. Valeant Pharmaceuticals, Inc. May 2017. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=95cb19a0-4b71-4c66-92bd-901cfd223301&type=display. Accessed February 15, 2024.


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 Rx. 01.33 Off-Label Use
Brand NameGeneric Name
Chlorzoxazone 250mgChlorzoxazone 250mg
Consensi®amlodipine/celecoxib
Duexis®Ibuprofen/ famotidine
Vimovo®Naproxen/ esomeprazole
Yosprala®Aspirin/ omeprazole
Glumetza®Metformin, modified extended release
Zegerid® capsOmeprazole/ sodium bicarbonate
Vanos®Fluocinonide cream 0.1%
Azesco®/Ziphex®Prenatal vitamin/ferrous gluconate/folic acid
Zalvit®Prenatal vitamin/ferrous bisglycinate chelate/folic acid
Pregenna®/PNV® tabPrenatal vitamin/ferrous gluconate/folic acid
DermacinRx tab Pretrate®Prenatal vitamin/ferrous fumarate/folic acid tablet
Vanadom® 350mgCarisoprodol  350mg
Lofena®Diclofenac potassium
Methocarbamol 1000mgMethocarbamol 1000mg

Duexis®, Vimovo®, Yosprala®, Glumetza®, Vanos®, Zegerid®, Consensi®, Vanadom® 350mg, Azesco®/Ziphex®, Zalvit®, Pregenna®/PVN® tab, DermacinRx tab Pretrate®ibuprofen/ famotidine, naproxen/ esomeprazole, aspirin/ omeprazole, metformin modified extended release, fluocinonide 0.1% cream, omeprazole/sodium bicarbonate, amlodipine/celecoxib, chlorzoxazone 250mg, prenatal vitamins, methocarbamol 1000mg tablet
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4/1/2024Rx.01.254CommercialOyenusi, OluwadamilolaQ4-2023

Progressive familial intrahepatic cholestasis is a group of rare genetic inherited disorders which are caused by defect in bile secretion and present with intrahepatic cholestasis, usually in infancy and childhood. This disorder causes a progressive liver disease and can lead to cirrhosis and end-stage liver disease. The common symptom in patients with progressive familial intrahepatic cholestasis is severe and debilitating pruritus.

Odevixibat is a reversible inhibitor of the ileal bile acid transporter (IBAT). It decreases the reabsorption of bile acids (primarily the salt forms) from the terminal ileum. Although the complete mechanism by which odevixibat improves pruritus in patients with progressive familial intrahepatic cholestasis.is unknown, it may involve inhibition of the IBAT.

BYLVAY is an ileal bile acid transporter (IBAT) inhibitor indicated for:

Progressive Familial Intrahepatic Cholestasis (PFIC)

  • the treatment of pruritus in patients 3 months of age and older with progressive familial intrahepatic cholestasis (PFIC).
  • Limitation of Use: BYLVAY may not be effective in a subgroup of PFIC type 2 patients with specific ABCB11 variants resulting in non-functional or complete absence of the bile salt export pump protein.

Alagille Syndrome (ALGS)

  • the treatment of cholestatic pruritus in patients 12 months of age and older with Alagille syndrome (ALGS).

The intent of this policy is to communicate the medical necessity criteria for Odevixibat (Bylvay™) as provided under the member's prescription drug benefit.

Progressive Familial Intrahepatic Cholestasis (PFIC)

INITIAL CRITERIA: Odevixibat (Bylvay™) is approved when ALL of the following are met:

  1. Diagnosis of pruritus associated with progressive familial intrahepatic cholestasis (PFIC); and
  2. Confirmed molecular diagnosis of PFIC type 1, 2, or 3; and
  3. Member is 3 months of age or older; and
  4. Prescribed dose is consistent with FDA-approved package labeling and does not exceed a total daily dose of 6mg; and
  5. Prescribed by or in consultation with a hepatologist or gastroenterologist

Initial authorization duration: 6 months


REAUTHORIZATION CRITERIA: Odevixibat (Bylvay™) is re- approved when BOTH of the following are met:

  1. Documentation of positive clinical response to therapy (e.g., improvement in pruritus symptoms); and
  2. Prescribed dose is consistent with FDA-approved package labeling and does not exceed a total daily dose of 6mg

Reauthorization duration: 2 years

___________________________________________________________________________________________

Alagille Syndrome (ALGS)

INITIAL CRITERIA: Odevixibat (Bylvay™) is approved when ALL of the following are met:

  1. Diagnosis of Alagille Syndrome (ALGS); and
  2. Molecular genetic testing confirms mutations in the JAG1 or NOTCH2 gene; and
  3. Member is experiencing both of the following:
    1. Moderate to severe cholestatic pruritus; and
    2. Serum bile acid concentration above the upper limit of the normal reference for the reporting laboratory; and
  4. Inadequate response or inability to tolerate at least TWO of the following treatments used for the relief of pruritus:
    1. Ursodeoxycholic acid (e.g., Ursodiol);
    2. Antihistamines (e.g., diphenhydramine, hydroxyzine);
    3. Rifampin;
    4. Bile acid sequestrants (e.g., cholestyramine, colestipol, colesevelam); and
  5. Member is 12 months of age or older; and
  6. Prescribed by or in consultation with a hepatologist or gastroenterologist

Initial authorization duration: 6 months

 

REAUTHORIZATION CRITERIA: Odevixibat (Bylvay™) is re- approved when the following is met:

  1. Documentation of positive clinical response to therapy (e.g., reduced bile acids, reduced pruritus severity score)

Reauthorization duration: 2 years


N/A
Srivastava A. Progressive familial intrahepatic cholestasis. J Clin Exp Hepatol. 2014;4(1):25-36. doi:10.1016/j.jceh.2013.10.005. Accessed February 14, 2024.

BylvayTM (odevixibat) [package insert]. Boston, MA: Albireo Pharma, Inc.; January 2024. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215498s000lbl.pdf?utm_medium=email&utm_source=govdelivery. Accessed February 14, 2024.

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​Rx.01.33 Off Label Use policy
Bylvay™odevixibat
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4/1/2024Rx.01.168CommercialOyenusi, OluwadamilolaQ4-2023
Efinaconazole (Jublia®) is an azole antifungal that inhibits fungal lanosterol 14α-demethylase involved in the biosynthesis of ergosterol, a constituent of fungal cell membranes.  Efinaconazole (Jublia®) is indicated for the topical treatment of onychomycosis of the toenails due to Trichophyton rubrum and Trichophyton mentagophytes.

Tavaborole (Kerydin®) is an oxaborole antifungal that inhibits fungal protein synthesis through the inhibition of an aminocyl-transfer ribonucleic acid (tRNA) synthetase (AARS).  Tavaborole (Kerydin®) is indicated for the topical treatment of onychomycosis of the toenails due to Trichophyton rubrum and Trichophyton mentagophytes. 

Ciclopirox (Cilodan®) is a hydroxypyridinone antifungal agent that inhibits the growth of pathogenic dermatophytes.  The exact mechanism of action is unknown.  Ciclopirox may inhibit transport of certain essential substrates into fungal cells, interfere with the synthesis of proteins, RNA and DNA, and alter cell permeability, osmotic fragility and endogenous respiration.  Ciclopirox (Ciclodan®) is indicated as a component of a comprehensive management program for topical treatment of immunocompetent patients with mild to moderate onychomycosis of fingernails and toenails, without lunula involvement, due to Trichophyton rubrum.

The intent of this policy is to communicate the medicalnecessity criteria for efinaconazole (Jublia®), tavaborole (Kerydin®), and ciclopirox (Ciclodan®,) 8% topical solution as provided under the member’s prescription drug benefit.

Efinaconazole (Jublia®), tavaborole (Kerydin®), or ciclopirox (Ciclodan®) 8% topical solution is approved when ALL of the following are met:

  1. Diagnosis of onychomycosis confirmed by one of the following:
    1. Positive potassium hydroxide (KOH) preparation; or
    2. Culture; or
    3. Histology and
  2. The member does not have dermatophytomas or lunula (matrix) involvement; and
  3. Inadequate response or inability to tolerate BOTH of the following:
    1. oral generic terbinafine; and
    2. oral generic itraconazole OR topical generic ciclopirox; and
  4. One of the following:
    1. For efinaconazole (Jublia®) and tavaborole (Kerydin®) only, member is 6 years of age or older; or
    2. For ciclopirox (Ciclodan®) 8% topical solution only, member is 12 years of age or older; and
  5. For Brand Kerydin only, inadequate response or inability to tolerate generic tavaborole

Authorization duration: 1 year


N/A
Ciclodan® (ciclopirox) [package insert]. Fairfield, NJ. Medimetriks Pharmaceuticals, Inc. November 2018. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=246676e5-60a0-41dc-b665-30d5e670b426&type=display. Accessed February 14, 2024.

Jublia® (efinaconazole) [package insert]. Bridgewater, NJ. Valeant Pharmaceuticals North America, LLC. March 2022. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=922d4d25-c530-11e1-9b21-0800200c9a66&type=display. Accessed February 14, 2024.

Kerydin® (tavaborole) [package insert]. Palo Alto, CA. Anacor Pharmaceuticals, Inc. August 2018. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1ae61072-bca0-43f0-a741-07bda2d50c87&type=display. Accessed February 14, 2024.



1112/18/202312/18/20244/1/2024 1:26 AMNo presence informationsrv_ppsgw_P
​Off-Label Use policy Rx.01.33


Brand NameGeneric Name
Jublia®Efinaconazole
Kerydin®Tavaborole
Ciclodan®Ciclopirox

Jublia®, Kerydin®, Ciclodan®efinaconazole, tavaborole, ciclopirox 8% topical solution
358
  
4/1/2024Rx.01.224CommercialOyenusi, OluwadamilolaQ4-2023
In the United States, the prevalence rate of peanut allergy is about 1 to 2 percent. Nine major and minor allergenic proteins in peanut, designated Ara h 1 to 9, have been identified that are responsible for IgE-mediated reactions. The risk factors for the development of peanut allergy include a family or personal history of atopic disease, severe atopic dermatitis and/or egg allergy in young infants, and a family history of peanut allergy. The majority of allergic reactions to peanut are systemic. Symptoms can be isolated to a single organ system, most commonly the skin (e.g. urticaria, angioedema), or involved multiple organ systems (anaphylaxis).

Palforzia® is an oral immunotherapy indicated for the mitigation of allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanut. Palforzia® is approved for use in patients with a confirmed diagnosis of peanut allergy. Initial Dose Escalation may be administered to patients aged 4 through 7 years. Up-Dosing and Maintenance may be continued in patients 4 years of age and older. Palforzia® is to be used in conjunction with a peanut-avoidant diet. The mechanism of action of Palforzia® has not been established.

The intent of this policy is to communicate the medical necessity criteria for Peanut Immunotherapy (Palforzia®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA Peanut immunotherapy (Palforzia®) is approved when ALL of the following are met:

  1. Diagnosis of peanut allergy as documented by all of the following:
    1. Serum peanut-specific IgE level of greater than or equal to 0.35kUA/L; and
    2. Mean wheal diameter that is at least 3mm larger than the negative control on skin-prick testing for peanut; and
  2. Member does not have any of the following:
    1. History of eosinophilic esophagitis (EoE) or eosinophilic gastrointestinal disease; or
    2. History of severe or life-threatening episode(s) of anaphylaxis or anaphylactic shock within the past 2 months; or
    3. Severe or poorly controlled asthma; and
  3. One of the following:
    1. Member is 4 to 17 years of age and in the initial dose escalation phase of therapy; or
    2. Member is 4 years of age or older and in the up-dosing or maintenance phase of therapy; and
  4. Prescribed by or in consultation with an allergist/immunologist

Initial authorization duration: 12 months

REAUTHORIZATION CRITERIA Peanut immunotherapy (Palforzia®) is re-approved when prescribed by or in consultation with allergist/immunologist.

Reauthorization duration: 12 months


WARNING: ANAPHYLAXIS
  • PALFORZIA can cause anaphylaxis, which may be life-threatening and can occur at any time during PALFORZIA therapy.
  • Prescribe injectable epinephrine, instruct and train patients on its appropriate use, and instruct patients to seek immediate medical care upon its use. 
  • Do not administer PALFORZIA to patients with uncontrolled asthma. 
  • Dose modifications may be necessary following an anaphylactic reaction. 
  • Observe patients during and after administration of the Initial Dose Escalation and the first dose of each Up-Dosing level, for at least 60 minutes. 
  • PALFORZIA is available only through a restricted program called the PALFORZIA REMS.


Palforzia® (peanut immunotherapy) [package insert]. Brisbane, CA: Aimmune Therapeutics, Inc. July 2022. Available at: https://www.palforzia.com/static/pi_palforzia.pdf. Accessed February 13, 2024.

Wang, Julie MD. Peanut, tree nut, and seed allergy: Clinical Features.  UpToDate. Updated October 2023. Accessed February 13, 2024.​

612/18/202312/18/20244/1/2024 1:26 AMNo presence informationsrv_ppsgw_P
​Off-Label Use policy Rx.01.33
Palforzia®Peanut immunotherapy
359
  
4/1/2024Rx.01.183CommercialOyenusi, OluwadamilolaQ4-2023
Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as an unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than six weeks duration in the absence of infection or other identifiable causes.   The prevalence of IC/BPS in the United States is estimated to be 83,000 men and 1.2 million women.  Treatment should start with conservative therapies and progress to more aggressive therapies if symptom control is not adequate.  Medications, including amitriptyline, cimetidine, hydroxyzine and pentosan polysulfate are all considered second line treatments.

The mechanism of action of pentosan polysulfate sodium in IC/BPS is unknown. The compound is similar to low molecular weight heparin, and has anticoagulant and fibinolytic effects. It is thought to prevent solutes in the urine from irritating the bladder wall by binding to the mucosal membrane and acting as a buffer.  

Elmiron® is indicated for the relief of bladder pain or discomfort associated with interstitial cystitis.

The intent of this policy is to communicate the medical necessity criteria for pentosan polysulfate (Elmiron®) as provided under the member’s prescription drug benefit.

INITIAL CRITERIA: Pentosan polysulfate sodium (Elmiron®) is approved when ALL of the following are met:

  1. Diagnosis of interstitial cystitis/ bladder pain syndrome and BOTH of the following:
    1. Pain, pressure, or discomfort associated with lower urinary tract symptoms for 6 weeks or longer; and
    2. Absence of infection or other identifiable cause; and
  2. Inadequate response to conservative therapy (e.g., bladder training, pelvic floor rehab, biofeedback, etc.); and
  3. Member is 16 years of age or older; and 
  4. Inadequate response or inability to tolerate ONE of the following:
    1. Amitriptyline; or
    2. Cimetidine; or 
    3. Hydroxyzine

Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Pentosan polysulfate sodium (Elmiron®) is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 year


N/A
 Clemens JQ, Erickson DR, Varela NP, Lai HH. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2022;208(1):34-42. Available at: https://www.auanet.org/guidelines-and-quality/guidelines/diagnosis-and-treatment-interstitial-of-cystitis/bladder-pain-syndrome-(2022). Accessed February 13, 2024.

Elmiron® (pentosan polysulfate sodium) [prescribing information]. Titusville, NJ, Janssen Pharmaceuticals, Inc.; March 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f0ba651e-3d8a-11df-8fbe-119855d89593&type=display. Accessed February 13, 2024.

Rovner ES. Interstitial cystitis. Updated August 2022. Available at: http://emedicine.medscape.com/article/2055505-overview. Accessed February 13, 2024.​

912/18/202312/18/20244/1/2024 1:26 AMNo presence informationsrv_ppsgw_P
Off-Label Use Rx.01.33
Elmiron®pentosan polysulfate sodium
360
  
4/1/2024Rx.01.163CommercialOyenusi, OluwadamilolaQ4-2023
Psychosis is a frequent complication of Parkinson’s disease (PD), and it is characterized mainly by visual hallucinations and delusions. Hallucinations are the most common manifestation, affecting up to 40 percent of patients with PD, particularly those at an advanced stage of illness. The adverse effects of antiparkinson medications are probably the most important cause of psychosis in patients with PD. Other triggers include infection, delirium, dementia, and psychoactive medications.  

Management of psychosis in patients with PD involves identifying and treating the underlying causes and contributory factors, including general measures that are similar to the treatment of delirium. Stopping all potentially offending antiparkinsonian drugs is usually not an option for most patients, although dose reduction can frequently be accomplished with amelioration of hallucinations and little loss of drug-related benefit. ​​Carbidopa​/levodopa should be the last of a drug combination to be reduced, since it is the most effective antiparkinson agent and least likely to cause psychosis.

For patients with troublesome hallucinations or delusions despite antiparkinson medication adjustments, options include treatment with ​quetiapine, ​clozapine, or pimavanserin. The atypical neuroleptics clozapine and quetiapine may be helpful starting with low doses and incrementing slowly according to clinical response.  Since quetiapine is easier to use than clozapine (no monitoring required) and is often effective, it should be the treatment of first choice.

The mechanism of action of pimavanserin in the treatment of hallucinations and delusions associated with Parkinson's disease psychosis is unknown. However, the effect of pimavanserin could be mediated through a combination of inverse agonist and antagonist activity at serotonin 5-HT2A receptors and to a lesser extent at serotonin 5-HT2C receptors.  Pimvanaserin (Nuplazid®) is indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.

The intent of this policy is to communicate the medical necessity criteria for pimavanserin (Nuplazid®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Pimavanserin (Nuplazid®) is approved when ALL of the following are met:

  1. Diagnosis of hallucinations and delusions associated with Parkinson's disease; and
  2. Trial of dose adjustment or withdrawal of antiparkinsonian medications (anticholinergics, amantadine, dopamine agonists, COMT inhibitors, selegiline) prior to treatment with pimavanserin; and
  3. Inadequate response or inability to tolerate clozapine or quetiapine; and
  4. Member is 18 years of age or older

Initial Authorization duration: 6 months

 

REAUTHORIZATION CRITERIA: Pimavanserin (Nuplazid®) is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years


WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. NUPLAZID is not approved for the treatment of patients with dementia who experience psychosis unless their hallucinations and delusions are related to Parkinson’s disease.

Chahine L. Management of nonmotor symptoms in Parkinson disease. Updated November 2023. In: UpToDate, Connor RF (Ed), Wolters Kluwer. Accessed February 13, 2024.

Nuplazid® (pimavanserin) [package insert]. San Diego, CA. Acadia Pharmaceuticals, Inc. September 2023.  Available at: https://www.nuplazid.com/sites/nuplazid/files/pdf/NUPLAZID_Prescribing_Information.pdf. Accessed February 13, 2024. 
1312/18/202312/18/20244/1/2024 1:27 AMNo presence informationsrv_ppsgw_P
Off-Label Use Rx.01.33
Nuplazid®pimavanserin
362
  
4/1/2024Rx.01.233CommercialOyenusi, OluwadamilolaQ4-2023
Congenital sucrase-isomaltase deficiency is a disorder that effects a patient’s ability to digest sucrose and maltose. Congenital sucrase-isomaltase deficiency is usually identified in infancy when babies start to consume fruits, juices, and grains. These children will typically experience stomach cramps, bloating, diarrhea, and excess gas production. It can also lead to failure to gain weight, malnutrition, and failure to thrive. 

Sucraid® (sacrosidase) is an enzyme replacement therapy indicated for the treatment of genetically determined sucrase deficiency, which is part of congenital sucrase-isomaltase deficiency.

The intent of this policy is to communicate the medical necessity criteria for Sucraid® (sacrosidase) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Sacrosidase (Sucraid®) is approved when all of the following are met:

  1. Diagnosis of sucrase deficiency (which is part of congenital sucrose-isomaltase deficiency [CSID]); and
  1. Prescribed by or in consultation with gastroenterologist or geneticist

Initial Authorization duration: 2 years


REAUTHORIZATION CRITERIA: Sacrosidase (Sucraid®) is re-approved when there is positive clinical response to therapy.

Reauthorization duration: 2 years


N/A
Congenital sucrase-isomaltase deficiency. US National Library of Medicine website. Updated February 14, 2023. Available from: https://medlineplus.gov/genetics/condition/congenital-sucrase-isomaltase-deficiency/. Accessed February 13, 2024.

Sucraid® (sacrosidase) [package insert]. Kirkland, WA: QOL Medical, LLC; May 2023. Available from: https://www.sucraid.com/wp-content/uploads/2019/12/SucPI_R0219.pdf. Accessed February 13, 2024.​

512/18/202312/18/20244/1/2024 1:27 AMNo presence informationsrv_ppsgw_P
Rx.01.33 Off Label Use
Rx.01.221 Drugs Exceeding Claim Dollar Limit Threshold

Sucraid®sacrosidase
363
  
4/1/2024Rx.01.127CommercialOyenusi, OluwadamilolaQ4-2023
Short bowel syndrome (SBS) is a malabsorptive condition most commonly caused by resection of the small intestine.  It is defined not by the length resected bowel, but upon degree of intestinal dysfunction (ie significant malabsorption of both macronutrients and micronutrients). 

Teduglutide is an analog of naturally occurring human glucagonlike peptide-2, a peptide secreted by L-cells of the distal intestine. Glucagonlike peptide-2 is known to increase intestinal and portal blood flow and inhibit gastric acid secretion. Teduglutide binds to the glucagonlike peptide-2 receptors located in intestinal subpopulations of enteroendocrine cells, subepithelial myofibroblasts, and enteric neurons of the submucosal and myenteric plexus. Activation of these receptors results in the local release of multiple mediators, including insulin-like growth factor-1, nitric oxide, and keratinocyte growth factor.

Teduglutide (Gattex®) is indicated for the treatment of adults and pediatric patients 1 year of age and older with Short Bowel Syndrome (SBS) who are dependent on parenteral support.

The intent of this policy is to communicate the medical necessity criteria for teduglutide (Gattex®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Teduglutide (Gattex®) is approved when ALL of the following are met:

  1. Diagnosis of Short Bowel Syndrome (SBS) (defined as a member left with <200 cm of functional small bowel); and
  2. Currently receiving parenteral support at least three times per week for at least 12 consecutive months; and
  3. Prescribed by or in consultation with a gastroenterologist; and
  4. Member is 1 year of age or older

Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Teduglutide (Gattex®) is re-approved when BOTH of the following are met:

  1. Documentation of reduction in parenteral support from baseline (prior to initiation of teduglutide therapy); and
  2. Prescribed by or in consultation with a gastroenterologist

 Reauthorization duration: 2 years


N/A
DiBaise JK. Pathophysiology of short bowel syndrome. UpToDate. Updated August 2023. Available at: https://www.uptodate.com. Accessed February 13, 2024.

Gattex® (teduglutide) [prescribing information]. Lexington, MA. Shire-NPS Pharmaceuticals, Inc. October 2022. Available at: https://www.shirecontent.com/PI/PDFS/Gattex_USA_ENG.pdf .  Accessed February 13, 2024. ​

1212/18/202312/18/20244/1/2024 1:27 AMNo presence informationsrv_ppsgw_P
Off-Label Use policy Rx.01.33
Gattex®teduglutide
364
  
4/1/2024Rx.01.201CommercialOyenusi, OluwadamilolaQ4-2023
​Carcinoid syndrome is a constellation of symptoms mediated by various hormones secreted by some carcinoid tumors. Two of the most common manifestations are flushing and diarrhea, which are associated with elevations in serum serotonin or its metabolite urinary 5-hydroxyindoleacetic acid (5-HIAA). More than 90 percent of patients with carcinoid syndrome have metastatic disease, typically involving the liver, with primary tumors in the distal small intestine or proximal colon (midgut).

Telotristat, the active metabolite of telotristat ethyl, is a tryptophan hydroxylase (TPH) inhibitor, which mediates the rate limiting step in serotonin biosynthesis. Serotonin plays a role in mediating secretion, motility, inflammation, and sensation of the gastrointestinal tract, and is over-produced in patients with carcinoid syndrome. Decreased production of peripheral serotonin by telotristat and telotristat ethyl through the inhibition of tryptophan hydroxylase results in a reduction of the frequency of carcinoid syndrome diarrhea.

Telotristat ethyl (Xermelo®) is indicated for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy.

The intent of this policy is to communicate the medical necessity criteria for telotristat ethyl (Xermelo®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Telotristat (Xermelo®) is approved when ALL of the following are met:

  1. Diagnosis of carcinoid syndrome diarrhea; and
  2. Member is 18 years of age or older; and
  3. Diarrhea is inadequately controlled by a stable dose of somatostatin analog (SSA) therapy (e.g., octreotide [Sandostatin, Sandostatin LAR], lanreotide [Somatuline Depot]) for at least 3 months; and
  4. Used in combination with SSA therapy; and
  5. Prescribed by or in consultation with one of the following:
    1. Oncologist
    2. Endocrinologist
    3. Gastroenterologist

Initial authorization duration:  12 months

REAUTHORIZATION CRITERIA: Telotristat (Xermelo®) is reapproved when BOTH of the following are met:

  1. Documentation of positive clinical response to Xermelo® therapy; and
  2. Xermelo® will continue to be used in combination with SSA therapy (e.g., octreotide [Sandostatin, Sandostatin LAR], lanreotide [Somatuline Depot])

Reauthorization duration: 2 years


N/A

Xermelo (telotristat ethyl) [package insert]. The Woodlands, TX. Lexicon Pharmaceuticals, Inc. September 2022. Available at: https://documents.tersera.com/xermelo/XermeloPrescribingInformation.pdf. Accessed February 13, 2024.

Kulke MH, Hörsch D, Caplin ME, et al. Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome. J Clin Oncol 2017; 35(1): 14-23.

Strosber JR. Treatment of carcinoid syndrome. Uptodate. Last updated October 2023. Available at: https://www.uptodate.com/contents/treatment-of-the-carcinoid-syndrome?search=Treatment%20of%20carcinoid%20syndrome&source=search_result&selectedTitle=1~77&usage_type=default&display_rank=1. Accessed February 13, 2024.

812/18/202312/18/20244/1/2024 1:27 AMNo presence informationsrv_ppsgw_P
Off-Label Use Rx.01.33
Xermelo®telotristat
365
  
4/1/2024Rx.01.235CommercialOyenusi, OluwadamilolaQ4-2023
Fatty acid oxidation disorders (FAOD) are inborn errors of metabolism due to disruption of either the fatty acid transport using the carnitine transport pathway or mitochondrial beta oxidation. FAODs present differently depending upon the specific disorder, but all ultimately require similar treatment. 

FAOD presenting in neonates generally show severe symptoms, including cardiomyopathy. During infancy and childhood, patients experience liver dysfunction and hypoketotic hypoglycemia. After adolescence, episodic rhabdomyolysis is sometimes seen. 

General treatment of FAODs include avoidance of fasting, aggressive treatment during illness, and supplementation of carnitine, if necessary. Long chain fatty acid oxidation disorders differ by requiring a fat-restricted diet and supplementation of medium chain triglyceride oil and often docosahexaenoic acid.

Dojolvi™ (triheptanoin) is a medium-chain triglyceride indicated as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD).



The intent of this policy is to communicate the medicalnecessity criteria for triheptanoin (Dojolvi™) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Triheptanoin (DojolviTM) is approved when BOTH of the following are met:

  1. Diagnosis of molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD); and
  2. Will be used as a source of calories and fatty acids; and
  3. Not used with any other medium-chain triglyceride (MCT) product; and
  4. Prescribed by or in consultation with a clinical specialist knowledgeable in appropriate disease-related dietary management (e.g., geneticist, cardiologist, gastroenterologist, etc.)

Initial Authorization duration: 2 years

 

REAUTHORIZATION CRITERIA: Triheptanoin (DojolviTM) is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years


N/A
Dojolvi™ (triheptanoin) [package insert]. Novato, Ca. Ultragenyx Pharmaceutical Inc. October 2023. Available from: accessdata.fda.gov/drugsatfda_docs/label/2020/213687s00lbl.pdf. Accessed February 13, 2024.

Merritt JL 2nd, Norris M, Kanungo S. Fatty acid oxidation disorders. Ann Transl Med. 2018;6(24):473. Doi:10.21037/atm.2018.10.57. Accessed February 13, 2024.​

512/18/202312/18/20244/1/2024 1:27 AMNo presence informationsrv_ppsgw_P
Rx.01.33 Off Label Use
Dojolvi™triheptanoin
366
  
4/1/2024Rx.01.276CommercialOyenusi, OluwadamilolaQ4-2023
​Rett syndrome is a rare genetic neurological disorder that leads to severe impairments and affects nearly every aspect of the child’s life: their ability to speak, walk, eat, and even breathe easily. Rett syndrome is usually recognized in children between 6 to 18 months as they begin to miss developmental milestones or lose abilities they had gained. After a brief period of initially normal development, affected patients experience loss of speech and purposeful hand use, stereotypic hand movements, and gait abnormalities. Additional manifestations include deceleration of head growth, seizures, autistic features, and breathing abnormalities. Rett syndrome is caused by mutations on the X chromosome on a gene called MECP2.

The mechanism by which trofinetide exerts therapeutic effects in patients with Rett syndrome is unknown. However, actions could include anti-inflammatory, anti-oxidant, and trophic effects that stabilize dendritic morphology, synaptic protein synthesis, and neuronal signaling.

Daybue is indicated for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older.

The intent of this policy is to communicate the medical necessity criteria for trofinetide (Daybue™) as provided under the member's prescription drug benefit. 
INITIAL CRITERIA: Trofinetide (Daybue™) is approved when all of the following are met:
  1. Diagnosis of Rett syndrome; and
  2. One of the following:
    1. Presence of ALL of the following clinical signs and symptoms:
      1. A pattern of development, regression, then recovery or stabilization; and
      2. Partial or complete loss of purposeful hand skills such as grasping with fingers, reaching for things, or touching things on purpose; and
      3. Partial or complete loss of spoken language; and
      4. Repetitive hand movements, such as wringing the hands, washing, squeezing, clapping, or rubbing; and
      5. Gait abnormalities, including walking on toes or with an unsteady, wide-based, stiff-legged gait; or
    2. Molecular genetic testing confirms mutations in the MECP2 gene; and
  3. Member is 2 years of age or older; and
  4. Prescribed by or in consultation with one of the following:
    1. Geneticist; or
    2. Pediatrician; or
    3. neurologist
Initial authorization duration: 1 year 

REAUTHORIZATION CRITERIA: Trofinetide (Daybue™) is re-approved when BOTH of the following are met:
  1. Documentation of positive clinical response to therapy as evidenced by an improvement in clinical signs and symptoms from baseline (e.g., hand behavior, walking/standing, speech, quality of life); and
  2. Prescribed by or in consultation with one of the following:
    1. Geneticist; or
    2. Pediatrician; or
    3. neurologist
Reauthorization duration: 1 year​

N/A
Schultz RJ. Rett syndrome: Treatment and prognosis. UpToDate. April 2023. Available at: https://www.uptodate.com. Accessed February 13, 2024.

Daybue™ (trofinetide) [package insert]. San Diego, CA: Acadia Pharmaceuticals Inc. March 2023. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217026s000lbl.pdf. Accessed February 13, 2024.

“What Is Rett Syndrome?" International Rett Syndrome Foundation, 21 Apr. 2023, www.rettsyndrome.org/about-rett-syndrome/what-is-rett-syndrome/. Accessed February 13, 2024.

212/18/202312/18/20244/1/2024 1:28 AMNo presence informationsrv_ppsgw_P
​Rx.01.33 Off Label Use​
Daybue™trofinetide
372
  
4/1/2024Rx.01.285CommercialOyenusi, OluwadamilolaQ4-2023
Patients with established cardiovascular disease (CVD) have a high risk of subsequent CVD events, including myocardial infarction (MI), stroke, and death.  Therapeutic lifestyle changes, which include increased physical activity, dietary modification/weight loss, and smoking cessation are of proven benefit and improve outcomes beginning within a matter of weeks. In addition, adjunctive drug therapies of proven benefit include statins and aspirin, whose benefits are at least additive.

The mechanism of action of colchicine in the prevention of major cardiovascular events is not understood. However, it is known that colchicine disrupts cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules and consequently prevents the activation, degranulation, and migration of neutrophils. Colchicine may also interfere with the intracellular assembly of the inflammasome complex in neutrophils and monocytes that mediates activation of interleukin-1β. These anti-inflammatory effects are consistent with clinical data demonstrating that colchicine reduces high sensitivity C- reactive protein (hs-CRP).

Lodoco is indicated to reduce the risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease.

The intent of this policy is to communicate the medical necessity criteria for Colchicine (Lodoco) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Colchicine (Lodoco) is approved when all of the following are met:

  1. Diagnosis of cardiovascular disease (CV); and
  2. Used for the secondary prevention of CV disease (e.g., very high-risk patients); and
  3. Member is 18 years of age or older; and
  4. Member is on guideline therapy management for multiple risk factors (e.g., dyslipidemia, hypertension, hyperglycemia) associated with CV disease

 

Initial authorization duration: 6 months

 

REAUTHORIZATION CRITERIA: Colchicine (Lodoco) is re-approved when documentation is provided of positive clinical response to therapy

 

Reauthorization duration: 6 months


N/A
Hennekens CH, Lopez-Sendon J. Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk. July 2023. In: UpToDate, Connor RF (Ed), Wolters Kluwer. Accessed February 15, 2024.

Lodoco (colchicine) [prescribing information]. Parsippany, NJ: AGEPHA Pharma USA, LLC. June 2023. Available from: https://lodoco.com/. Accessed February 15, 2024. 

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Off-Label Use Rx.01.33
Brand NameGeneric Name
​Lodoco

Colchicine

LODOCO       TAB 0.5MGCOLCHICINE (CARDIOVASCULAR) TAB 0.5 MG
374
  
4/1/2024Rx.01.286CommercialOyenusi, OluwadamilolaQ4-2023
Anemia (defined as a hemoglobin [Hb] level <13 g/dL in men or <12 g/dL in women) is a common complication of chronic kidney disease (CKD). The anemia in CKD occurs as a normocytic anemia, meaning the red blood cells are a normal size but there is simply a low number of them. This occurs because the kidneys are responsible for producing a hormone called erythropoietin, which prompts the body to produce red blood cells. Patients with CKD cannot make enough erythropoietin; therefore, low erythropoietin levels cause a low red blood cell count, leading to chronic anemia. 

The risk for anemia increases with advancing stages of disease, with an estimated prevalence of 17% in Stage 3, 50% in Stage 4, and at least 54% in Stage 5 (end-stage renal disease [ESRD]). In individuals with CKD, severe anemia can increase the chance of developing cardiovascular (CV) problems because the heart gets less oxygen than normal and must work harder to pump enough red blood cells to the organs and tissues. These patients are also at an increased risk for complications due to strokes. Cardiovascular disease is the leading cause of death in dialysis-dependent (DD) patients. 

Erythropoietin-stimulating agents (ESAs) are the current standard of care (SOC) for treating anemia in CKD, but they are largely reserved for the DD patient population, given their parenteral administration, storage requirements, and CV safety concerns. 

Daprodustat is a reversible inhibitor of HIF-PH1, PH2 and PH3 (IC50 in the low nM range). This activity results in the stabilization and nuclear accumulation of HIF-1α and HIF-2α transcription factors, leading to increased transcription of the HIF-responsive genes, including erythropoietin.

JESDUVROQ is a hypoxia-inducible factor prolyl hydroxylase (HIF PH) inhibitor indicated for the treatment of anemia due to chronic kidney disease in adults who have been receiving dialysis for at least four months. (1) Limitations of Use Not shown to improve quality of life, fatigue, or patient well-being. Not indicated for use: 
  • As a substitute for transfusion in patients requiring immediate correction of anemia. 
  • In patients not on dialysis.
The intent of this policy is to communicate the medical necessity criteria for daprodustat (Jesduvroq®) as provided under the member's prescription drug benefit. 

 INITIAL CRITERIA: Daprodustat (Jesduvroq™) is approved when ALL of the following are met:

  1. Documentation is provided of chronic kidney disease (CKD); and
  2. Member is 18 years of age or older; and
  3. Member has been on dialysis for at least 4 months; and
  4. Adequate iron stores confirmed by one of the following:
    1. Member's ferritin level is greater than 100 mcg/L; or
    2. Member's transferrin saturation (TSAT) is greater than 20%; and
  5. Pretreatment hemoglobin level of 8 to 11.5 g/dL; and
  6. Inadequate response or inability to tolerate one of the following:
    1. Retacrit
    2. Procrit
    3. Aranesp; and
  7. Prescribed by or in consultation with one of the following:
    1. Hematologist
    2. Nephrologist; and
  8. Member is not on concurrent treatment with an erythropoietin stimulating agent [ESA] (e.g., Aranesp, Epogen, Procrit)

 

Initial authorization duration: 6 months

 

REAUTHORIZATION CRITERIA: Daprodustat (Jesduvroq™) is reapproved when ALL of the following are met:

  1. Documentation is provided of a positive clinical response to therapy as evidenced by a hemoglobin level of 10-11 g/dL; and
  2. Adequate iron stores confirmed by one of the following:
    1. Member's ferritin level is greater than 100 mcg/L; or
    2. Member's transferrin saturation (TSAT) is greater than 20%; and
  3. Member is not on concurrent treatment with an erythropoietin stimulating agents [ESA] (e.g., Aranesp, Epogen, Procrit)

 

Reauthorization duration: 2 years


WARNING: INCREASED RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, and THROMBOSIS OF VASCULAR ACCESS. 

  • JESDUVROQ increases the risk of thrombotic vascular events, including major adverse cardiovascular events (MACE). 
  • Targeting a hemoglobin level greater than 11 g/dL is expected to further increase the risk of death and arterial venous thrombotic events, as occurs with erythropoietin stimulating agents (ESAs), which also increase erythropoietin levels. 
  • No trial has identified a hemoglobin target level, dose of JESDUVROQ, or dosing strategy that does not increase these risks. 
  • Use the lowest dose of JESDUVROQ sufficient to reduce the need for red blood cell transfusions. 
National Institute of Diabetes and Digestive and Kidney Diseases. Anemia in chronic kidney disease. Last reviewed September 2020. Available at: https://www.niddk.nih.gov/health-information/kidney-disease/anemia. Accessed February 14, 2024

Jesduvroq (daprodustat) [prescribing information]. Durham, NC: GlaxoSmithKline. August 2023. Available at: JESDUVROQ (daprodustat) tablets (gskpro.com). Accessed February 14, 2024. 
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Rx.01.33 Off Label Use
Jesduvroq™ daprodustat
375
  
4/1/2024Rx.01.287CommercialOyenusi, OluwadamilolaQ4-2023
FOP, or myositis ossificans progressiva, is an ultra-rare, genetic connective tissue disorder characterized by severe, progressive development of bone in areas outside of the skeleton (heterotopic ossification; HO), such as the ligaments, tendons, and muscles. The hallmark symptom of FOP is malformation of the big toes at birth. Episodes of painful soft tissue swelling, known as flare-ups, begin during the first decade of life, and these are often precipitated by soft tissue injury, intramuscular injections, viral infections, or falls. These flare-ups may lead to extraskeletal HO, which progresses throughout life. Over time, HO eventually leads to stiffness in affected areas, limited movement, and eventual ankylosis (fusion) of affected joints. Many individuals with FOP are confined to a wheelchair by their 30s, requiring lifelong assistance with activities of daily living. The estimated median lifespan of individuals with FOP is 56 years; death is often due to cardiorespiratory failure as a result of severe restriction of the chest wall. 

FOP is caused by mutations in the activin A receptor type 1 gene (ACVR1), which encodes a bone morphogenetic protein (BMP) type I receptor that is important during the formation of the skeleton in the embryo and the repair of the skeleton following birth. The mutation in the ACVR1 gene increases BMP signaling, resulting in the formation of heterotopic bone. Approximately 97% of patients with FOP have the same ACVR1 point mutation (arginine to histidine [R206H]), which is considered classic FOP. Most cases of FOP occur sporadically; however, in a small number of cases, the condition is inherited in an autosomal dominant pattern. The diagnosis of FOP may be confirmed by clinical evaluation, characteristic physical findings, and sequencing of the ACVR1 gene. 

In patients with FOP, abnormal bone formation, including heterotrophic ossification (HO), is driven by a gain-of-function mutation in the bone morphogenetic protein (BMP) type I receptor ALK2 (ACVR1). Palovarotene is an orally bioavailable retinoic acid receptor agonist, with particular selectivity at the gamma subtype of RAR. Through binding to RARγ, palovarotene decreases the BMP/ALK2 downstream signaling pathway by inhibiting the phosphorylation of SMAD1/5/8, which reduces ALK2/SMAD-dependent chondrogenesis and osteocyte differentiation resulting in reduced endochondral bone formation.

SOHONOS is a retinoid indicated for reduction in the volume of new heterotopic ossification in adults and children aged 8 years and older for females and 10 years and older for males with fibrodysplasia ossificans progressiva (FOP)
The intent of this policy is to communicate the medical necessity criteria for palovarotene (Sohonos®) as provided under the member's prescription drug benefit. 

 INITIAL CRITERIA: Palovarotene (Sohonos) is approved when all of the following are met:

  1. Diagnosis of Fibrodysplasia Ossificans Progressiva (FOP); and
  2. Molecular genetic testing confirms mutations in the ACVR1 gene; and
  3. One of the following:
    1. Both of the following:
      1. Member is female; and
      2. Member is 8 years of age or older; or
    2. Both of the following:
      1. Member is male; and
      2. Member is 10 years of age or older; and
  4. Prescribed by or in consultation with one of the following:
    1. Geneticist; or
    2. Orthopedic physician

 

Initial authorization duration: 12 months

 

REAUTHORIZATION CRITERIA: Palovarotene (Sohonos) is re-approved if documentation is provided that member demonstrates positive clinical response to therapy (e.g., reduction in volume in new abnormal bone growth)

 

Reauthorization duration: 12 months


WARNING: EMBRYO-FETAL TOXICITY and PREMATURE EPIPHYSEAL CLOSURE IN GROWING PEDIATRIC PATIENTS 
Embryo-Fetal Toxicity SOHONOS is contraindicated in pregnancy. SOHONOS may cause fetal harm. Because of the risk of teratogenicity and to minimize fetal exposure, SOHONOS is to be administered only if conditions for pregnancy prevention are met. 
Premature Epiphyseal Closure Premature epiphyseal closure occurs in growing pediatric patients treated with SOHONOS, close monitoring is recommended 
National Organization for Rare Disorders. Fibrodysplasia ossificans progressive. Updated August 21, 2023. Available at: https://rarediseases.org/rare-diseases/fibrodysplasia-ossificans-progressiva/. Accessed February 14, 2024
Sohonos (palovarotene) [prescribing information]. Cambridge, MA: Ipsen Biopharmaceuticals, Inc. August 2023. Available at: Microsoft Word - pi-mg-fda-comments-15aug2023-combined-rev 17Aug2023 (d2rkmuse97gwnh.cloudfront.net). Accessed February 14, 2024
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Rx.01.33 Off-Label Use
Sohonos® palovarotene
382
  
7/1/2024Rx.01.158CommercialOyenusi, OluwadamilolaQ1-2024

Allergic rhinitis is a persistent condition that typically requires ongoing therapy.  Allergen avoidance along with pharmacologic therapy with nasal corticosteroids and oral antihistamines are standard management.  Allergen immunotherapy is reserved for severe or refractory cases.  Sublingual immunotherapy involves the application of the allergen to the sublingual tissue.  In the case of Odactra™, Oralair®, Grastek®, and Ragwitek®, the allergen is in a sublingual tablet which is self-administered, after the first dose.

The exact mechanism of sublingual allergen immunotherapy has not been fully elucidated.  Allergen extracts given sublingually are primarily taken up by dendritic cells in the mucosa and presented to T cells in the draining lymph nodes. Likely mechanisms of action include activation of T regulatory cells and downregulation of mucosal mast cells. Within the oral and sublingual mucosa, effector cells, such as mast cells, are less numerous, which may account for the lower rates of adverse systemic allergic reactions seen with sublingual immunotherapy.

Timothy grass pollen allergen extract (Grastek®) is indicated as immunotherapy for the treatment of grass pollen-induced allergic rhinitis with or without conjunctivitis confirmed by positive skin test or in vitro testing for pollen-specific IgE antibodies for Timothy grass or cross-reactive grass pollens in persons 5 through 65 years of age.

Short ragweed pollen allergen extract (Ragwitek®) is indicated as immunotherapy for the treatment of short ragweed pollen-induced allergic rhinitis, with or without conjunctivitis, confirmed by positive skin test or in vitro testing for pollen-specific IgE antibodies for short ragweed pollen in individuals 5 through 65 years of age.

Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue Grass mixed pollens allergen extract (Oralair®) is indicated as immunotherapy for the treatment of grass pollen-induced allergic rhinitis with or without conjunctivitis confirmed by positive skin test or in vitro testing for pollen-specific IgE antibodies for any of the five grass species contained in this product in persons 10 through 65 years of age. 

Dermatophagoides farinae or Dermatophagoides pteronyssinus house dust mite allergen extract (Odactra™) is indicated as immunotherapy for house dust mite (HDM)-induced allergic rhinitis, with or without conjunctivitis, confirmed by positive in vitro testing for IgE antibodies to Dermatophagoides farinae or Dermatophagoides pteronyssinus house dust mites, or by positive skin testing to licensed house dust mite allergen extracts. Odactra™ is approved for use in individuals12 through 65 years of age.


The intent of this policy is to communicate the medical necessity criteria for house dust mite allergen extract (Odactra™), grass pollen allergen extract-5 grass (Oralair®), grass pollen allergen extract-timothy grass (Grastek®), and short ragweed pollen allergen extract (Ragwitek®) as provided under the member’s prescription drug benefit.

INITIAL CRITERIA: Odactra™, Oralair®, Grastek® or Ragwitek® is approved when ALL of the following are met:

  1. FDA approved indication; and
  2. Patient has a positive skin test or in vitro test for ONE of the listed pollen-specific IgE antibodies:
    1. Timothy Grass or cross-reactive grass pollens (GRASTEK® only); or
    2. Any of the five grass species including sweet vernal, orchard perennial rye, timothy or Kentucky blue grass mixed pollens (ORALAIR® only); or
    3. Short ragweed pollen (RAGWITEK® only); or
    4. Dermatophagoides farina or Dermatophagoides pteronyssinus house dust mites (ORDACTRA™ only); and
  3. Prescribed by or in consultation with allergist or immunologist and
  4. ONE of the following:
    1. For Grastek, member is between 5 to 65 years of age; or
    2. For Odactra, member is between 12 to 65 years of age; or
    3. For Oralair, member is between 5 to 65 years of age; or
    4. For Ragwitek, member is between is 5 to 65 years of age; and
  5. Patient does not have any of the following:
    1. Severe, unstable or uncontrolled asthma; or
    2. History of eosinophilic esophagitis; and
  6. Patient has had an inadequate response or inability to tolerate BOTH of the following:
    1. Intranasal corticosteroid; and
    2. Antihistamine


Initial Authorization duration: 1 year 

REAUTHORIZATION CRITERIA: Odactra™, Oralair®, Grastek® or Ragwitek® is re-approved when ALL of the following are met:

  1. Use in the age group supported by FDA labeling; and
  2. Prescribed by or in consultation with allergist or immunologist; and
  3. Patient has experienced improvement in the symptoms of their allergic rhinitis OR a decrease in the number of medications needed to control allergy symptoms 

Reauthorization duration: 1 year 


Severe allergic reactions:

Odactra™, Grastek®, Oralair® and Ragwitek® can cause life-threatening allergic reactions such as anaphylaxis and severe laryngopharyngeal restriction. 

Do not administer Odactra™, Grastek®, Oralair® and Ragwitek® to patients with severe, unstable or uncontrolled asthma. Observe patients in the office for at least 30 minutes following the initial dose.

Prescribe auto-injectable epinephrine, instruct and train patients on its appropriate use, and instruct patients to seek immediate medical care upon its use.

Odactra™, Grastek®, Oralair® and Ragwitek® may not be suitable for patients with certain underlying medical conditions that may reduce their ability to survive a serious allergic reaction.

Odactra™, Grastek®, Oralair® and Ragwitek® may not be suitable for patients who may be unresponsive to epinephrine or inhaled bronchodilators, such as those taking beta-blockers. 


Creticos PS. Sublingual immunotherapy (SCIT) for allergic rhinoconjunctivitis and asthma. UpToDate. Available at: http://www.uptodate.com/contents/sublingual-immunotherapy-for-allergic-rhinoconjunctivitis-and-asthma. Accessed April 17, 2024.

De Shazo RD, Kemp SF. Pharmacotherapy of allergic rhinitis. UpToDate. Available at: https://www.uptodate.com/contents/pharmacotherapy-of-allergic-rhinitis?search=pharmacotherapy-of-allergic-rhinitis.&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1. Accessed April 17, 2024.

Grastek® (Timothy grass pollen allergen extract) [package insert]. Whitehouse Station NJ. Merck and Co, Inc. December 2019. Accessed April 17, 2024.

Odactra™ (and house dust mite allergen extract) [package insert]. Whitehouse Station NJ. Merck and Co, Inc. January 2023. Available from: https://www.odactra.com/assets/pdf/odactra-full-pi.pdf. Accessed April 17, 2024.

Oralair® (Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue Grass mixed pollens allergen extract) [package insert]. Lenoir NC. Greer Laboratories, Inc. November 2018. Accessed April 17, 2024.

Ragwitek® (short ragweed pollen allergen extract) [package insert]. Whitehouse Station NJ. Merck and Co, Inc. April 2021. Accessed April 17, 2024. 


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Rx.01.33  Off- Label Use 
Brand NameGeneric Name
Grastek®grass pollen allergen extract-timothy grass 
Oralair®grass pollen allergen extract-5 grass
Ragwitek®short ragweed pollen allergen extract
Odactra™house dust mite allergen extract

NANA
383
  
7/1/2024Rx.01.216CommercialOyenusi, OluwadamilolaQ1-2024

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of the neuromuscular junction. LEMS is associated with reduced acetylcholine (ACh) release from the presynaptic nerve terminals. Antibodies directed against the voltage-gated calcium channel (VGCC) interfere with the normal calcium flux required for the release of ACh from the presynaptic nerve terminal. The most common symptoms of LEMS include proximal muscle weakness, fatigue, autonomic symptoms such as dry mouth, sluggish pupillary light response, erectile dysfunction in men, and reduced tendon reflexes. LEMS patients can be divided into two groups: patients with LEMS associated with underlying malignancy (paraneoplastic LEMS) and those without malignancy (non-paraneoplastic LEMS). For patients with paraneoplastic LEMS, treatment of malignancy may be the only intervention necessary to produce improvement in neurologic symptoms of LEMS.

Amifampridine (Firdapse®) is broad spectrum potassium channel blocker indicated for the treatment of LEMS in adults and pediatric patients 6 years of age and older. It blocks presynaptic voltage-gated potassium channels, prolonging the duration of the presynaptic action potential, lengthening the opening time of the VGCC, and increasing the presynaptic calcium levels. The increased calcium levels lead to an increase in the amount of ACh released. ACh then binds to muscle receptors and results in improved muscle function.    


The intent of this policy is to communicate the medical necessity criteria for amifampridine (Firdapse®) as provided under the member's prescription drug benefit

INITIAL CRITERIA: Amifampridine (Firdapse®) is approved when ALL of the following are met:

  1. Member has a diagnosis of Lambert-Eaton myasthenic syndrome; and
  2. Member is 6 years of age or older and
  3. Neurological symptoms persist after treatment of malignancy when malignancy is present; and
  4. Documentation of symptomatic LEMS that interfere with daily functions (e.g., difficulty climbing stairs, walking up steep hills); and
  5. Prescribed by or in consultation with a neurologist; and
  6. Member does not have history of seizures

Initial authorization duration: 3 months 

CONTINUATION CRITERIA: Amifampridine (Firdapse®) is re-approved when there is documentation of positive clinical response to therapy (e.g., improvement in dynamometry, Timed 25-Foot Walk Test, Timed Up and Go Test)
Reauthorization duration: 2 years


None

Firdapse® (amifampridine) [prescribing information]. Coral Gables, FL: Catalyst Pharmaceuticals, Inc.  September 2022. Available at: https://www.firdapse.com/pdfs/firdapse-pi.pdf. Accessed April 17, 2024.

Titulaer MJ, Lang B, Verschuuren JJGM. Lambert-Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies. Lancet Neurol. 2011[a]; 10:1098-1107.

Weinberg DH. Lambert-Eaton myasthenic syndrome: Clinical features and diagnosis. UpToDate Web site. Updated March 2023. www.uptodate.com. Accessed April 17, 2024.


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Rx.01.33 Off-Label Use
Brand NameGeneric Name
Firdapse®amifampridine phosphate

NANA
384
  
7/1/2024Rx.01.225CommercialOyenusi, OluwadamilolaQ1-2024

Diabetic foot ulcers are a prevalent complication of diabetes mellitus and represent major causes of morbidity and mortality. 15% of all diabetic individuals are affected by foot ulcers during their lifetime and 15-20% of those patients go on to need an amputation. Risk factors for development of diabetic foot ulcers include neuropathy, peripheral vascular disease, and poor glycemic control. Peripheral neuropathy results in patient loss of sensation and can exacerbate the development of ulcerations. Peripheral vascular disease can lead foot tissues to become ischemic. Many wounds go unnoticed and worsen through repetitive pressure because patients are unable to detect trauma to their lower extremities.  Multidisciplinary treatment today includes: surgical debridement, dressings promoting a moist wound environment, wound off-loading, vascular assessment, treatment of active infection, and glycemic control.

Regranex® gel is a recombinant human platelet-derived growth factor that promotes cellular proliferation and angiogenesis and thereby improve ulcer healing. Regranex® gel is indicated for the treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply. Regranex® gel is indicated as an adjunct to, and not a substitute for, good ulcer care practices.


The intent of this policy is to communicate the medical necessity criteria for becaplermin (Regranex®) gel as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Becaplermin (Regranex®) gel is approved when BOTH of the following are met:

  1. Member has a lower extremity diabetic neuropathic ulcer; and
  2. Treatment will be given in combination with ulcer wound care (e.g., debridement, infection control, and/or pressure relief)

Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Becaplermin (Regranex®) gel is re-approved when ONE of the following is met:

  1. Documentation of lower extremity diabetic neuropathic ulcer at a different treatment site; or
  2. Documentation of continued need for treatment beyond 6 months

Reauthorization duration: 6 months


None

Pendsey, S. Understanding diabetic foot. Int J Diabetes Dev Ctries 2010; 30:75-9. Accessed April 17, 2024.

Armstrong, D., J de Asla, R. Management of diabetic foot ulcers. UpToDate. March 2023. Available from: https://www.uptodate.com/contents/management-of-diabetic-foot-ulcers?search=diabetic%20foot%20ulcer&source=search_result&selectedTitle=1~61&usage_type=default&display_rank=1. Accessed April 17, 2024.

Regranex® (becaplermin gel) [prescribing information]. Fort Worth, TX: Smith & Nephew, Inc. December 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fd2c7d21-7b07-4ab3-8983-816ab3223771. Accessed April 17, 2024.


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Rx.01.33 Off Label Use 
Brand nameGeneric name
Regranex®Becaplermin

NANA
385
  
7/1/2024Rx.01.203CommercialOyenusi, OluwadamilolaQ1-2024

Systemic lupus erythematosus (SLE) is an autoimmune disorder that is very heterogeneous with respect to its severity and the organs affected. Approximately 1.5 million Americans, primarily women of childbearing age, have a form of lupus. SLE represents approximately 70% of all lupus cases. Common clinical manifestations of SLE include pain, extreme fatigue, hair loss, cognitive issues, rashes (often the classic “butterfly rash”), arthritis and arthralgias. More severe clinical manifestations include renal, hematologic, or central nervous system involvement. SLE is often associated with relapses (which can be acute or chronic) and remissions.

Lupus nephritis (LN) is a form of glomerulonephritis that constitutes one of the most severe organ manifestation of systemic lupus erythematosus (SLE). Most patients with SLE who develop LN do so within 5 years of an SLE diagnosis and in many cases, LN is the presenting manifestation resulting in the diagnosis of SLE. Treatment of LN usually involves immunosuppressive therapy, typically with mycophenolate mofetil or cyclophosphamide and with glucocorticoids, although these treatments are not uniformly effective. Within 10 years of an initial SLE diagnosis, 5 to 20% of patients with LN develop end-stage kidney disease.   

BLyS, a B-cell survival factor, is overexpressed in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases.  Belimumab is an inhibitor that targets B-lymphocyte stimulator (BLyS) protein, which may reduce the number of abnormal B cells by blocking the binding of BLyS to its receptors on B-cells. An intravenous (IV) formulation of belimumab was approved by the FDA in 2011.

A subcutaneous formulation of the medication was approved by the FDA in July 2017. 

Benlysta® (belimumab) is indicated for the treatment of:

  • Patients aged 5 years and older with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy
  • Patients aged 5 years and older with active lupus nephritis who are receiving standard therapy.
  • Limitations of Use: The efficacy of Benlysta has not been evaluated in patients with severe active central nervous system lupus. Benlysta has not been studied in combination with other biologics. Use of Benlysta is not recommended in these situations.

Voclosporin is a calcineurin-inhibitor immunosuppressant. Activation of lymphocytes involve an increase in intracellular calcium concentrations that bind to the calcineurin regulatory site and activate calmodulin binding catalytic subunit and through dephosphorylation, activates the transcription factor Nuclear Factor of Activated T-Cell Cytoplasmic (NFATc). The immunosuppressant activity results in inhibition of lymphocyte proliferation, T-cell cytokine production, and expression of T-cell activation surface antigens.

Lupkynis™ (voclosporin) is indicated in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis

The intent of this policy is to communicate the medical necessity criteria for belimumab (Benlysta®) and voclosporin (Lupkynis™) as provided under the member's prescription drug benefit.

Systemic Lupus Erythematosus 
INITIAL CRITERIA Belimumab (Benlysta®) is approved when ALL of the following are met:

  1. Diagnosis of active systemic lupus erythematosus; and
  2. Autoantibody positive (ie, anti-nuclear antibody [ANA] titer greater than or equal to 1:80 or anti-dsDNA level greater than or equal to 30 IU/mL), antibodies to DNA [Anti-dsDNA], Anti-Smith [Anti-Sm]); and
  3. Currently receiving at least one standard of care treatment for active systemic lupus erythematosus (eg, antimalarials [eg, hydroxychloroquine], corticosteroids, NSAIDs, or immunosuppressants); and
  4. Prescribed by or in consultation with a rheumatologist; and
  5. Member is 5 years of age or older

 
Initial Authorization duration: 6 months

REAUTHORIZATION CRITERIA: Belimumab (Benlysta®) is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years

Lupus Nephritis
INITIAL CRITERIA Belimumab (Benlysta®) is approved when ALL of the following are met:

  1. Member has active lupus nephritis confirmed by kidney biopsy; and
  2. Member is receiving standard therapy for lupus nephritis (e.g. corticosteroids, immunosuppressants, azathioprine); and
  3. Prescribed by or in consultation with a rheumatologist or nephrologist; and
  1. Member is 5 years of age or older


INITIAL CRITERIA Voclosporin (Lupkynis™) is approved when ALL of the following are met:

  1. Diagnosis of active lupus nephritis; and
  2. Member is 18 years of age or older; and
  3. Used in combination with mycophenolate mofetil and corticosteroids; and
  4. Prescribed by or in consultation with nephrologist or rheumatologist 

 
Initial Authorization duration: 6 months

REAUTHORIZATION CRITERIA: Belimumab (Benlysta®) or Voclosporin (Lupkynis™) is re-approved when there is documentation of positive clinical response to therapy.
 

Reauthorization duration: 2 years 


Lupkynis™ (Voclosporin)
Malignancies and serious infections: Increased risk for developing malignancies and serious infections with LUPKYNIS or other immunosuppressants that may lead to hospitalization or death.

Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE, Mohan C. Lupus nephritis. Nat Rev Dis Primers. 2020 Jan 23;6(1):7. doi: 10.1038/s41572-019-0141-9. PMID: 31974366. Accessed April 17, 2024.

Benlysta® [Package Insert]. Rockville, MD: Human Genome Sciences, Inc.; February 2023. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=2fa3c528-1777-4628-8a55-a69dae2381a3&type=display. Accessed April 17, 2024.

Gladman DD, Pisetski DS, Curtis MR. Clinical manifestations of systemic lupus erythematosus in adults. UpToDate. Waltham, MA: UpToDate Inc. https://www-uptodate-com.proxy1.lib.tju.edu/contents/overview-of-the-clinical-manifestations-of-systemic-lupus-erythematosus-in-adults?source=search_result&search=lupus&selectedTitle=1~150. Accessed on April 17, 2024.

Lupus facts and statistics. Lupus Foundation of America Web Site. https://resources.lupus.org/entry/facts-and-statistics. Published 2017. Accessed April 17, 2024.

Lupkynis™ (voclosporin) [prescribing information]. Rockville, MD: Aurinia Pharma U.S., Inc.; January 2021. Available from: https://d1io3yog0oux5.cloudfront.net/auriniapharma/files/pages/lupkynis-prescribing-information/FPI-0011+Approved+USPI++MG.pdf. Accessed April 17, 2024.


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Rx.01.33 Off-Label Use

Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit


Brand NameGeneric Name
Benlysta®belimumab
Lupkynis™voclosporin

NANA
386
  
7/1/2024Rx.01.262CommercialOyenusi, OluwadamilolaQ1-2024

Immunoglobulin A nephropathy (IgAN) or Berger's disease is a condition that damages the glomeruli inside the kidneys and can cause kidney disease. The kidney gets inflamed and can cause the kidneys to leak blood and protein which leads to loss of kidney function and kidney failure. 

Budesonide is a corticosteroid with potent glucocorticoid activity and weak mineralocorticoid activity that undergoes substantial first pass metabolism. Mucosal B-cells present in the ileum, including the Peyer's patches, express glucocorticoid receptors and are responsible for the production of galactose-deficient IgA1 antibodies (Gd-Ag1) causing IgA nephropathy. Through their anti-inflammatory and immunosuppressive effects at the glucocorticoid receptor, corticosteroids can modulate B-cell numbers and activity. It has not been established to what extent TARPEYO's efficacy is mediated via local effects in the ileum vs systemic effects.

TARPEYO is indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g.


The intent of this policy is to communicate the medical necessity criteria for Budesonide (Tarpeyo™) as provided under the member's prescription drug benefit. 

Budesonide (Tarpeyo™) is approved when ALL of the following are met:

  1. Diagnosis of primary immunoglobulin A nephropathy (IgAN) as confirmed by a kidney biopsy; and
  2. Member is 18 years of age or older; and
  3. Member is at risk of rapid disease progression (e.g., generally a urine protein-to-creatinine ratio (UPCR) greater than or equal to 1.5 g/g, or by other criteria such as clinical risk scoring using the International IgAN Prediction Tool); and
  4. Used to reduce proteinuria; and
  5. Estimated glomerular filtration rate (eGFR) greater than or equal to 35 ml/min/1.73 m2; and
  6. One of the following:
    1. Member has been on a minimum 90-day trial of maximally tolerated dose and will continue to receive therapy with one of the following:
      1. An angiotensin-converting enzyme (ACE) inhibitor (e.g., benazepril, lisinopril); or
      2. An angiotensin II receptor blocker (ARB) (e.g., losartan, valsartan); or
    2. Member is unable to tolerate BOTH ACE inhibitors and ARBs; and
  7. Inadequate response or inability to tolerate another glucocorticoid (e.g., prednisone, methylprednisolone); and
  8. Prescribed by or in consultation with a nephrologist

Authorization duration: 9 months


None

Tarpeyo (budesonide) [package insert]. Stockhelm, Sweden: Calliditas Therapeutics AB. December 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=938cada4-d6bf-4252-836f-dd40f9eadb4d. Accessed April 17, 2024. 

Cattran DC. IgA nephropathy: Treatment and prognosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 17, 2024. 


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​Rx.01.33 Off Label Use​
Brand NameGeneric Name
Tarpeyo™Budesonide

NANA
387
  
7/1/2024Rx.01.117CommercialOyenusi, OluwadamilolaQ1-2024

Cystic fibrosis (CF) is an inherited disease that affects mucus and sweat produced by secretory glands. The cystic fibrosis conductance regulator (CFTR) is a chloride channel present at the surface of epithelial cells in multiple organs. Mutations in this gene alter its ability to regulate the transport of chloride, sodium, and bicarbonate, leading to thick secretions in the lungs, pancreas, and other organs. Thickening of mucus can provide an environment for bacteria to grow, leading to repeated infections. Mucus blockage prevents pancreatic digestive enzymes from reaching the small intestine, reducing fat and protein absorption, which can lead to malnourishment. CF also causes sweat to become salty, which can lead to dehydration and fatigue when sweat leaves the body.

Approximately 30,000 people in the United States, and 70,000 worldwide, are living with cystic fibrosis (CF).  Over 2000 mutations in the CFTR gene have been identified.  The most common of which is the F508del mutation, affecting approximately 90% of those with CF.  Approximately 50% of those with CF are homozygous for F508Del mutation.  Other mutations in the CTFR gene include, but are not limited to: G551D, G1244E, G1349D, G178R, G551S, R117H, S1251N, S1255P, S549N and S549R,etc.

Ivacaftor (Kalydeco®)

Ivacaftor (Kalydeco®) is indicated for the treatment of CF in patients age 1 month and older who have one mutation in the CFTR gene that is responsive to ivacaftor based on clinical and/or in vitro assay data* as noted in the prescribing information.  

Ivacaftor is a potentiator of the CFTR protein, which promotes increased chloride transport by potentiating the gating (channel-open probability) of the CFTR protein, and improves the regulation of salt and water absorption and secretion in various tissues.

Lumacaftor/ivacaftor (Orkambi®)

Lumacaftor/ivacaftor (Orkambi®) is indicated for the treatment of CF in patients age 1 years and older who are homozygous for the F508del mutation in the CFTR gene*.

The F508del mutation causes protein misfolding resulting in impaired processing and gating of the CFTR protein. Lumacaftor improves the conformational stability of F508del-CFTR, resulting in increased processing and gating activity. Ivacaftor adds the benefit of potentiating gating of the CFTR protein.

*If genotype unknown, an FDA-cleared CF mutation test should be performed to detect the presence of the F508del mutation on both alleles of the CFTR gene.

Elexacaftor/tezacaftor/ivacaftor and ivacaftor (Trikafta™)

Elexacaftor/tezacaftor/ivacaftor and ivacaftor (Trikafta™) is indicated for the treatment of CF in patients aged 2 years and older who have at least one F508del mutation in the CFTR gene or a mutation in the CFTR gene that is responsive based on in vitro data.

Elexacaftor and tezacaftor bind to different sites on the CFTR protein and have an additive effect in facilitating the cellular processing and trafficking of F508del-CFTR to increase the amount of CFTR protein delivered to the cell surface compared to either molecule alone. Ivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface.

*If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one F508del mutation.

Tezacaftor/ivacaftor (Symdeko®)

Tezacaftor/ivacaftor (Symdeko®) is indicated for the treatment of CF in patients age 6 years and older who are homozygous for the F508del mutation or who have at least one mutation in the CFTR gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence*.

Tezacaftor facilitates the cellular processing and trafficking of normal and select mutant forms of CFTR (including F508del-CFTR) to increase the amount of mature CFTR protein delivered to the cell surface. Ivacaftor is a potentiator of the CFTR protein, which facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein at the cell surface

*If genotype unknown, an FDA-cleared CF mutation test should be performed to detect the presence of a CFTR mutation followed by verification with bi-directional sequencing.


The intent of this policy is to communicate the medical necessity criteria for ivacaftor (Kalydeco®), lumacaftor/ivacaftor (Orkambi®), elexacaftor/tezacaftor/ivacaftor and ivacaftor (Trikafta™), and tezacaftor/ivacaftor (Symdeko®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA:  Ivacaftor (Kalydeco®) is approved when ALL of the following are met:

  1. Diagnosis of cystic fibrosis (CF); and
  2. Member is 1 month of age or older; and
  3. Prescribed by or in consultation with a pulmonologist or specialist affiliated with a CF care center; and
  4. Presence of one mutation in the CFTR gene that is responsive to ivacaftor as noted in the Prescribing Information (if the patient's genotype is unknown, an FDA-cleared test must be used to detect the presence of CFTR mutation followed by verification with bi-directional sequencing when recommended by the mutation test)


INITIAL CRITERIA: Lumacaftor/ivacaftor (Orkambi®) is approved when ALL of the following are met:

  1. Diagnosis of cystic fibrosis (CF); and
  2. Member is 1 year of age or older; and
  3. Prescribed by or in consultation with a pulmonologist or specialist affiliated with a CF care center; and
  4. Homozygous for the F508del mutation in the CFTR gene (if the patient's genotype is unknown, an FDA-cleared CR mutation test must be performed to determine the presence of the F508del mutation on both alleles of the CFTR gene) 

 
INITIAL CRITERIA: Elexacaftor/tezacaftor/ivacaftor and ivacaftor (Trikafta™) is approved when ALL of the following are met:

  1. Diagnosis of cystic fibrosis (CF); and
  2. Member is 2 years of age or older; and
  3. One of the following:
    1. Member has at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene as detected by an FDA-cleared cystic fibrosis mutation test; OR
    2. Member has at least one mutation in the CFTR gene that is responsive based on in vitro data to elexacaftor/tezacaftor/ivacaftor (Trikafta™) as noted in the Prescribing Information; and
  1. Prescribed by or in consultation with a pulmonologist or specialist affiliated with a CF care center

 
INITIAL CRITERIA: Tezacaftor/ivacaftor (Symdeko®) is approved when ALL of the following are met: 

  1. Diagnosis of cystic fibrosis (CF); and
  2. Member is 6 years of age or older; and
  3. Prescribed by or in consultation with a pulmonologist or specialist affiliated with a CF care center; and
  4. Documentation of one of the following:
    1. Member is homozygous for the F508del mutation; or
    2. Member has at least one tezacaftor/ivacaftor responsive mutation in the CFTR gene as noted in the Prescribing Information (If the patient's genotype is unknown, an FDA-cleared test must be used to detect the presence of CFTR mutation followed by verification with bi-directional sequencing when recommended by the mutation test).

 

Initial Authorization duration: 2 years

REAUTHORIZATION CRITERIA: Ivacaftor (Kalydeco®), Lumacaftor/ivacaftor (Orkambi®), Elexacaftor/tezacaftor/ivacaftor and ivacaftor (Trikafta™), or Tezacaftor/ivacaftor (Symdeko®) is re-approved when there is positive clinical response to therapy (e.g., improvement in lung function or decreased number of pulmonary exacerbations).
Reauthorization duration: 2 years 


None

Accurso FJ, Rowe SM, Clancy JP, et al. Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med. 2010;363(21):1991-2003.

Aherns R, Rodriguez S, Yen K, Davies JC. VX-770 in subjects 6 to 11 years with cystic fibrosis and the G551D-CFTR mutation [abstract]. Pediatr Pulmonol. 2011;46(suppl 34):283.

Boyle MP, Bell S, Konstan MW, McColley SA, Wisseh S, Spencer-Green G. VX-809, an investigational CFTR corrector, in combination with VX-770, an investigational CFTR potentiator, in subjects with CF and homozygous for the F508del-CFTR mutation [abstract]. Pediatr Pulmonol. 2011;46(suppl 34):287.

Castellani C, Cuppens H, Macek M Jr, Cassiman JJ, Kerem E, Durie P, Tullis E,  Assael BM, Bombieri C, Brown A, Casals T, Claustres M, Cutting GR, Dequeker E, Dodge J, Doull I, Farrell P, Ferec C, Girodon E, Johannesson M, Kerem B, Knowles  M, Munck A, Pignatti PF, Radojkovic D, Rizzotti P, Schwarz M, Stuhrmann M, Tzetis M, Zielenski J, Elborn JS. Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. J Cyst Fibros. 2008 May;7(3):179-96. doi: 10.1016/j.jcf.2008.03.009.

Chen Y, Luo X, Dubey N, et al. Drug-drug interaction between VX-770 and CYP3A modulators [abstract]. J Clin Pharmacol. 2011;51:1348.

Drumm ML, Ziady AG, Davis PB. Genetic variation and clinical heterogeneity in cystic fibrosis. Annu Rev Pathol. 2012;7:267-282.

Flume PA, Borowitz D, Liou T, et al. VX-770 in subjects with CF and homozygous for the F508del-CFTR mutation [abstract]. Pediatr Pulmonol. 2011;46(suppl 34):284-285.

Kalydeco® (Ivacaftor) [package insert]. Boston, MA. Vertex Pharmaceuticals, Inc; December 2020. Available at: https://pi.vrtx.com/files/uspi_ivacaftor.pdf. Accessed on April 17, 2024.

Orkambi® (lumacaftor/ivacaftor) [package insert]. Boston, MA: Vertex Pharmaceuticals Incorporated; February 2023. Available at: https://pi.vrtx.com/files/uspi_lumacaftor_ivacaftor.pdf. Accessed on April 17, 2024.

McKone EF, Borowitz D, Drevinek P, et al. Long-term safety and efficacy of investigational CFTR potentiator, VX-770, in subjects with CF [abstract]. Pediatr Pulmonol. 2011;46(suppl 34):284.

Mogayzel PJ Jr, Naureckas ET, Robinson KA, Mueller G, Hadjiliadis D, Hoag JB, Lubsch L, Hazle L, Sabadosa K, Marshall B; Pulmonary Clinical Practice Guidelines Committee. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2013 Apr 1;187(7):680-9.

National Heart, Lung, and Blood Institute. Cystic Fibrosis. Bethesda, MD. Accessed April 17, 2024.

Ramsey BW, Davies J, McElvaney NG, et al; VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011; 365(18):1663-1672.

Robinson KA, Saldanha IJ, McKoy NA. Management of infants with cystic fibrosis: a summary of the evidence for the Cystic Fibrosis Foundation working group on care of infants with cystic fibrosis. J Pediatr. 2009;155(suppl 6): S94-S105.

Simon, RH. Cystic fibrosis: Overview of the treatment of lung disease. In: UpToDate. Waltham, MA. Accessed on April 17, 2024.

Symdeko® (tezacaftor/ivacaftor) [package insert]. Boston, MA. Vertex Pharmaceutical Inc.; June 2022. Available at: https://pi.vrtx.com/files/uspi_tezacaftor_ivacaftor.pdf. Accessed April 17, 2024.

Trikafta™ (elexacaftor/tezacaftor/ivacaftor and ivacaftor) [package insert]. Boston, MA: Vertex Pharmaceuticals Incorporated; October 2021. Available at: https://pi.vrtx.com/files/uspi_elexacaftor_tezacaftor_ivacaftor.pdf. Accessed on April 17, 2024.

Van Goor F, Hadida S, Grootenhuis PD, et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci U S A. 2009;106(44):18825-18830.

Van Goor F, Yu H, Burton B, Huang T, Hoffman B, Negulescu P. VX-770 potentiation of CFTR forms with channel gating defects in vitro [abstract]. Pediatr Pulmonol. 2011;46(suppl 34):215.

Woodworth BA, Zhang S, Skinner D, Sorscher EJ, Rowe SM. Comparison of CFTR and ciliary beat frequency activation by the CFTR modulators VX-770, VRT532, and UCCF-152 in primary sinonasal epithelial cultures [abstract]. Pediatr Pulmonol. 2011;46(suppl 34):251-252.

Yu H, Burton B, van Goor F. VX-770, an investigational CFTR potentiator, acts on multiple CFTR forms in vitro [abstract]. Pediatr Pulmonol. 2010;45(suppl 33):318-319

 


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Rx.01.33 Off-Label Use 
Drug Name Generic Name 
Kalydeco®Ivacaftor
Orkambi®Lumacaftor/ivacaftor
Trikafta™Elexacaftor/tezacaftor/ivacaftor and ivacaftor
Symdeko®Tezacaftor/ivacaftor

NANA
388
  
7/1/2024Rx.01.122CommercialOyenusi, OluwadamilolaQ1-2024

Multiple sclerosis (MS) is the most common autoimmune, inflammatory, demyelinating disease affecting the central nervous system (CNS).  An unknown stimulus causes the immune system to attack the myelin sheath that protects nerves, leading to symptoms such as weakness, numbness, vision loss, and gait disturbances. More than 2.3 million people are affected by MS worldwide.

Dalfampridine (Ampyra®) is indicated to improve walking in patients with MS.

Dalfampridine is a broad spectrum potassium channel blocker.  The mechanism by which dalfampridine exerts its therapeutic effect has not been fully elucidated.  In animal studies, dalfampridine has been shown to increase conduction of action potentials in demyelinated axons through inhibition of potassium channels.


The intent of this policy is to communicate the medical necessity criteria dalfampridine (Ampyra®) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA: Dalfampridine (Ampyra®) is approved when ALL the following are met:

  1. Diagnosis of multiple sclerosis; and
  2. Member is 18 years of age or older; and
  3. Member has difficulty walking; and
  4. Prescribed by or in consultation with a neurologist; and
  5. One of the following:
    1. Member has an expanded disability status scale (EDSS) score less than or equal to 7; or
    2. Member is not restricted to using a wheelchair (if EDSS is not measured)

 

Initial authorization duration: 6 months

CONTINUATION CRITERIA: Dalfampridine (Ampyra®) is re-approved when BOTH of the following are met:

  1. Documentation of a 20% improvement in walking speed; and
  2. Prescribed by or in consultation with a neurologist

 

Continuation authorization duration: 2 years


None

Ampyra® (dalfampridine) [package insert]. Ardsley, NY. Acorda Therapeutics, Inc. June 2022. Available from: https://ampyra.com/prescribing-information.pdf. Accessed April 17, 2024.

Olek, MJ. Mowry, E. Pathogenesis and epidemiology of multiple sclerosis. UpToDate. March 2023. Available at: https://www.uptodate.com/contents/pathogenesis-and-epidemiology-of-multiple-sclerosis. Accessed April 17, 2024.


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Rx.01.33 Off-Label Use 
Brand NameGeneric Name
AmpyraDalfampridine

NANA
390
  
7/1/2024Rx.01.155CommercialOyenusi, OluwadamilolaQ1-2024
Diclofenac epolamine 1.3% (Flector®/Licart® Patch) is indicated for the topical treatment of acu​te pain due to minor strains, sprains, and contusions in adults and pediatric patients 6 years or older.

Generic diclofenac epolamine patch is  indicated for the topical treat​ment of acute pain due to minor strains, sprains, and contusions in adults

Diclofenac sodium 1.5% and 2% solution (Pennsaid) is indicated for the treatment of the pain of osteoarthritis of the knee(s).

Diclofenac reversibly inhibit cyclooxygenase 1 and 2 (COX-1 and COX-2) enzymes, which results in decreased formation of prostaglandin precursors. Diclofenac also has antipyretic, analgesic, and anti-inflammatory properties.

The intent of this policy is to communicate the medical necessity criteria for diclofenac epolamine 1.3% (Flector®/Licart® Patch), diclofenac sodium 2% solution, and diclofenac sodium (Pennsaid®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: diclofenac epolamine (Flector®/Licart®) patch, diclofenac sodium 2% solution or Pennsaid® is approved when BOTH of the following are met:

  1. Diagnosis of pain; and
  2. ONE of the following:
    1. BOTH of the following:
      1. Inadequate response or inability to tolerate TWO of the following:
        1. Meloxicam
        2. Celecoxib
        3. Other oral NSAID; and
      2. Inadequate response or inability to tolerate ONE of the following:
        1. Generic topical diclofenac gel 1%
        2. Generic topical diclofenac solution 1.5%; or
  3. BOTH of the following:
    1. Member is 65 years of age or older; and
    2. Inadequate response or inability to tolerate ONE of the following:
      1. Generic topical diclofenac gel 1%
      2. Generic topical diclofenac solution 1.5%
Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: diclofenac epolamine (Flector®/Licart®) patch, diclofenac sodium 2% solution or Pennsaid® is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years

Diclofenac

Cardiovascular risk: Nonsteroidal anti-inflammatory drugs (NSAIDs) may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.

Diclofenac is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.

GI risk: NSAIDs cause an increased risk of serious GI adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These reactions can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious GI events.

Galer BS, Rowbotham M, Perander J, et al. Topical diclofenac patch relieves minor sports injury pain: results of a multicenter controlled clinical trial. J Pain Symptom Manage. 2000 Apr;19(4):287-94.

Flector patch (diclofenac epolamine patch) [product information].  New York, NY: Pfizer, Inc. April 2021. Available at: http://labeling.pfizer.com/ShowLabeling.aspx?id=829. Accessed April 17, 2024.

Licart™ (diclofenac epolamine) topical system [prescribing information]. Parsippany, NJ: IBSA Pharma Inc.: April 2021. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=851c8b39-6056-4bbc-812e-b9b13977c1ac. Accessed April 17, 2024.

Pennsaid (diclofenac sodium topical solution) Lake Forest, IL. Horizon Pharma USA Inc. [product information]. January 2022. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=802cd382-443d-48e3-9c9d-fd946c73c79f&type=display. Accessed April 17, 2024.

Diclofenac epolamine patch prescribing information. North Wales, PA. Teva Pharmaceuticals USA, Inc. December 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bda1c346-56ff-4197-9a19-7f0cc7f9ebad. Accessed April 17, 2024.



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Off-Label Use Rx.01.33

Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit Rx.01.76

Brand NameGeneric Name
Flector®/Licart® PatchDiclofenac epolamine 1.3% patch
Pennsaid® SolutionDiclofenac sodium 1.5%, 2% solution

Flector®/Licart® Patch, Pennsaid®diclofenac epolamine 1.3%, diclofenac sodium 1.5%, 2% solution
392
  
7/1/2024Rx.01.268CommercialOyenusi, OluwadamilolaQ1-2024
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that causes muscle weakness, disability, and eventually death, with a median survival of three to five years. The hallmark of ALS is the combination of upper motor neuron (UMN) and lower motor neuron (LMN) involvement. The LMN findings of weakness, atrophy, and fasciculations are a direct consequence of muscle denervation. The UMN findings of hyperreflexia and spasticity result from degeneration of the lateral corticospinal tracts in the spinal cord.

Edaravone is an oral suspension indicated for the treatment of amyotrophic lateral sclerosis (ALS).

Edaravone is neuroprotective agent working in the central nervous system. Edaravone is a free radical and peroxynitrite scavenger that prevents oxidative damage to the cell membranes and may contribute to inhibiting the progression of ALD. However, the mechanism of edaravone slowing the decline of physical function in patients with ALS is unknown. 

​The intent of this policy is to communicate the medical necessity criteria for Edaravone (Radicava ORS®) as provided under the member's prescription drug benefit. 




INITIAL CRITERIA: Edaravone (Radicava ORS®) is approved when ALL of the following are met:

  1. Diagnosis of "definite" or "probable" amyotrophic lateral sclerosis (ALS) per the revised EL Escorial and Airlie House diagnostic criteria; and
  2. Prescribed by or in consultation with a neurologist with expertise in the diagnosis of ALS; and
  3. Member has scores greater than or equal to 2 in all items of the ALS Functional Rating Scale-Revised (ALSFRS-R) criteria at the start of treatment; and 
  4. Member has a percent (%) forced vital capacity (%FVC) greater than or equal to 80% at the start of treatment; and
  5. Member is not dependent on invasive ventilation or tracheostomy 

 
Initial authorization duration: 12 months

REAUTHORIZATION CRITERIA: Edaravone (Radicava ORS®) is re-approved when BOTH of the following are met:

  1. Documentation of positive clinical response to therapy (e.g., slowing in the decline of functional abilities); and
  2. Member is not dependent on invasive ventilation of tracheostomy 

 
Reauthorization duration: 12 months 


N/A
Radicava ORS® (Edaravone) [package insert]. Jersey City, NJ: Mitsubishi Tanabe Pharma America, Inc. Novemeber 2022. Available from: https://www.radicava.com/pdfs/radicava-prescribing-information.pdf. Accessed April 17, 2024.

Goyal NA. Disease-modifying treatment of amyotrophic lateral sclerosis. UpToDate website. Last updated April 2024. Available at: www.uptodate.com. Accessed April 17, 2024.


33/14/20243/14/20257/1/2024 1:24 AMNo presence informationsrv_ppsgw_P
​​Rx.01.33 Off Label Use



Brand NameGeneric Name
Radicava ORS®Edaravone

Radicava ORS®Edaravone
393
  
7/1/2024Rx.01.142CommercialOyenusi, OluwadamilolaQ1-2024
Epinephrine pens are indicated for the emergency treatment of allergic reactions (type I), including anaphylaxis, which may result from allergic reactions to insect stings, biting insects, foods, drugs, sera, diagnostic testing substances and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis.

Epinephrine is a sympathomimetic catecholamine that is an agonist at alpha and beta adrenergic receptors.  Through its effects at the alpha adrenergic receptors, epinephrine cause vasoconstriction to counter vasodilation and increased vascular permeability that may occur during an anaphylactic reaction.

Currently available products include EpiPen®, Epi-Pen Jr®, Auvi-Q®, and epinephrine auto-injectors. 

The intent of this policy is to communicate the medical necessity criteria for Auvi-Q® , EpiPen®, and EpiPen Jr.® as provided under the member's prescription drug benefit.




Auvi Q®, EpiPen®, EpiPen Jr.® is approved when ALL of the following are met:

  1. ONE of the following:
    1. Documentation of a demonstrated inability to use one chemically equivalent generic agent; or 
    2. The member has a genuine allergic reaction to an inactive ingredient in generic agent(s) (allergic reaction(s) must be clearly documented in the patient's medical record); and
  2. For Auvi Q® only, documentation that the member or the member's caregivers would be unable to utilize the alternative epinephrine auto-injector devices (e.g., epinephrine) due to significant visual, physical, or functional impairment

Approval duration: 2 years 


N/A
Auvi-Q® (epinephrine injection) [package insert]. Richmond, VA. : Kaleo, Inc. August 2019.  Available at:  https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6180fb40-7fca-4602-b3da-ce62b8cd2470&type=display. Accessed April 17, 2024.

 

EpiPen®, EpiPen Jr® (epinephrine injection) [package insert]. Morgantown, WE: Mylan Specialty L.P.; February 2023. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?type=display&setid=7560c201-9246-487c-a13b-6295db04274a. Accessed April 17, 2024.

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Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Pharmacy Benefit
Rx.01.33 Off-Label Use

Brand NameGeneric Name
Auvi-Q®, EpiPen®, EpiPen Jr®Epinephrine

Auvi-Q®, EpiPen®, EpiPen Jr.® epinephrine
394
  
7/1/2024Rx.01.112CommercialOyenusi, OluwadamilolaQ1-2024
Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a condition that is characterized by a constant urge to move the legs due to uncomfortable sensations. The symptoms are usually worse during the night and are relieved temporarily by movement of the legs. The risk of RLS has been linked to other conditions such as anemia, kidney disease, multiple sclerosis, and diabetes. Treatment drug classes for RLS included dopaminergic agents, alpha-2-delta calcium channel ligands, among others.

Post herpetic neuralgia (PHN) is a complication of herpes zoster that is classified by severe pain in the areas where the rash was located, even after it has cleared. The pain usually will resolve within a few weeks or months but it can last for years in some cases, which lead to an interference with daily life.

Gabapentin is structurally related to the neurotransmitter gamma aminobutyric acid (GABA).  It has no effect on GABA binding, uptake, or degradation.  The exact mechanism by which gabapentin exerts its effect in restless leg syndrome (RLS) and postherpetic neuralgia (PHN) is unknown.  In vitro studies show that gabapentin binds with high affinity to the alpha-2-delta subunit of voltage activated calcium channels.  The relationship of this binding and gabapentin's therapeutic effect is not known.  Gabapentin enacarbil is a prodrug of gabapentin.

Gabapentin (Gralise®) is indicated for the management of postherpetic neuralgia (PHN).

Gabapentin enacarbil (Horizant®) is indicated for the treatment of moderate-to-severe primary RLS and PHN in adults.

Pregabalin is structurally related to the neurotransmitter gamma aminobutyric acid (GABA).  It has no effect on GABA binding, uptake, or degradation.  The exact mechanism by which pregabalin exerts its effects is unknown. Pregabalin binds with high affinity to the alpha-2-delta subunit of voltage activated calcium channels in central nervous system tissues. This binding may be involved in pregabalin's antinociceptive and antiseizure effects.

Pregabalin (Lyrica CR®) is indicated for the management of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia (PHN).

The intent of this policy is to communicate the medical necessity criteria for gabapentin (Gralise®/Horizant®) and pregabalin (Lyrica CR®) as provided under the member's prescription drug benefit.



Post-herpetic neuralgia
 
INITIAL CRITERIA: Gabapentin (Gralise®), gabapentin (Horizant®) or pregabalin (Lyrica CR®) is approved when all of the following are met:

  1. Diagnosis of post-herpetic neuralgia, and
  2. Member is 18 years of age or older; and
  3. Inadequate response or inability to tolerate ONE of the following:
    1. Gabapentin; or
    2. Pregabalin

Initial Authorization duration: 2 years

REAUTHORIZATION CRITERIA: Gabapentin (Gralise®), or gabapentin enacarbil (Horizant®), or Pregabalin (Lyrica CR®) is re-approved when there is positive clinical response to therapy.
Reauthorization duration: 2 years 
__________________________________________________________________________________________________

Restless legs syndrome
 
INITIAL CRITERIA: Gabapentin enacarbil (Horizant®) is approved ALL of the following are met:

  1. Diagnosis of moderate-to-severe primary restless legs syndrome; and
  2. Inadequate response or inability to tolerate BOTH of the following:
    1. Pramipexole; and
    2. Ropinirole; and
  3. Member is 18 years of age or older

Initial Authorization duration: 2 years
 

REAUTHORIZATION CRITERIA Gabapentin enacarbil (Horizant®) is re-approved when there is positive clinical response to therapy.
Reauthorization duration: 2 years 
___________________________________________________________________________________________________

Diabetic peripheral neuropathy
INITIAL CRITERIA: Pregabalin (Lyrica CR®) is approved when ALL of the following are met:

  1. Diagnosis of neuropathic pain associated with diabetic peripheral neuropathy; and
  2. Inadequate response or inability to tolerate ONE of the following:
    1. Gabapentin; or
    2. Pregabalin; and
  3. Member is 18 years of age or older

Initial Authorization duration: 2 years

 
REAUTHORIZATION CRITERIA Pregabalin (Lyrica CR®) is re-approved when there is positive clinical response to therapy.
Reauthorization duration: 2 years


N/A
Gabapentin. Available at: http://www.micromedexsolutions.com. Accessed April 17, 2024.

Gralise® (gabapentin) [package insert]. Newark, CA. Depomed, Inc. April 2023. Available at: https://www.gralise.com/static/Gralise_full_Prescribing_Information_-_Printed-b9a705a9011191f3f63f0a16e352cf4d.pdf . Accessed April 17, 2024. 

Dopp JM, Phillips BG. Sleep–Wake Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGra`w-Hill; .http://accesspharmacy.mhmedical.com.libproxy.temple.edu/content.aspx?bookid=1861&sectionid=134128126. Accessed April 17, 2024.

Horizant® (gabapentin enacarbil) [package insert].Santa Clara, CA. Xenoport, Inc. August 2022. Available at: https://www.horizant.com/pdf/Horizant_PrescribingInformation.pdf . Accessed April 17, 2024.

Pregabalin. Available at: http://www.micromedexsolutions.com. Accessed April 17, 2024.

Lyrica CR® (pregabalin hydrochloride) [package insert]. New York, NY. Pfizer. December 2023. Available from https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209501s000lbl.pdf. Accessed April 17, 2024.

Shingles (Herpes Zoster). Centers for Disease Control and Prevention. https://www.cdc.gov/shingles/about/complications.html. Published January 19, 2019. Accessed April 17, 2024.

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Off Label Use Rx.01.33
Brand NameGeneric Name
Gralise®gabapentin
Horizant®Gabapentin enacarbil
Lyrica CR®pregabalin controlled-release

Gralise®/Horizant®, Lyrica CR®gabapentin, pregabalin
395
  
7/1/2024Rx.01.269CommercialOyenusi, OluwadamilolaQ1-2024
Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare, genetic, developmental epileptic encephalopathy characterized by early onset, treatment refractory seizures, motor impairments, and severe neurodevelopmental delays. CDD is estimated to affect 1 in 40,000 to 1 in 60,000 live births, with reported cases increasing as genetic testing becomes more common. The clinical severity of CDD is variable, and patients may experience one or more of several different seizure types, including infantile spasms (IS) and tonic-clonic, atonic, clonic, myoclonic, absence, and focal seizures. Patients with CDD generally respond poorly to currently approved drugs for varying seizure types, and there are currently no other approved treatments specifically for CDD.

The mechanism by which Ztalmy exerts its therapeutic effects in the treatment of seizures associated with CDD is unknown, but its anticonvulsant effects are thought to result from positive allosteric modulation in both the synaptic and extra synaptic gamma-aminobutyric acid-A (GABAA) receptors in the central nervous system (CNS), decreasing neuron excitability.

Ztalmy is indicated for the treatment of seizures associated with CDD in patients ≥ 2 years of age. 

​The intent of this policy is to communicate the medical necessity criteria for Ganaxolone (Ztalmy®) as provided under the member's prescription drug benefit. 




INITIAL CRITERIA Ganaxolone (Ztalmy®) is approved when ALL of the following are met: 

  1. Diagnosis of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD); and 
  2. Documentation of mutation in the CDKL5 gene; and 
  3. Member is experiencing motor seizures (e.g., bilateral tonic, generalized tonic-clonic, bilateral clonic, atonic, focal, or bilateral tonic-clonic); and 
  4. One of the following: 
    1. Inadequate response or inability to tolerate two formulary anticonvulsants (e.g., valproic acid, levetiracetam, lamotrigine); or 
    2. Continuation of therapy with requested medication; and 
  5. Member is 2 years of age or older; and 
  6. Prescribed by or in consultation with a neurologist 

Initial authorization duration: 6 months 

REAUTHORIZATION CRITERIA Ganaxolone (Ztalmy®) is re-approved when BOTH of the following are met: 

  1. Documentation of positive clinical response to therapy (e.g., reduction in frequency of major motor seizures compared to baseline); and 
  2. Prescribed by or in consultation with a neurologist 

Reauthorization duration: 2 years


N/A
Amin S, Monaghan M, Aledo-Serrano A, et al. International Consensus recommendations for the assessment and management of individuals with CDKL5 deficiency disorder. Front Neurol. 2022;13:874695.

Food and Drug Administration (FDA). FDA approves drug for treatment of seizures associated with rare disease in patients two years of age and older [news release]. March 18, 2022. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-treatment-seizures-associated-rare-disease-patients-two-years-age-and-older. Accessed April 17, 2024.

Food and Drug Administration. Ztalmy (ganaxolone) summary review. March 18, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/215904Orig1s000SumR.pdf. Accessed April 17, 2024.

Jakimiec M, Paprocka J, Śmigiel R. CDKL5 deficiency disorder-a complex epileptic encephalopathy. Brain Sci. 2020;10(2):107.

Knight EMP, Amin S, Bahi-Buisson N, et al; Marigold Trial Group. Safety and efficacy of ganaxolone in patients with CDKL5 deficiency disorder: results from the double-blind phase of a randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2022;21(5):417-427.

Leonard H, Downs J, Benke TA, et al. CDKL5 deficiency disorder: clinical features, diagnosis, and management. Lancet Neurol. 2022;21(6):563-576.

Ztalmy (ganaxolone) [package insert]. Radnor, PA: Marinus Pharmaceuticals, Inc.; June 2023. Available from: https://marinuspharma.com/wp-content/uploads/2022/03/prescribing-information.pdf. Accessed April 17, 2024.
 


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​Rx.01.33 Off Label Use​
Brand NameGeneric Name
Ztalmy®Ganaxolone

Ztalmy®Ganaxolone
396
  
7/1/2024Rx.01.214CommercialOyenusi, OluwadamilolaQ1-2024
Hyperhidrosis, defined as the secretion of sweat in amounts greater than physiologically necessary to main thermoregulation, can adversely affect an individual's social and emotional well-being and overall daily function. It commonly involves the axillae, palms, and soles, but may also affect the face, groin, or any area of the body. Prescription antiperspirants such as aluminum chloride hexahydrate 20% (Drysol®) and topical glycopyrronium (Qbrexza™) are first line options for the treatment of hyperhidrosis. Second line treatment options include onabotulinumtoxin A injections and microwave thermolysis.

Glycopyrronium (Qbrexza™) is a competitive inhibitor of acetylcholine receptors that are located on certain peripheral tissues, including sweat glands. In hyperhidrosis, glycopyrronium inhibits the action of acetylcholine on sweat glands, reducing sweating.

Glycopyrronium (Qbrexza™) is indicated for the topical treatment of primary axillary hyperhidrosis in adults and pediatric patients 9 years of age and older.

​The intent of this policy is to communicate the medical necessity criteria for glycopyrronium (QbrexzaTM) as provided under the member's prescription drug benefit.




INITIAL CRITERIA:  Qbrexza™ (glycopyrronium) is approved when ALL of the following are met:

  1. Diagnosis of primary axillary hyperhidrosis for at least 6 months; and
  2. Member is 9 years of age or greater; and
  3. Prescribed by or in consultation with a dermatologist; and
  4. Hyperhidrosis Disease Severity Scale grade 3 or 4; and
  5. Documentation of an inadequate response or inability to tolerate aluminum chloride (e.g. Drysol)

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: Qbrexza™ (glycopyrronium) is re-approved when there is positive clinical response to therapy.

Reauthorization duration: 2 years


N/A
Qbrexza™ (glycopyrronium) [prescribing information]. Menlo Park, CA. Dermira., Inc. November 2022. Available at: https://getqbrexza.com/wp-content/themes/qbrexzadtp/assets/pdf/qbrexza-pi.pdf. Accessed April 17, 2024.

Smith CC, Pariser D. Primary focal hyperhidrosis. UpToDate Web site. Updated December 2022. www.uptodate.com. Accessed April 17, 2024.

Wade R, Rice S, Llewellyn A, et al. Interventions for hyperhidrosis in secondary care: a systematic review and value-of-information analysis. Health Technol Assess. 2017;21(80):1-280.  ​

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Off-Label Use Rx.01.33
Brand NameGeneric Name
Qbrexza™Glycopyrronium

Qbrexza™Glycopyrronium Topical
398
  
7/1/2024Rx.01.164CommercialOyenusi, OluwadamilolaQ1-2024
Interstitial lung diseases (ILDs) are a heterogenous group of disorders that are characterized by the inflammation and scarring of the lungs. Some ILDs have known causes and some are idiopathic. The treatment choices and prognosis vary among the different causes and types of ILDs.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, incurable fibrotic disorder of the lower respiratory tract that typically affects adults over the age of 40.  IPF is characterized by varying degrees of fibrosis, collagen deposits, and distortion of the pulmonary architecture. Although the specific initiating factor(s) leading to IPF are unknown, lung injury progresses due to the interaction of growth factors, cytokines, and other mediators, leading to fibroblast proliferation and excessive extracellular matrix deposition in the lungs.  Pharmacologic treatments are limited. Prior to the FDA approval of pirfenidone (Esbriet®) and nintedanib (Ofev®) in October 2014, no medications were approved for the treatment of IPF. Traditional approaches have included various anti-inflammatory and immunosuppressive agents; however, these approaches do not seem to be effective and are no longer considered part of routine maintenance care. Early trials of agents with antifibrotic properties were disappointing. Thus, treatment has predominantly been limited to supportive care, including oxygen therapy and pulmonary rehabilitation. Lung transplantation is also an option for selected patients. Five-year survival is approximately 20-30%

Systemic Sclerosis is a rare and heterogenous autoimmune disease characterized by immune dysregulation, microvascular damage, and organ fibrosis. Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis that tends to occur early in the course of disease.

Nintedanib (Ofev®) inhibits multiple receptor tyrosine kinases and nonreceptor tyrosine kinases, including platelet-derived growth factor (PDGFR alpha and PDGFR beta), fibroblast growth factor receptor (FGFR1, FGFR2, FGFR3), vascular endothelial growth factor (VEGFR1, VEGFR2, and VEGFR3), and Fms-like tyrosine kinase-3 (FLT3). Nintedanib binds competitively to the adenosine triphosphate (ATP) binding pocket of these receptors and blocks the intracellular signaling which is crucial for the proliferation, migration, and transformation of fibroblasts. Nintedanib (Ofev®) is indicated for the treatment of idiopathic pulmonary fibrosis and systemic sclerosis associated with Interstitial Lung Disease (SSc-ILD).

The precise mechanisms of action for pirfenidone (Esbriet®) have not been fully elucidated; however, pirfenidone may exert antifibrotic properties by decreasing fibroblast proliferation and the production of fibrosis-associated proteins and cytokines; may decrease the formation and accumulation of extracellular matrix (i.e., collagen) in response to transforming growth factor beta and platelet-derived growth factor. Pirfenidone is also believed to exert anti-inflammatory properties by decreasing the accumulation of inflammatory cells resulting from a variety of stimuli.  Pirfenidone (Esbriet®) is indicated for the treatment of idiopathic pulmonary fibrosis.

Nintedanib and pirfenidone appear to slow disease progression.  Neither medication is a cure for IPF.

The intent of this policy is to communicate the medical necessity criteria for pirfenidone (Esbriet®) and nintedanib (Ofev®) as provided under the member's prescription drug benefit.

Idiopathic Pulmonary Fibrosis (IPF)

INITIAL CRITERIA: Pirfenidone (Esbriet®) or Nintedanib (Ofev®) is approved when ALL of the following are met:

  1. Diagnosis of Idiopathic Pulmonary Fibrosis (IPF); and
  2. Member is 18 years of age or older; and
  3. Diagnosis was confirmed by BOTH of the following:
    1. High resolution CT scan or biopsy; and
    2. Member does not have evidence or suspicion of an alternative interstitial lung disease diagnosis; and
  4. Prescribed by or in consultation with a pulmonologist or lung transplant specialist

Initial authorization duration: 12 months

REAUTHORIZATION CRITERIA: Pirfenidone (Esbriet®) or Nintedanib (Ofev®) is re-approved when there is documentation of positive clinical response to therapy (e.g., member has experienced stabilization from baseline or a less than 10% decline in forced vital capacity (FVC))

Reauthorization duration: 12 months

 
Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD)
INITIAL CRITERIA: Nintedanib (Ofev®) is approved when ALL of the following are met:

  1. Diagnosis of Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD); and
  2. Member is 18 years of age or older; and
  3. Diagnosis was confirmed by BOTH of the following:
    1. High resolution CT scan or biopsy; and
    2. Member does not have evidence or suspicion of an alternative interstitial lung disease diagnosis; and
  4. Prescribed by or in consultation with a pulmonologist or lung transplant specialist

Initial authorization duration: 12 months

REAUTHORIZATION CRITERIA: Nintedanib (Ofev®) is re-approved when there is documentation of positive clinical response to therapy (e.g., member has experienced stabilization from baseline or a less than 10% decline in forced vital capacity (FVC))

Reauthorization duration: 12 months

 
Chronic Fibrosing Interstitial Lung Disease (ILDs) with a progressive phenotype
INITIAL CRITERIA: Nintedanib (Ofev®) is approved when ALL of the following are met:

  1. Diagnosis of Chronic Fibrosing Interstitial Lung Disease (ILDs) with a progressive phenotype; and
  2. Member is 18 years of age or older; and
  3. Disease has a progressive phenotype as observed by one of the following:
    1. Decline of forced vital capacity (FVC); or
    2. Worsening of respiratory symptoms; or
    3. Increased extent of fibrosis seen on imaging; and
  4. Diagnosis was confirmed by BOTH of the following:
    1. High resolution CT scan or biopsy; and
    2. Member does not have evidence or suspicion of an alternative interstitial lung disease diagnosis; and
  5. Prescribed by or in consultation with a pulmonologist or lung transplant specialist

Initial authorization duration: 12 months

REAUTHORIZATION CRITERIA: Nintedanib (Ofev®) is re-approved when there is documentation of positive clinical response to therapy (e.g. member has experienced stabilization from baseline or a less than 10% decline in forced vital capacity (FVC))

Reauthorization duration: 12 months


N/A
Esbriet® (pirfenidone) [prescribing information]. South San Francisco, CA. Genentech, Inc. February 2023. Available at: https://www.gene.com/download/pdf/esbriet_prescribing.pdf . Accessed April 17, 2024.

King TE. Treatment of idiopathic pulmonary fibrosis. UpToDate. February 2024. Available at: https://www.uptodate.com/contents/treatment-of-idiopathic-pulmonary-fibrosis?source=see_link&sectionName=MEDICAL%20THERAPIES&anchor=H13191574#H13191574. Accessed April 17, 2024

Ofev® (nintedanib) [prescribing information]. Ridgefield, CT. Boehringer Ingelheim. October 2022. Available at: https://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Ofev/ofev.pdf . Accessed April 17, 2024

Raghu G, et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis: An Update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med. 2015 Jul;192:e3-e19. DOI: 10.1164/rccm.201506-1063ST

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Off-Label Use Rx.01.33
Brand nameGeneric name
Ofev®nintedanib
Esbriet®pirfenidone

Esbriet®, Ofev®pirfenidone, nintedanib
400
  
7/1/2024Rx.01.248CommercialOyenusi, OluwadamilolaQ1-2024
​Cystic fibrosis is a progressive genetic condition that affects many areas of the body, including the lungs, digestive system, sweat glands and the reproductive system. Cystic fibrosis is caused by mutations in the CTFR gene, resulting in the abnormal transport of chloride and sodium ions across cell epithelia. In the respiratory system, this means there is less transport of water into the airway secretions, resulting in thick and viscous mucus accumulating in airways. These viscous secretions can obstruct the airways and promote respiratory infections, which can cause tissue damage. Common symptoms associated with cystic fibrosis include difficulty breathing, persistent productive cough and recurrent respiratory infections. Over time, these symptoms can worsen, resulting in worsening respiratory function and eventually even respiratory failure.

The precise mechanism of action of Bronchitol® in improving pulmonary function in cystic fibrosis patients is unknown.

Bronchitol® is indicated as add-on maintenance therapy to improve pulmonary function in adult patients 18 years and older with Cystic Fibrosis. Use Bronchitol® only for adults who have passed the Bronchitol® Tolerance Test.

The intent of this policy is to communicate the medical necessity criteria for Mannitol (Bronchitol®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Mannitol (Bronchitol®) is approved when all of the following are met:

  1. Diagnosis of cystic fibrosis; and
  2. Member is 18 years of age or older; and
  3. Member has passed the Bronchitol Tolerance Test (BTT); and
  4. Member has inadequate response or inability to tolerate ONE of the following:
    1. Inhaled hypertonic saline; or
    2. Pulmozyme (dornase alfa); and
  5. Prescribed by or in consultation with one of the following:
    1. Pulmonologist; or
    2. Specialist associated with a cystic fibrosis care center

Initial authorization duration: 2 years 


REAUTHORIZATION CRITERIA: Mannitol (Bronchitol®) is re-approved when there is documentation of positive clinical response to therapy (e.g. improvement in lung function [forced expiratory volume in one second {FEV1}])
Reauthorization duration: 2 years 


N/A
Bronchitol® (mannitol) [Package insert]. Cary, NC: Chiesi USA, Inc. October 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=454f092e-dcd0-47bd-a521-b07400403dad. Accessed April 17, 2024.

Katikin JP. Cystic fibrosis: genetics and pathogenesis. UpToDate. March 2024. Available at: https://www.uptodate.com/contents/cystic-fibrosis-genetics-and-pathogenesis. Accessed April 17, 2024

Katikin JP. Cystic fibrosis: clinical manifestations of pulmonary disease. UpToDate. February 2023. Available at: https://www.uptodate.com/contents/cystic-fibrosis-clinical-manifestations-of-pulmonary-disease. Accessed April 17, 2024



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Rx.01.33 Off Label Use​
​Brand Name​Generic Name
​Bronchitol®​Mannitol

Bronchitol®Mannitol
401
  
7/1/2024Rx.01.251CommercialOyenusi, OluwadamilolaQ1-2024
Migraine is a common primary headache disorder of unclear etiology. It is recurrent in nature and classically presents as moderate-to-severe head pain lasting 4-72 hours. Calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) may play important roles in mediating migraine attacks.

Rizatriptan binds with high affinity to human cloned 5-HT1B and 5-HT1D receptors. Rizatriptan has weak affinity for other 5-HT1 receptor subtypes (5-HT1A, 5-HT1E, 5-HT1F) and the 5-HT7 receptor, but has no significant activity at 5-HT2, 5-HT3, alpha- and beta-adrenergic, dopaminergic, histaminergic, muscarinic or benzodiazepine receptors. The therapeutic activity of rizatriptan in migraine can most likely be attributed to agonist effects at 5-HT1B/1D receptors on the extracerebral, intracranial blood vessels that become dilated during a migraine attack and on nerve terminals in the trigeminal system. Activation of these receptors results in cranial vessel constriction, inhibition of neuropeptide release and reduced transmission in trigeminal pain pathways.

MAXALT® and MAXALT-MLT® are indicated for the acute treatment of migraine with or without aura in adults and in pediatric patients 6 to 17 years old.

Naratriptan binds with high affinity to human cloned 5-HT1B/1D receptors. The therapeutic activity of AMERGE for the treatment of migraine headache is thought to be due to the agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels (including the arterio-venous anastomoses) and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

AMERGE is indicated for the acute treatment of migraine with or without aura in adults.

Frovatriptan binds with high affinity to 5-HT1B/1D receptors. The therapeutic activity of FROVA is thought to be due to the agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels (including the arterio-venous anastomoses) and sensory nerves of the trigeminal system which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

FROVA is indicated for the acute treatment of migraine with or without aura in adults.

Sumatriptan binds with high affinity to human cloned 5-HT1B/1D receptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine and cluster headaches through agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

IMITREX injection is indicated in adults for (1) the acute treatment of migraine, with or without aura, and (2) the acute treatment of cluster headache.

TOSYMRA is indicated for the acute treatment of migraine with or without aura in adults.

ONZETRA® Xsail® is indicated for the acute treatment of migraine with or without aura in adults.

ZEMBRACE SymTouch is indicated for the acute treatment of migraine with or without aura in adults.

Eletriptan binds with high affinity to 5-HT1B, 5-HT1D and 5-HT1F receptors, has modest affinity for 5-HT1A, 5-HT1E, 5-HT2B and 5-HT7 receptors. The therapeutic activity of RELPAX for the treatment of migraine headache is thought to be due to the agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels (including the arterio-venous anastomoses) and sensory nerves of the trigeminal system which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

RELPAX is indicated for the acute treatment of migraine with or without aura in adults.

Zolmitriptan binds with high affinity to human recombinant 5-HT1D and 5‑HT1B receptors, and moderate affinity for 5-HT1A receptors. The N-desmethyl metabolite also has high affinity for 5‑HT1B/1D and moderate affinity for 5‑HT1A receptors.

ZOMIG is indicated for the acute treatment of migraine with or without aura in adults.

ZOMIG Nasal Spray is indicated for the acute treatment of migraine with or without aura in adults and pediatric patients 12 years of age and older.

TREXIMET contains sumatriptan and naproxen. Sumatriptan binds with high affinity to cloned 5-HT1B/1D receptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine headache through agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of neuropeptide release. TREXIMET has analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action of TREXIMET, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).

TREXIMET is indicated for the acute treatment of migraine with or without aura in adults and pediatric patients 12 years of age and older.

Dihydroergotamine binds with high affinity to 5-HT1Dα and 5-HT1Dβ receptors. It also binds with high affinity to serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors, noradrenaline α2A, α2B and α1 receptors, and dopamine D2L and D3 receptors. The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effect at 5-HT1D receptors.

D.H.E. 45 (dihydroergotamine mesylate) Injection, USP is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes.

MIGRANAL® and TRUDHESA™ (dihydroergotamine mesylate) Nasal Spray is indicated for the acute treatment of migraine headaches with or without aura.

Rimegepant is a calcitonin gene-related peptide receptor antagonist.

NURTEC ODT is indicated for the acute treatment of migraine with or without aura in adults and for the preventive treatment of episodic migraine in adults.

Ubrogepant is a calcitonin gene-related peptide receptor antagonist.

UBRELVY is indicated for the acute treatment of migraine with or without aura in adults.

Lasmiditan binds with high affinity to the 5-HT1F receptor. Lasmiditan presumably exerts its therapeutic effects in the treatment of migraine through agonist effects at the 5-HT1F receptor; however, the precise mechanism is unknown.

REYVOW® is indicated for the acute treatment of migraine with or without aura in adults.

Erenumab-aooe is a human monoclonal antibody that binds to the calcitonin gene-related peptide (CGRP) receptor and antagonizes CGRP receptor function.

AIMOVIG is indicated for the preventive treatment of migraine in adults.

Fremanezumab-vfrm is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor.

AJOVY is indicated for the preventive treatment of migraine in adults.

Cluster headache is an uncommon primary headache disorder characterized by attacks of severe unilateral pain with ipsilateral autonomic symptoms. Pathophysiology is unclear; proposed mechanisms involve interaction of trigeminal nerve (TN) and trigeminovascular system, parasympathetic nerve fibers (trigeminal autonomic reflex), and hypothalamus.

Galcanezumab-gnlm is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor.

EMGALITY is indicated for the preventive treatment of migraine in adults and for the treatment of episodic cluster headache in adults.

Atogepant is a calcitonin gene-related peptide (CGRP) receptor antagonist.

QULIPTA is indicated for the preventive treatment of migraine in adults.

Zavegepant is a calcitonin gene-related peptide receptor antagonist.

Zavzpret™ is indicated for the acute treatment of migraine with or without aura in adults. 

The intent of this policy is to communicate the medical necessity criteria for rizatriptan (Maxalt®/Maxalt® MLT), naratriptan (Amerge®), frovatriptan (Frova®), sumatriptan (Imitrex®, Tosymra®, Onzetra® Xsail, Zembrace® Symtouch), eletriptan (Relpax®), zolmitriptan (Zomig®/ Zomig® ZMT), sumatriptan/naproxen (Treximet®), dihydroergotamine mesylate (D.H.E. 45®, Migranal®, Trudhesa™), Rimegepant (Nurtec™ ODT), ubrogepant (Ubrelvy™), lasmiditan (Reyvow®), erenumab (Aimovig™), fremanezumab (Ajovy™), galcanezumab (Emgality™), atogepant (Qulipta™), zavegepant (Zavzpret™) as provided under the member's prescription drug benefit. 

Acute Treatment of Migraine
 
INITIAL CRITERIA: Frova®, Imitrex®, Tosymra®, Relpax®, Onzetra® Xsail, Zembrace® Symtouch, zolmitriptan nasal spray, or Zomig®/zolmitriptan Zomig® ZMT is approved when ALL of the following are met:

  1. Diagnosis of migraine headache; and
  2. Use in the age group shown in the table below; and
  3. Inadequate response or inability to tolerate two generic triptans (e.g., eletriptan, naratriptan, rizatriptan, zolmitriptan, sumatriptan) as appropriate for the member's age
DrugAge Recommendation
RizatriptanAge 6 and up
Zolmitriptan (Zomig®/Zomig® ZMT)Age 12 and up
Eletriptan (Relpax®)Age 18 and up
NaratriptanAge 18 and up

Sumatriptan (Imitrex®, Onzetra® Xsail,

Zembrace® Symtouch, Tosymra®)

Age 18 and up
Frovatriptan (Frova®)Age 18 and up

 

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: Frova®, Imitrex®, Tosymra®, Relpax®, Onzetra® Xsail, Zembrace® Symtouch, zolmitriptan nasal spray or Zomig®/Zomig® ZMT is re-approved when there is documentation of positive clinical response to therapy.
 

Reauthorization duration: 2 years

INITIAL CRITERIA: Sumatriptan/naproxen (Treximet®) is approved when ALL of the following are met:

  1. Diagnosis of migraine headache; and
  2. Member is 12 years of age or older; and
  3. Inadequate response or inability to tolerate three generic triptans (e.g., eletriptan, naratriptan, rizatriptan, zolmitriptan, sumatriptan); and
  4. Inadequate response to concurrent administration of sumatriptan and naproxen as separate products


Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: Sumatriptan/naproxen (Treximet®) is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years

INITIAL CRITERIA: Dihydroergotamine mesylate (D.H.E. 45®) injection is approved when ALL of the following are met:

  1. Prescribed by or in consultation with one of the following specialists:
    1. Neurologist; or
    2. Pain specialist; or
    3. Headache specialist certified by the United Council of Neurologic Subspecialties; and
  2. Diagnosis of acute treatment of migraine or cluster headaches; and
  3. Member is 18 years of age or older; and
  4. Member has been instructed on proper preparation, injection, and disposal of medication; and
  5. ONE of the following:
    1. Inadequate response or inability to tolerate two, oral or nasal, triptans; or
    2. Triptan overuse, defined as using triptans greater than 8 days per month; and
  6. For brand D.H.E. 45 only, inadequate response or inability to tolerate generic dihydroergotamine injection or it is not available; and
  7. If member has 4 or more headache days per month, member must be currently treated with one of the following, unless there is a contraindication or intolerance to these medications:
    1. An antidepressant (i.e., Elavil [amitriptyline] or Effexor [venlafaxine])
    2. An anticonvulsant (i.e., Depakote/Depakote ER [divalproex sodium] or Topamax [topiramate])
    3. A beta-blocker (i.e., atenolol, propranolol, nadolol, timolol, or metoprolol)
    4. Atacand (candesartan)

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: Dihydroergotamine mesylate (D.H.E 45®) injection is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years

INITIAL CRITERIA: Dihydroergotamine mesylate (Migranal®) or dihydroergotamine mesylate HFA (Trudhesa™) is approved when ALL of the following are met:

  1. Diagnosis of moderate to severe migraine headache with or without aura; and
  2. Inadequate response or inability to tolerate TWO, oral or nasal, triptans; and
  3. If member has 4 or more headache days per month, member must be currently treated with one of the following, unless there is a contraindication or intolerance to these medications:
    1. An antidepressant (i.e., Elavil [amitriptyline] or Effexor [venlafaxine])
    2. An anticonvulsant (i.e., Depakote/Depakote ER [divalproex sodium] or Topamax [topiramate])
    3. A beta-blocker (i.e., atenolol, propranolol, nadolol, timolol, or metoprolol)
    4. Atacand (candesartan); and
  4. Prescribed by or in consultation with one of the following specialists:
    1. Neurologist; or
    2. Pain specialist; or
    3. Headache specialist certified by the United Council of Neurologic Subspecialities

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: Dihydroergotamine mesylate (Migranal®) or dihydroergotamine mesylate HFA (Trudhesa™) is re-approved when there is documentation of positive clinical response to therapy.
Reauthorization duration: 2 years

INITIAL CRITERIA: Rimegepant (Nurtec™ ODT), ubrogepant (Ubrelvy™), zavegepant (Zavzpret) or lasmiditan (Reyvow®) is approved when all of the following are met:

  1. Diagnosis of migraine with or without aura; and
  2. Will be used for the acute treatment of migraine; and
  3. For ubrogepant (Ubrelvy™), zavegepant (Zavzpret™), lasmiditan (Reyvow®) only, will not be used for preventative treatment of migraine; and 
  4. Member is 18 years of age or older; and
  5. Inadequate response or inability to tolerate two triptans (e.g., eletriptan, rizatriptan, sumatriptan); and
  6. If the member has 4 or more headache days per month, the member must be on current treatment or have inability to tolerate one of the following:
    1. Elavil (amitriptyline) or Effexor (venlafaxine); or
    2. Depakote/Depakote ER (divalproex sodium) or Topamax (topiramate); or
    3. Beta blocker (i.e., atenolol, propranolol, nadolol, timolol, or metoprolol); or
    4. Atacand (candesartan); and
  7. Prescribed by or in consultation with one of the following specialists:
    1. Neurologist; or
    2. Pain specialist; or
    3. Headache specialist certified by the United Council of Neurologic Subspecialties; and
  8. Medication will not be used in combination with another CGRP antagonist for the acute treatment of migraines; and
  9. For Lasmiditan (Reyvow®) and zavegepant (Zavzpret) only, inadequate response or inability to tolerate BOTH rimegepant (Nurtec™ ODT) and ubrogepant (Ubrelvy™) 

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: Rimegepant (Nurtec™ ODT), ubrogepant (Ubrelvy™), zavegepant (Zavzpret) or lasmiditan (Reyvow®) is reapproved when all of the following are met:

  1. Member has experienced a positive response to therapy (e.g., reduction in pain, photophobia, phonophobia, nausea); and
  2. For ubrogepant (Ubrelvy™), zavegepant (Zavzpret™), lasmiditan (Reyvow®) only, will not be used for preventative treatment of migraine; and
  3. Prescribed by or in consultation with one of the following specialists:
    1. Neurologist; or
    2. Pain specialist; or
    3. Headache specialist certified by the United Council of Neurologic Subspecialties; and
  4. Medication will not be used in combination with another CGRP antagonist for the acute treatment of migraines

Reauthorization duration: 2 years

Preventative Treatment of Episodic or Chronic Migraine with Injectable CGRP Antagonists
INITIAL CRITERIA: Erenumab (Aimovig™), fremanezumab (Ajovy™), or galcanezumab (Emgality™) 120mg/ml is approved when ALL of the following are met:

  1. Prescribed by or in consultation with one of the following specialists:
    1. Neurologist; or
    2. Pain specialist; or
    3. Headache specialist certified by the United Council for Neurologic Subspecialties, and
  2. Member is 18 years of age or older; and
  3. ONE of the following:
    1. Diagnosis of episodic migraines defined as 4-14 headache days per month and inadequate response or inability to tolerate at least a two-month trial of TWO of the following prophylactic medications:
      1. Topiramate
      2. Divalproex sodium/ valproic acid
      3. Beta-blocker: metoprolol, propranolol, timolol, atenolol, nadolol
      4. Tricyclic antidepressants: amitriptyline, nortriptyline
      5. SNRI antidepressants: venlafaxine, duloxetine; or
      6. Candesartan (Atacand); or
    2. Diagnosis of chronic migraines defined as 15 or more headache days per month and inadequate response or inability to tolerate at least a two-month trial of TWO of the following prophylactic medications:
      1. Topiramate
      2. Divalproex sodium/valproic acid
      3. Beta-blocker: metoprolol, propranolol, timolol, atenolol, nadolol
      4. Tricyclic antidepressants: amitriptyline, nortriptyline
      5. SNRI antidepressants: venlafaxine, duloxetine; or
      6. Trial of additional prophylactic medications does not apply if member has previously been treated with Onabotuliniumtoxin A (Botox) for migraines; and
  4. Medication overuse headache has been considered and potentially offending medication(s) have been discontinued; and
  5. Medication will not be used in combination with another CGRP inhibitor for the preventive treatment of migraines; and
  6. For galcanezumab (Emgality™ 120mg/ml) only, inadequate response or inability to tolerate BOTH erenumab (Aimovig™) and fremanezumab (Ajovy™). 

Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Erenumab (Aimovig™), fremanezumab (Ajovy™), or galcanezuma (Emgality™) 120mg/ml is re-approved when ALL of the following are met:

  1. Prescribed by or in consultation with one of the following specialists:
    1. Neurologist; or
    2. Pain specialist; or
    3. Headache specialist certified by the United Council for Neurologic Subspecialties, and
  2. Documentation of response to therapy as defined by 50% reduction in headache days per month from baseline (defined as at least 4 hours duration and moderate intensity); and
  3. For galcanezumab (Emgality™ 120mg/ml) only, inadequate response or inability to tolerate BOTH erenumab (Aimovig™) and fremanezumab (Ajovy™); and
  4. Use of acute migraine medication (e.g., nonsteroidal anti-inflammatory drugs (NSAID) (e.g., ibuprofen, naproxen), triptans (e.g., eletriptan, rizatriptan, sumatriptan) has decreased since the start of CGRP therapy; and
  5. For Chronic migraine only: member continues to be monitored for medication overuse headache (MOH); and
  6. Medication will not be used in combination with another CGRP inhibitor for the preventive treatment of migraines

Reauthorization duration: 12 months

Preventative Treatment of Episodic Migraines with Oral CGRP Antagonist
INITIAL CRITERIA: Rimegepant (Nurtec™ ODT) or atogepant (Qulipta™) is approved when all of the following are met:

  1. Both of the following:
    1. Diagnosis of episodic migraines; and
    2. One of the following:
      1. For Nurtec ODT only, member has 4 to 18 migraine days per month, but no more than 18 headache days per month; or
      2. For Qulipta only, Member has 4 to 14 migraine days per month, but no more than 14 headache days per month; and
  2. Member is 18 years of age or older; and
  3. Two of the following:
    1. Inadequate response or inability to tolerate at least a two-month trial of Elavil (amitriptyline) or Effexor (venlafaxine); or
    2. Inadequate response or inability to tolerate at least a two-month trial of Depakote/Depakote ER (divalproex sodium) or Topamax (topiramate); or
    3. Inadequate response or inability to tolerate at least a two-month trial of one of the following beta blockers: atenolol, propranolol, nadolol, timolol, or metoprolol; and
    4. Inadequate response or inability to tolerate at least a two-month trial of Atacand (candesartan); and
  4. Prescribed by or in consultation with one of the following specialists:
    1. Neurologist; or
    2. Pain specialist; or
    3. Headache specialist certified by the United Council for Neurologic Subspecialties; and
  5. Medication will not be used in combination with another CGRP antagonist for the preventative treatment of migraines

 
Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Rimegepant (Nurtec™ ODT) or atogepant (Qulipta™) is re-approved when all of the following are met:

  1. Member has experienced a positive response to therapy, demonstrated by a reduction in headache frequency and/or intensity; and
  2. Use of acute migraine medications [e.g., nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen, naproxen), triptans (e.g., eletriptan, rizatriptan, sumatriptan)] has decreased since the start of CGRP therapy; and
  3. Prescribed by or in consultation with one of the following specialists:
    1. Neurologist; or
    2. Pain specialist; or
    3. Headache specialist certified by the United Council for Neurologic Subspecialties; and
  4. Medication will not be used in combination with another CGRP antagonist for the preventative treatment of migraines

Reauthorization duration: 2 years

Preventive treatment of Chronic Migraine with Oral CGRP Antagonist
INITIAL CRITERIA: Atogepant (Qulipta™) is approved when all of the following are met:

  1. Diagnosis of chronic migraines defined as 15 or more headache days per month, of which at least 8 must be migraine days for at least 3 months; and
  2. Inadequate response or inability to tolerate at least two-month trial of TWO of the following prophylactic medications:
    1. Tricyclic antidepressants: amitriptyline, nortriptyline
    2. Topiramate
    3. Divalproex sodium/valproic acid
    4. Beta blocker: metoprolol, propranolol, timolol, atenolol, nadolol
    5. SNRI antidepressants; venlafaxine, duloxetine
    6. Candesartan (Atacand)
  3. Trial of additional prophylactic medications does not apply if member has previously been treated with Onabotuliniumtoxin A (Botox) for migraines; and
    1. Prescribed by or in consultation with one of the following specialists:
    2. Neurologist; or
    3. Pain specialist; or
    4. Headache specialist certified by the United Council for Neurologic Subspecialties; and
  4. Member is 18 years of age or older; and
  5. Medication will not be used in combination with another CGRP inhibitor for the preventative treatment of migraines; and
  6. Medication overuse headache has been considered and potentially offending medication(s) have been discontinued

Initial authorization duration: 6 months


REAUTHORIZATION CRITERIA: Atogepant (Qulipta™) is re-approved when all of the following are met:

  1. Member has experienced a positive response to therapy, demonstrated by a reduction in headache frequency and/or intensity; and
  2. Use of acute migraine medications [e.g., nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen, naproxen), triptans (e.g., eletriptan, rizatriptan, sumatriptan)] has decreased since the start of CGRP therapy; and
  3. Member continues to be monitored for medication overuse headache (MOH); and
  4. Prescribed by or in consultation with one of the following specialists:
    1. Neurologist; or
    2. Pain specialist; or
    3. Headache specialist certified by the United Council for Neurologic Subspecialties; and
  5. Medication will not be used in combination with another CGRP inhibitor for the preventative treatment of migraines

Reauthorization duration: 2 years

Episodic Cluster Headaches
INITIAL CRITERIA: Galcanezumab (Emgality™) 100mg/ml is approved when ALL of the following are met:

  1. Diagnosis of episodic cluster headache; and
  2. Member has experienced at least 2 cluster periods lasting 7 days to 365 days, separated by pain-free periods lasting at least three months; and
  3. Member is 18 years of age or older; and
  4. Prescribed by or in consultation with one of the following specialists:
    1. Neurologist; or
    2. Pain specialist; or
    3. Headache specialist certified by united council for neurologic subspecialties, or pain specialist; and
  5. Medication will not be used in combination with another CGRP antagonist

Initial authorization duration: 3 months

REAUTHORIZATION CRITERIA: Galcanezumab (Emgality™) 100mg/ml is re-approved when ALL of the following are met:

  1. Member has experienced a positive clinical response to therapy, demonstrated by a reduction in headache frequency and/or intensity; and
  2. Prescribed by or in consultation with one of the following specialists:
    1. Neurologist; or
    2. Pain specialist; or
    3. Headache specialist certified by united council for neurologic subspecialties, or pain specialist; and
  3. Medication will not be used in combination with another CGRP antagonist

Reauthorization duration: 12 months


Migranal®, D.H.E 45®, Trudhesa™

WARNING: PERIPHERAL ISCHEMIA FOLLOWING COADMINISTRATION WITH POTENT CYP3A4 INHIBITORS

Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine with strong CYP3A4 inhibitors. Because CYP3A4 inhibition elevates the serum levels of dihydroergotamine, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of TRUDHESA with strong CYP3A4 inhibitors is contraindicated.

Treximet®

WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.

TREXIMET is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.


DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T114718, Migraine in Adults; [updated 2018 Nov 30, cited 2022 April 01]. Available from https://www.dynamed.com/topics/dmp~AN~T114718.

 

MAXALT, MAXALT-MLT (rizatriptan) [package insert]. Kenilworth, NJ: GlaxoSmithKline. September 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d93286f5-99f7-4dc5-aa9d-ad73ab8490db. Accessed April 17, 2024.

 

Amerge (naratriptan) [package insert]. Research Triangle Park, NC: GlaxoSmithKline. October 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=13f4a8ec-75a3-4c51-b3bc-6244f3c79e95&type=display. Accessed April 17, 2024.

 

Frova (frovatriptan) [package insert]. Dublin, IE: Endo Pharmaceuticals, Inc.. August 2018. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c0703630-9ce8-4259-841e-71fd2019fa66. Accessed April 17, 2024.

 

Imitrex (sumatriptan) [package insert]. Research Triangle Park, NC: GlaxoSmithKline. December 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=584abe73-8290-4484-ff8e-5890831c095e. Accessed April 17, 2024.

 

Tsoymra (sumatriptan) [package insert]. Bridgewater, NJ: Promius Pharma, LLC. January 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7260d567-3824-230d-836d-8065302baaec. Accessed April 17, 2024.

 

Onztra Xsail (sumatriptan) [package insert]. Morristown, NJ: Currax Pharmaceuticals LLC. July 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a8a9889e-69b9-4a57-b8c0-d40b1025c559. Accessed April 17, 2024.

 

Zembrace SymTouch (sumatriptan) [package insert]. Bridgewater, NJ: Promius Pharma, LLC. June 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d565763d-b740-411d-bbb4-13536017d634. Accessed April 17, 2024.

 

Relpax (eletriptan) [package insert]. Hoffman Estates, IL: Roerig. July 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=85745375-fcb6-4edc-b6db-a77b4a5f3e8c. Accessed April 17, 2024.

 

Zomig, Zomig-ZMT (zolmitriptan) [package insert]. Bridgewater Township, NJ: Amneal Pharmaceuticals. May 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=df93b636-103f-4fb5-26b6-50f639e29b1d. Accessed April 17, 2024.

 

Treximet (sumatriptan succinate and naproxen sodium) [package insert]. Morristown, NJ: Currax Pharmaceuticals LLC. May 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=42ddf376-8dc0-4236-be2a-0c6ae92ece04. Accessed April 17, 2024.

 

D.H.E 45 (dihydroergotamine mesylate) [package insert]. Bridgewater Township, NJ: Bausch Health US, LLC. May 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fe826e6a-75c8-43ed-9c36-f8263ec35aff. Accessed April 17, 2024.

 

Migranal (dihydroergotamine mesylate) [package insert]. Bridgewater Township, NJ: Bausch Health US, LLC. July 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a24befa8-b952-48ac-942a-379585250782. Accessed April 17, 2024.

 

Nurtec ODT (rimegepant) [package insert]. New Haven, CT: Biohaven Pharmaceuticals, Inc. June 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9ef08e09-1098-35cc-e053-2a95a90a3e1d. Accessed April 17, 2024.

 

Ubrelvy (ubrogepant) [package insert]. Irvine, CA: Allergan, Inc. March 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fd9f9458-fd96-4688-be3f-f77b3d1af6ab. Accessed April 17, 2024.

 

Reyvow (lasmiditan) [package insert]. Indianapolis, IN: Eli Lilly and Company. April 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aea3358c-ff41-4490-9e6d-c7bf7b3de13f. Accessed April 17, 2024.

 

Aimovig (erenumab-aooe) [package insert]. Thousand Oaks, CA: Amgen Inc. May 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b998ed05-94b0-47fd-b28f-cddd1e128fd8. Accessed April 17, 2024.

 

Ajovy (fremanezumab-vfrm) [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc. June 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=98e344ea-5916-4947-b6f2-4a76ccc04b6b. Accessed April 17, 2024.

 

DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T116292, Cluster Headache; [updated 2018 Nov 30, cited 2022 April 01]. Available from https://www.dynamed.com/topics/dmp~AN~T116292.

 

Emgality (galcanezumab-gnlm) [package insert]. Indianapolis, IN: Eli Lilly and Company. September 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=33a147be-233a-40e8-a55e-e40936e28db0 Accessed April 17, 2024.

 

Qulipta™ (atogepant) [package insert]. Dublin, Ireland: AbbVie. June 2023. Available at: https://www.rxabbvie.com/pdf/QULIPTA_pi.pdf. Accessed April 17, 2024.

 

Trudhesa™ (dihydroergotamine mesylate nasal spray) [package insert]. Seattle, WA: Impel NeuroPharma Inc. September 2021. Available from: https://www.trudhesa.com/trudhesa-prescribing-information.pdf. Accessed April 17, 2024.


Zavzpret™ (zavegepant) [package insert]. New York, NY: Pfizer Inc. March 2023. Available from: https://labeling.pfizer.com/ShowLabeling.aspx?id=19471. Accessed April 17, 2024


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Rx.01.33 Off Label Use

Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit


Brand NameGeneric Name
Maxalt®/Maxalt® MLTRizatriptan
Amerge®Naratriptan
Frova®Frovatriptan
Imitrex®, Tosymra®, Onzetra® Xsail, Zembrace® SymtouchSumatriptan
Relpax®Eletriptan
Zomig®/ Zomig® ZMTZolmitriptan
Treximet®Sumatriptan/naproxen
D.H.E. 45®, Migranal®, Trudhesa™Dihydroergotamine mesylate
Nurtec™ ODTRimegepant
Ubrelvy™Ubrogepant
Reyvow®Lasmiditan
Aimovig™Erenumab
Ajovy™Fremanezumab
Emgality™Galcanezumab
Qulipta™Atogepant
Zavzpret™zavegepant​

Maxalt®/Maxalt® MLT, Amerge®, Frova®, Imitrex®, Tosymra®, Onzetra® Xsail, Zembrace® Symtouch, Relpax®, Zomig®/ Zomig® ZMT, Treximet®, D.H.E. 45®, Migranal®, Trudhesa™, Nurtec™ ODT, Ubrelvy™, Reyvow®, Aimovig™, Ajovy™, Emgality™, Qulipta™, Zavzpret™rizatriptan, naratriptan, frovatriptan, sumatriptan, eletriptan, zolmitriptan, sumatriptan/naproxen, dihydroergotamine mesylate, rimegepant, ubrogepant, lasmiditan, erenumab, fremanezumab, galcanezumab, atogepant, zavegepant
403
  
7/1/2024Rx.01.278CommercialOyenusi, OluwadamilolaQ1-2024
Friedreich’s ataxia is a progressive neurodegenerative disorder that causes progressive damage to the central nervous system. This is a rare disease that is caused by a mutation in the Frataxin (FXN) gene. A mutation in this gene causes mitochondrial dysfunction which causes iron accumulation and generation of a reactive oxygen species. In doing so, oxidative stress builds up in the body and causes cell damage. Symptoms of Friedreich’s ataxia include: trouble walking, tiredness, loss of reflexes, slow/slurred speech, hearing loss, loss of sensation, and shortness of breath.

Omaveloxolone belongs to a therapeutic drug class known as Nrf2 Pathway Activators which are known to reduce oxidative stress. In patients that have ataxia, Nrf2 levels are lower than normal. By taking omaveloxolone the Nrf2 translocates to the nucleus which in turn lowers oxidative stress in patients. Oxidative stress plays a role in several conditions in the body including neurodegenerative diseases. Thus, by lowering oxidative stress, symptoms associated with Freidrich’s ataxia can be reduced.

Skyclarys® is indicated for Freidrich’s ataxia in adults and adolescents aged 16 and older.  

The intent of this policy is to communicate the medical necessity criteria for Omaveloxolone (Skyclarys®) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA: Omaveloxolone (Skyclarys®) is approved when all of the following are met:

  1. Diagnosis of Friedreich ataxia as confirmed via genetic testing demonstrating mutation in FXN gene; and
  2. Member has a Modified Friedreich's Ataxia Rating Scale (mFARS) score of greater than or equal to 20 and less than or equal to 80; and
  3. Member has B-type natriuretic peptide value less than or equal to 200 pg/ml; and
  4. Member is 16 years of age or older; and
  5. Prescribed by or in consultation with one of the following:
    1. Neurologist; or
    2. Neurogeneticist; or
    3. Physiatrist (Physical Medicine and Rehabilitation Specialist)

Initial authorization duration: 1 year
 
CONTINUATION CRITERIA: Omaveloxolone (Skyclarys®) is re-approved when BOTH of the following are met:

  1. Documentation of positive clinical response to therapy as evidenced by one of the following:
    1. A decrease in the rate of progression of Modified FA rating scale (mFARS) score; or
    2. An increase in peak work (in Watts/kg) during exercise testing from baseline; and
  2. Prescribed by or in consultation with one of the following:
    1. Neurologist; or
    2. Neurogeneticist; or
    3. Physiatrist (Physical Medicine and Rehabilitation Specialist)

Reauthorization duration: 1 year


N/A

Skyclarys (omaveloxolone) [package insert]. Plano, TX; Reata Pharmaceuticals. January 2024. Available from: https://www.skyclarys.com/docs/skyclarys_us_prescribing_information/. Accessed April 17, 2024.

Opal P. Friedreich ataxia. UpToDate. December 2023. Available at: https://www.uptodate.com. Accessed April 17, 2024.

Pizzino G, Irrera N, Cucinotta M, et al. Oxidative stress: Harms and benefits for human health. Oxidative medicine and cellular longevity. 2017. Accessed August 3, 2023. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551541/.


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Rx.01.33 Off Label Use
Brand NameGeneric Name
Skyclarys®Omaveloxolone

Skyclarys®Omaveloxolone
404
  
7/1/2024Rx.01.243CommercialOyenusi, OluwadamilolaQ1-2024
Spinal muscular atrophy (SMA) is characterized by degeneration of the anterior horn cells in the spinal cord and motor nuclei in the lower brainstem, which results in progressive muscle weakness and atrophy. The diagnosis of SMA should be suspected for any infant with unexplained weakness or hypotonia. Additional clues suggesting the diagnosis in infants, children, or adults include a history of motor difficulties, loss of motor skills, proximal muscle weakness, hyporeflexia or areflexia, tongue fasciculations, and signs of lower motor neuron disease on examination. These diseases classified as types 0 through 4, depending upon the age of onset and clinical course.

Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier designed to treat patients with spinal muscular atrophy (SMA) caused by mutations in chromosome 5q that lead to SMN protein deficiency. Using in vitro assays and studies in transgenic animal models of SMA, risdiplam was shown to increase exon 7 inclusion in SMN2 messenger ribonucleic acid (mRNA) transcripts and production of full-length SMN protein in the brain. In vitro and in vivo data indicate that risdiplam may cause alternative splicing of additional genes, including FOXM1 and MADD. FOXM1 and MADD are thought to be involved in cell cycle regulation and apoptosis, respectively, and have been identified as possible contributors to adverse effects seen in animals.

Evrysdi is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.

​The intent of this policy is to communicate the medical necessity criteria for Risdiplam (Evrysdi®) as provided under the member's prescription drug benefit. 




INITAL CRITERIA: Risdiplam (Evrysdi™) is approved when ALL of the following are met:

  1. Diagnosis of spinal muscular atrophy (SMA) type 1, 2 or 3; and
  2. BOTH of the following:
    1. The mutation or deletion of genes in chromosome 5q resulting in one of the following:
      1. Homozygous gene deletion or mutation (e.g., homozygous deletion of exon 7 at locus 5q13); or
      2. Compound heterozygous mutation (e.g., deletion of SMN1 exon 7 [allele 1] and mutation of SMN1 [allele 2]); and
    2. Member has at least 2 copies of SMN2; and 
  3. Prescribed by or in consultation with a neurologist or a psychiatrist with subspecialty certification in neuromuscular medicine; and
  4. Member is not to receive concomitant chronic survival motor neuron (SMN) modifying therapy for the treatment of SMA (e.g., Spinraza)

Initial authorization duration: 12 months

REAUTHORIZATION CRITERIA: Risdiplam (Evrysdi™) is re-approved when ALL of the following are met:

  1. Documentation of positive clinical response to therapy from pretreatment baseline status; and
  2. Prescribed by or in consultation with a neurologist or a psychiatrist with subspecialty certification in neuromuscular medicine; and
  3. Member is not to receive concomitant chronic survivor motor neuron (SMN) modifying therapy for the treatment of SMA (e.g., Spinraza)

Reauthorization duration: 2 years


N/A

Evrysdi™ (risdiplam) [prescribing information]. San Francisco, CA: Genentech, Inc; February 2024. Available from: https://www.gene.com/download/pdf/evrysdi_prescribing.pdf. Accessed April 17, 2024.

Bodamer, OA. Spinal muscular atrophy. In: UpToDate. July 2023. Available from: www.uptodate.com. Accessed April 17, 2024.

Day JW, Annoussamy M, Baranello G, et al. SUNFISH Part 2: 24-month efficacy outcomes of risdiplam (RG7916) treatment in patients with Type 2 or 3 spinal muscular atrophy (SMA). Presented at the 2020 Virtual SMA Research & Clinical Care Meeting.

Servais L, Baranello G, Masson R, et al. FIREFISH Part 2: Efficacy and safety of risdiplam (RG7916) in infants with Type 1 spinal muscular atrophy (SMA). Presented at the 2020 Virtual SMA Research & Clinical Care Meeting.

Markowitz JA, Sing P, Darras BT. Spinal muscular atrophy: a clinical and research update. Pediatr Neurol. 2012;46(1):1-12.

Wang CH, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007;22(8):1027-1049.

Bertini E DJ, Muhaizea A, et al. RAINBOWFISH: A Study of Risdiplam (RG7916) in Newborns with Presymptomatic Spinal Muscular Atrophy. Presented at: World Muscle Society; October 1–5, 2019; Copenhagen, Denmark.

Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. J Neuromuscul Dis. 2018;28(2):103-115. Page 723

Stolte B, Bois JM, Kizina K, et al. Minimal clinically important differences in functional motor scores in adults with spinal muscular atrophy. Eur. J. Neurol. 2020; 0:1-9.

Pera, M., Coratti, G., Mazzone, E., et al. (2019). Revised upper limb module for spinal muscular atrophy: 12 month changes. Muscle Nerve. Apr;59(4):426-430.

Kirschner J, Butoianu N, Goemans N, et al. European ad-hoc consensus statement on gene replacement therapy for spinal muscular atrophy. Eur J Paediatr Neurol. 2020. https://doi.org/10.1016/j.ejpn.2020.07.001


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Rx.01.33 Off Label Use​



Brand NameGeneric Name
Evrysdi™
Risdiplam

Evrysdi™Risdiplam
405
  
7/1/2024Rx.01.237CommercialOyenusi, OluwadamilolaQ1-2024
Neuromyelitis optica spectrum disorders (NMOSD), are inflammatory disorders of the central nervous system characterized by severe, immune-mediated demyelination and axonal damage predominantly targeting optic nerves and spinal cord. NMOSD can be distinguished from multiple sclerosis and other central nervous system inflammatory disorders by the unique presence of the disease-specific aquaporin-4 (AQP4) antibody, which plays a direct role in the pathogenesis of NMOSD.

Common features of NMOSD include acute attacks characterized by bilateral or rapidly sequential optic neuritis (leading to visual loss), acute transverse myelitis (often causing limb weakness and bladder dysfunction), and the area postrema syndrome (with intractable hiccups or nausea and vomiting).

The precise mechanism by which Satralizumab-mwge (Enspryng™) exerts therapeutic effects in NMOSD is unknown but is presumed to involve inhibition of IL-6-mediated signaling through binding to soluble and membrane-bound IL-6 receptors. Satralizumab-mwge (Enspryng™) is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

​The intent of this policy is to communicate the medical necessity criteria for Satralizumab-mwge (Enspryng™) as provided under the member's prescription drug benefit. 

INITAL CRITERIA: Satralizumab-mwge (Enspryng™) is approved when ALL of the following are met:

  1. Diagnosis of neuromyelitis optica spectrum disorder (NMOSD); and
  2. Member is anti-aquaporin-4 (AQP4) antibody positive; and
  3. Prescribed by or in consultation with a neurologist or ophthalmologist; and
  4. Member is 18 years of age or older


Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: Satralizumab-mwge (Enspryng™) is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years


N/A
Enspryng™ (satralizumab-mwge) [prescribing information]. San Francisco, CA: Genentech, Inc; March 2022. Available from: https://www.gene.com/download/pdf/enspryng_prescribing.pdf. Accessed April 17, 2024.

Glisson C. Neuromyelitis optica spectrum disorders. UpToDate website. Last updated August 2022. Available at: www.uptodate.com. Accessed April 17, 2024.

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Rx.01.33 Off Label Use​
Brand NameGeneric Name
Enspryng™Satralizumab-mwge

Enspryng™Satralizumab-mwge
406
  
7/1/2024Rx.01.209CommercialOyenusi, OluwadamilolaQ1-2024

Lennox-Gastaut syndrome: A form of severe epilepsy that begins in childhood. It is characterized by multiple types of seizures and intellectual disability. People with Lennox-Gastaut syndrome begin having frequent seizures in early childhood, usually between ages 3 and 5 years.

Dravet syndrome (DS): A severe form of epilepsy which appears during the first year of life characterized by frequent, prolonged seizures often triggered by high body temperature (hyperthermia), developmental delay, speech impairment, loss of full control of bodily movements, low muscle tone, sleep disturbances, and other health problems.

Epidiolex ® (cannabidiol (CBD)); the exact mechanism by which CBD produces its anticonvulsant effects is unknown. CBD may exert a cumulative anticonvulsant effect, modulating a number of endogenous systems including, but not limited to, neuronal inhibition (synaptic and extrasynaptic GABA channels), modulation of intracellular calcium (TRPV, VDAC, GPR55), and possible anti-inflammatory effects (adenosine).

Diacomit® (stripentol); the mechanism of action by which stripentol exerts its anticonvulsant effect in humans is unknown. Possible mechanisms of action include direct effects mediated through the gamma-aminobutyric acid (GABA)A receptor and indirect effects involving inhibition of cytochrome P450 activity with resulting increase in blood levels of clobazam and its active metabolite. 

Onfi® (clobazam); The exact mechanism of action for clobazam, a 1,5-benzodiazepine, is not fully understood but is thought to involve potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site of the GABAA receptor.​​​​


Banzel® (rufinamide); The precise mechanism(s) by which rufinamide exerts its antiepileptic effect is unknown. The results of in vitro studies suggest that the principal mechanism of action of rufinamide is modulation of the activity of sodium channels and, in particular, prolongation of the inactive state of the channel. Rufinamide (≥ 1 μM) significantly slowed sodium channel recovery from inactivation after a prolonged prepulse in cultured cortical neurons, and limited sustained repetitive firing of sodium-dependent action potentials (EC50 of 3.8 μM).

​

Fintepla® (fenfluramine): The mechanisms by which fenfluramine exerts its therapeutic effects in the treatment of seizures associated with Dravet syndrome are unknown. Fenfluramine and the metabolite, norfenfluramine, increase extracellular levels of serotonin through interaction with serotonin transporter proteins, and exhibit agonist activity at serotonin 5HT-2 receptors.

Sabril® (vigabatrin): The precise mechanism of vigabatrin's anti-seizure effect is unknown, but it is believed to be the result of its action as an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the metabolism of the inhibitory neurotransmitter GABA. This action results in increased levels of GABA in the central nervous system.

Epidiolex ® is indicated for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex in patients 1 year of age and older.

Diacomit® is indicated for the treatment of seizures associated with Dravet syndrome in patients 6 months of age and older and weighing 7 kg or more taking clobazam. There are no clinical data to support the use of Diacomit® as monotherapy in Dravet syndrome

Onfi® and Sympazan® are indicated for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients2 years of age or older.

Banzel® indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome (LGS) in pediatric patients 1 year of age and older, and in adults.

Fintepla® (fenfluramine) is indicated for the treatment of seizures associated with Dravet syndrome  and Lennox-Gastaut syndrome in patients 2 years of age and older.

Sabril® is indicated as monotherapy for pediatric patients with infantile spasms 1 month to 2 years of age for whom the potential benefits outweigh the potential risk of vision loss and as adjunctive therapy for adults and pediatric patients 2 years of age and older with refractory complex partial seizures who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss


The intent of this policy is to communicate the medical necessity criteria for Epidiolex ® (cannabidiol),Diacomit® (stiripentol), Onfi®, Sympazan® (clobazam), Banzel® (rufinamide), Fintepla® (fenfluramine), and Vigabatrin (Sabril®) as provided under the member's prescription drug benefit. 

Dravet Syndrome
INITIAL CRITERIA: Cannabidiol (Epidiolex) is approved when ALL of the following are met:

  1. Member is 1 years of age or older; and
  2. Baseline CBC, serum transaminases and total bilirubin obtained prior to initiating therapy; and
  3. Diagnosis of Dravet syndrome; and
  4. Inadequate response or inability to tolerate ONE of the following:
    1. Clobazam*; or
    2. Valproic acid; or
    3. Levetiracetam; o
    4. Topiramate; and
  5. Documentation of concurrent use with additional anti-epileptic(s); and
  6. Prescribed by or in consultation with a neurologist  

INITIAL CRITERIA: Stiripentol (Diacomit®) is approved when ALL of the following are met:

  1. Diagnosis of seizures associated with Dravet syndrome; and
  2. Member is 6 months of age or older and weighing 7kg or more; and
  3. Used in combination with clobazam*; and
  4. Prescribed by or in consultation with a neurologist

 
INITIAL CRITERIA: Clobazam (Onfi®, Sympazan®) tablets, films, or oral suspension is approved when ALL of the following are met:

  1. Member is 6 months of age or older and weighs greater than or equal to 7 kg; and
  2. Diagnosis of seizures associated with Dravet Syndrome (DS); and
  3. Used in combination with Diacomit (Stiripentol); and
  4. Prescribed by or in consultation with a neurologist; and
  5. For brand Onfi® and brand Sympazan® only, inadequate response or inability to tolerate generic clobazam tablets or oral suspension

 
INITIAL CRITERIA: Fenfluramine (Fintepla®) is approved when ALL of the following are met:

  1. Diagnosis of Dravet Syndrome; and
  2. Member is 2 years of age or older; and
  3. Inadequate response or inability to tolerate ONE of the following:
    1. Clobazam*; or
    2. Valproic acid; or
    3. Divalproex sodium; or
    4. Topiramate; or
    5. Levetiracetam; and
  4. Prescribed by or in consultation with a neurologist

 
Initial authorization duration: 2 years 


CONTINUATION CRITERIA: Cannabidiol (Epidiolex®), Stiripentol (Diacomit®), clobazam (Onfi®, Sympazan®), or fenfluramine (Fintepla®) is re-approved when ALL of the following are met:

  1. Documentation of reduction in seizure activity or intensity; and
  2. Stiripentol (Diacomit®) only, used in combination with clobazam*; and
  3. Prescribed by or in consultation with a neurologist

Continuation authorization duration: 2 years

Lennox-Gastaut Syndrome (LGS)
INITIAL CRITERIA: Cannabidiol (Epidiolex®) is approved when ALL of the following are met:

  1. Member is 1 years of age or older; and
  2. Baseline CBC, serum transaminases and total bilirubin obtained prior to initiating therapy; and
  3. Diagnosis of Lennox-Gastaut syndrome (LGS); and
  4. Inadequate response or inability to tolerate ONE of the following:
    1. Valproic acid; or 
    2. Lamotrigine; or
    3. Topiramate; or
    4. Felbamate; or
    5. Rufinamide*; or
    6. Clobazam*; and
  5. Documentation of concurrent use with additional anti-epileptic(s); and
  6. Prescribed by or in consultation with a neurologist

INITIAL CRITERIA: Rufinamide (Banzel®) tablet or suspension is approved when ALL of the following are met:

  1. Diagnosis of seizures associated with Lennox-Gastaut Syndrome (LGS); and
  2. Used as adjunctive therapy; and
  3. Member is 1 year of age or older; and
  4. Inadequate response or inability to tolerate ONE of the following generics:
    1. Valproic acid; or
    2. Lamotrigine; or
    3. Topiramate; or
    4. Felbamate; or
    5. Clobazam*; and
  5. Prescribed by or in consultation with a neurologist; and
  6. For rufinamide (Banzel®) suspension only; ONE of the following:
    1. Drug will be administered via nasogastric or gastronomy tube; or
    2. Member is unable to swallow an intact capsule or tablet

INITIAL CRITERIA: Fenfluramine (Fintepla®) is approved when ALL of the following are met: 

  1. Diagnosis of seizures associated with Lennox-Gastaut Syndrome (LGS); and 
  2. Member is 2 years of age or older; and 
  3. Inadequate response or inability to tolerate ONE of the following generics: 
    1. Valproic acid; or 
    2. Lamotrigine; or 
    3. Topiramate; or 
    4. Felbamate; or 
    5. Clobazam; and
  4. Prescribed by or in consultation with a neurologist

Initial authorization duration: 2 years

INITIAL CRITERIA: Clobazam (Onfi®, Sympazan®) tablets, films or oral suspension is approved when ALL of the following are met: 

  1. Member is 2 years of age and older; and 
  2. Diagnosis of seizure associated with Lennox-Gastaut Syndrome; and 
  3. Used as adjunctive therapy; and
  4. Prescribed by or in consultation with a neurologist; and 
  5. For Brand Onfi® and brand Sympazan® only, inadequate response or inability to tolerate generic clobazam tablets or oral suspension

 
Initial authorization duration: 2 years

CONTINUATION CRITERIA: Cannabidiol (Epidiolex®), clobazam (Onfi®, Sympazan®), rufinamide (Banzel®), or fenfluramine (Fintepla®) is re-approved when there is documentation of reduction in seizure activity or intensity.

Continuation authorization duration: 2 years
 
Seizures associated with tuberous sclerosis complex
INITIAL CRITERIA: Cannabidiol (Epidiolex®) is approved when ALL of the following are met:

  1. Member is 1 years of age or older; and
  2. Baseline CBC, serum transaminases and total bilirubin obtained prior to initiating therapy; and
  3. Diagnosis of seizures associated with tuberous sclerosis complex; and
  4. Inadequate response or inability to tolerate ONE of the following:
    1. Vigabatrin*; or
    2. Carbamazepine; or
    3. Oxcarbazepine; and
  5. Documentation of concurrent use with additional anti-epileptic(s); and
  6. Prescribed by or in consultation with a neurologist

Initial authorization duration: 2 years

CONTINUATION CRITERIA: Cannabidiol (Epidiolex®) is re-approved when there is documentation of reduction in seizure activity or intensity.

Continuation authorization duration: 2 years


Refractory complex partial seizure or infantile spasms
INITIAL CRITERIA: Vigabatrin (Sabril®) is approved when ALL of the following are met:

  1. One of the following:
    1. ALL of the following:
      1. Diagnosis of refractory complex partial seizures as adjunctive therapy; and
      2. Member is 2 years of age or older; and
      3. Used as adjunct therapy; or

    2. BOTH of the following:

      1. Diagnosis of infantile spasms; and
      2. Member is 1 month to 2 years of age; and
  2. For brand Sabril® only, inadequate response or inability to tolerate generic vigabatrin or vigadrone; and
  3. Prescribed by or in consultation with a neurologist

Initial authorization duration: 2 years 

CONTINUATION CRITERIA: Vigabatrin (Sabril®) is re-approved when there is documentation of reduction in seizure activity of intensity.
Continuation authorization duration: 2 years

*Please note: prior authorization required


Onfi®, Sympazan® (clobazam): Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation. The use of benzodiazepines, including ONFI and SYMPAZAN, , exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Before prescribing ONFI and SYMPAZAN,  and throughout treatment, assess each patient's risk for abuse, misuse, and addiction. Abrupt discontinuation or rapid dosage reduction of ONFI and SYMPAZAN,  after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue ONFI and SYMPAZAN,  or reduce the dosage.

Fintepla® (fenfluramine): There is an association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine (the active ingredient in Fintepla®), and valvular heart disease and pulmonary arterial hypertension. Echocardiogram assessments are required before, during, and after treatment with Fintepla®. Fintepla® is available only through a restricted program called the Fintepla® REMS.

Sabril® (vigabatrin): SABRIL causes progressive and permanent bilateral concentric visual field constriction in a high percentage of patients. In some cases, SABRIL may also reduce visual acuity. Risk increases with total dose and duration of use, but no exposure to SABRIL is known that is free of risk of vision loss. Risk of new and worsening vision loss continues as long as SABRIL is used, and possibly after discontinuing SABRIL. Unless a patient is formally exempted, periodic vision assessment is required for patients on SABRIL. However, this assessment cannot always prevent vision damage. SABRIL can cause permanent vision loss. SABRIL is available only through a restricted program called the SHARE Program.​


Banzel® (rufinamide) [prescribing information]. Woodcliff Lake, NJ: Eisai Inc.; December 2022. Available from: https://www.banzel.com/~/media/Files/BanzelPatient/BanzelPI.pdf. Accessed April 17, 2024.
 

Diacomit® (stripentol) [package insert]. Beauvais, France. Biocodex.  July 2022. Available from: https://www.diacomit.com/pdf/PI-Diacomit-2018.pdf. Accessed April 17, 2024.
 

"Dravet Syndrome." Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services, December 2016, rarediseases.info.nih.gov/diseases/10430/dravet-syndrome.

 

"Epidiolex (Cannabidiol) Dosing, Indications, Interactions, Adverse Effects, and More." Medscape Drugs &amp; Diseases - Comprehensive Peer-Reviewed Medical Condition, Surgery, and Clinical Procedure Articles with Symptoms, Diagnosis, Staging, Treatment, Drugs and Medications, Prognosis, Follow-up, and Pictures, 26 June 2018, reference.medscape.com/drug/epidiolex-cannabidiol-1000225#10.

 

Epidiolex® (cannabidiol) [package insert]. Cambridge, United Kingdom. GW Pharmaceuticals Co. Ltd. March 2024. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8bf27097-4870-43fb-94f0-f3d0871d1eec&type=display. Accessed April 17, 2024.
 

Fintepla® (fenfluramine) oral solution [prescribing information]. Emeryville, CA: Zogenix, Inc.; December 2023. Available from: https://www.fintepla.com/pdf/Fintepla-prescribing-information.pdf. Accessed April 17, 2024.
 

"Lennox-Gastaut Syndrome - Genetics Home Reference - NIH." U.S. National Library of Medicine, National Institutes of Health, July 2019, ghr.nlm.nih.gov/condition/lennox-gastaut-syndrome.

 

Onfi® (clobazam) [prescribing information]. Deerfield, IL: Lundbeck; March 2024. Available from: https://www.lundbeck.com/upload/us/files/pdf/Products/ONFI_PI_US_EN.pdf. Accessed April 17, 2024.
 

Sabril® (vigabatrin) [prescribing information]. Deerfield, IL: Lundbeck; October 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020427s010s011s012,022006s011s012s013lbl.pdf. Accessed April 17, 2024.
 

Sympazan® (clobazam) [prescribing information]. Warren, NJ: Aquestive Therapeutics; March 2021. Available from: https://www.sympazan.com/pdfs/pi.pdf. Accessed April 17, 2024.



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​Off-Label Use Rx.01.33
​Applicable Age Edits Rx.01.2
Brand NameGeneric Name
Epidiolex®Cannabidiol
Diacomit®Stiripentol
Onfi®, Sympazan®
Clobazam
Banzel®Rufinamide
Fintepla®Fenfluramine

​Sabril®
​Vigabatrin

Epidiolex ®, Diacomit®, Onfi®, Sympazan®, Banzel®, Fintepla®, Sabril®cannabidiol, stiripentol, clobazam, rufinamide, fenfluramine, Vigabatrin
407
  
7/1/2024Rx.01.271CommercialOyenusi, OluwadamilolaQ1-2024
Human papillomavirus (HPV) is a common cause of cutaneous and mucosal infection. Condylomata acuminata (CA; singular: condyloma acuminatum), also known as anogenital warts, are manifestations of HPV infection that occur in a subset of individuals with anogenital HPV infection. External CA typically manifest as soft papules or plaques on the external genitalia, perianal skin, perineum, or groin. For most patients, the presence of genital warts is concerning because of their cosmetic appearance, association with a sexually transmitted disease, bothersome symptoms, absence of a cure, and social stigma. Although treatment can eradicate the warts, disease recurrence is common and occurs in 20 to 30 percent of patients overall.

The mode of action of Veregen involved in the clearance of genital and perianal warts is unknown. In vitro, sinecatechins had anti-oxidative activity; the clinical significance of this finding is unknown.
 
Veregen is indicated for the topical treatment of external genital and perianal warts (Condylomata acuminata) in immunocompetent patients 18 years and older.

The intent of this policy is to communicate the medical necessity criteria for Sinecatechins (Veregen®) as provided under the member's prescription drug benefit.

Sinecatechins (Veregen®) is approved when all of the following are met:

  1. Diagnosis of Condylomata acuminata (external genital and perianal warts); and
  2. Member is immunocompetent; and
  3. Member is 18 years of age or older; and
  4. Inadequate response or inability to tolerate imiquimod (generic Aldara®)

Authorization duration: 4 months

Total duration of treatment is limited to 16 weeks per lifetime


N/A

Rosen T. Condylomata acuminata (anogenital warts) in adults: Epidemiology, pathogenesis, clinical features, and diagnosis. In: Post T, ed. UpToDate. December 2022. www.uptate.com. Accessed April 17, 2024..

 

Veregen® (Sinecatechins) [prescribing information]. Melville, New York: PharmaDerm®; February 2022. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2c1cd745-79ab-487d-b759-995794cedb92. Accessed April 17, 2024.​


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Rx.01.33 Off Label Use​
Brand NameGeneric Name
Veregen®Sinecatechins

Veregen®sinecatechins
408
  
7/1/2024Rx.01.274CommercialOyenusi, OluwadamilolaQ1-2024
Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder that involve many organ systems, including developmental delay and multiple benign hamartomas of the brain, eyes, heart, lung, liver, kidney, and skin. The expression of the disease varies substantially among individuals and within families. Some individuals with TSC may demonstrate only dermatologic features of the disease while others may develop more serious neurologic or systemic manifestations. Nearly all patients with TSC have one or more of the skin lesions characteristic of the disorder.

The mechanism of action of sirolimus in the treatment of angiofibroma associated with tuberous sclerosis is unknown. Tuberous sclerosis is associated with genetic defects in TSC1 and TSC2 which leads to the constitutive activation of mammalian target of rapamycin (mTOR). Sirolimus inhibits mTOR activation.

Hyftor™ is indicated for the treatment of facial angiofibroma associated with tuberous sclerosis in adults and pediatric patients 6 years of age and older.

The intent of this policy is to communicate the medical necessity criteria for Sirolimus topical gel (Hyftor™) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA: Sirolimus (Hyftor™) is approved when ALL of the following are met:

  1. Diagnosis of facial angiofibroma associated with tuberous sclerosis complex; and
  2. Member is 6 years of age or older; and
  3. Member is not a candidate for laser therapy or surgical treatments; and
  4. Prescribed by or in consultation with a dermatologist, neurologist, or geneticist

Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Sirolimus (Hyftor™) is re-approved with documentation of positive clinical response to therapy (e.g., improvement in size or redness of facial angiofibroma)

Reauthorization duration: 2 years


N/A

Randle S. Tuberous sclerosis complex: Management and prognosis. UpToDate. February 2024. Available from: uptodate.com. Accessed April 17, 2024.

HyftorTM (sirolimus) [package insert]. Bethesda, MD: Nobelpharma America, LLC; March 2022. Available at https://www.hyftor.com/wp-content/uploads/2022/04/Approved-PI.pdf. Accessed April 17, 2024.


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Rx.01.33 Off Label Use​
Brand NameGeneric Name
Hyftor™sirolimus

Hyftor™Sirolimus
409
  
7/1/2024Rx.01.222CommercialOyenusi, OluwadamilolaQ1-2024

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neuropsychiatric disorders of childhood and adolescences where symptoms often persist into adulthood. It is associated with significant impairment in occupational, academic, and social functioning. ADHD in adults is characterized by symptoms of inattention, impulsiveness, restlessness, executive dysfunction, and emotional dysregulation. Compared to adults with ADHD, symptoms of inattention, hyperactivity and impulsive behaviors are more prominent in children and adolescents.

Prescription stimulants are an integral part of treatment for attention deficit hyperactivity disorder (ADHD) but it is also one of the most frequently abused prescription drugs in the United States. In 2016, an estimated 5,647,000, or 2.1% of persons aged 12 and older, reported misuse of prescription stimulants in the past year. In 2017, a total of 10,333 deaths involving psychostimulants occurred, representing 14.7% of drug overdose deaths and a 37.0% increase from 2016 per the CDC.

The cumulative dose limit is based on the cumulative daily dose of drugs with the same active ingredient.  Prior authorization is required when the request exceeds the recommended dose for medications with that active ingredient outlined below:

High cumulative daily dose limit - This limit is in place to ensure alternative medications have been reviewed and potential adverse effects have been accessed.

Active ingredient

Medications impacted

(brands and generics)

High cumulative daily dose
Amphetamine

Adzenys® [XR ODT/ER]

Dyanavel® [XR]

Evekeo® [ODT]

60mg/day

Amphetamine/

Dextroamphetamine

Adderall® [IR/XR]

Mydayis®

60mg/day
Dextroamphetamine

Dexedrine®

Zenzedi®

ProCentra®

Xelstrym™

60mg/day
LisdexamfetamineVyvanse®70mg/day
MethamphetamineDesoxyn®60 mg/day
DexmethylphenidateFocalin® [IR/XR]40mg/day
Methylphenidate

Ritalin® [IR/LA]

Daytrana®

Cotempla®

Metadate® [ER/CD] Methylin®

Quillivant® XR

Concerta®

Aptensio® XR

QuilliChew® ER

Adhansia® XR

Jornay PM™

Methylphenidate (Relexxii®)

72mg/day
SerdexmethylphenidateAzstarys™52.3 mg/day

The intent of this policy is to communicate the medical necessity criteria for prescription stimulants under the member's prescription benefit when the cumulative dose of an active ingredient exceeds the limit set by the plan.

Doses above the high cumulative dose are approved when ALL of the following are met:

  1. Inadequate response or inability to tolerate an alternative active ingredient within the CNS stimulant drug class prior to increasing the dose beyond the cumulative high dose limit; and
  2. Member has been assessed for, and counseled by prescriber on ALL of the following:
    1. The risk for substance abuse; and
    2. The risk for cardiac related adverse events (i.e., hypertension); and
    3. The risk for new or worsening psychosis (i.e., maniac behavior); and
  3. Requests that exceed the cumulative daily dose for the total daily dose of the drug, dose frequency, or duration of therapy approved or recommended by the FDA or as stated in accepted compendia are considered off-label and are reviewed per Off-Label Use policy

Authorization duration: 12 months

INITIAL CRITERIA: Amphetamine (Evekeo®) is approved when ONE of the following is met:

  1. Diagnosis of narcolepsy and ALL of the following:
    1. Recommended by a neurologist or sleep specialist; and
    2. Inadequate response or inability to tolerate generic modafinil or armodafinil; and
    3. Diagnosis confirmed by ONE of the following tests:
      1. Polysomnography (PSG); or
      2. Multiple sleep latency test (MSLT); or
  2. Attention Deficit Disorder with Hyperactivity (ADHD) with inadequate response or inability to tolerate TWO of the following generic stimulant agents for ADHD:
    1. Methylphenidate
    2. Mixed amphetamine salts
    3. Dextroamphetamine
    4. Methamphetamine hydrochloride
    5. Dexmethylphenidate; or
  3. Exogenous Obesity:
    1. If member has weight loss rider please refer to Weight Loss Agents policy for approval criteria and duration; or
    2. If member does not have a weight loss agents rider; deny as benefit exclusion*

*Drugs that are used for weight loss are covered only with weight loss rider. 

Initial authorization duration: 2 years
 
REAUTHORIZATION CRITERIA: Amphetamine (Evekeo®) is re-approved when there is documentation of positive clinical response.
 
Reauthorization duration: 2 years
 
Quantity limit requests are approved when ONE of the following is met: (drug specific criteria below).

  1. Requests that exceed the cumulative daily dose, dose frequency, or duration of therapy approved or recommended by the FDA or as stated in accepted compendia1 are considered off-label and are reviewed per Off-Label Use policy, or
  2. Requests that do not exceed the cumulative daily dose, dose frequency or duration of therapy approved or recommended by the FDA or as stated in accepted compendia1: A quantity limit exceeding those listed in the following table is approved when ONE of the following is met:
    1. Documentation of the inability to reach the requested dose with higher strengths of commercially available dosage forms due to member specific characteristics (i.e., inability to swallow larger pills, malabsorption, presence of a feeding tube, etc.); or
    2. The requested dose is not commercially available; or
    3. The requested dose is used for titration or loading-dose purposes (one-time authorization)

1 Please refer to the Off-Label Use policy for definition of accepted compendia

Authorization duration: 2 years
Authorization duration for dose titration: 14 days

 

MedicationMaximum Quantity per dayQuantity limit per rolling 30 days, unless otherwise specified (tablets, capsules, mL)
Amphetamine (Adzenys XR®)130
Amphetamine (Adzenys ER®) 1.25mg/ml susp15 ml450
Dextroamphetamine/Amphetamine (Adderall®) 5mg, 7.5mg, 10mg, 12.5mg, 15mg and 20mg390
Dextroamphetamine/Amphetamine (Adderall®) 30mg260
Amphetamine/Dextroamphetamine ER (Mydayis™)130
Dextroamphetamine/Amphetamine (Adderall XR®) 5mg, 10mg, 15mg, 20mg, 25mg, 30mg130
Amphetamine (Dyanavel XR®) 2.5mg/ml Susp8mL240
Amphetamine (Dyanavel XR®) 5mg, 10mg, 15mg, 20mg tablets130
Dextroamphetamine sulfate (Dexedrine®) 5mg cap SA390
Dextroamphetamine sulfate (Dexedrine®) 10mg cap SA6180
Dextroamphetamine sulfate (Dexedrine®) 15mg cap SA4120
Dextroamphetamine sulfate 5mg tablet390
Dextroamphetamine sulfate 10mg tablet390
Dexmethylphenidate HCL (Focalin®) 2.5mg, 5mg, 10mg260
Dexmethylphenidate HCL (Focalin XR®) 5mg, 10mg, 15mg, 20mg, 25mg, 30mg, 35mg, 40mg130
Dextroamphetamine sulfate (Procentra®) 5mg/5ml solution601800
Dextroamphetamine (Xelstrym™) 13.5 MG/9HR, 18 MG/9HR, 4.5 MG/9HR, 9 MG/9HR130
Dextroamphetamine (Zenzedi®) 2.5mg, 5mg, 7.5mg, 10mg, 15mg, 20mg tablet390
Dextroamphetamine (Zenzedi®) 30mg tablet260
Amphetamine (Evekeo®) 5mg390
Amphetamine (Evekeo®) 10mg4120
Amphetamine (Evekeo® ODT)390
Lisdexamfetamine dimesylate (Vyvanse®) 20mg, 30mg, 40mg, 50mg, 60mg, 70mg130
Methylphenidate HCL ER 24HR (Adhansia™ XR) 25mg, 35mg, 45mg, 55mg, 70mg, 85mg130
Methylphenidate (Aptensio XR®)130
Methylphenidate HCL (Concerta®) 18mg, 27mg, 54mg130
Methylphenidate HCL (Concerta®) 36mg tablet ER260
Methylphenidate HCL ER 72mg
osmotic release tab		130
Methylphenidate (Relexxii®) tab ER osmotic release 45mg, 63mg130
Methylphenidate (Daytrana patch®) 10mg/9hr, 15mg/9hr, 20mg/9hr, 30mg/9hr130
Methamphetamine HCL (Desoxyn®) 5mg tablet5150
Methylphenidate HCL ER capsule (Jornay™ PM) 20mg, 40mg, 60mg, 80mg, 100mg130
Methylpenidate HCL (Metadate CD®) 10mg, 20mg, 30mg, 40mg, 50mg, 60mg130
Methylphenidate HCL (Metadate ER®) 10mg, 20mg tablet SA390
Methylphenidate HCL (Methylin®) 2.5mg, 10mg chewable tablet6180
Methylphenidate HCL (Methylin®) 5mg chewable tablet390
Methylphenidate HCL (Methylin®) 10mg/5ml30900
Methylphenidate HCL (Methylin®) 5mg/5ml601800
Methylphenidate HCL (Ritalin®) 5mg, 10mg, 20mg390
Methylphenidate HCL (Ritalin LA®) 10mg, 40mg capsule130
Methylphenidate HCL (Ritalin LA®) 20mg capsule390
Methylphenidate HCL (Ritalin LA®) 30mg capsule260
Methylphenidate (Quillichew ER®) 20mg, 30mg260
Methylphenidate (Quillichew ER®) 40mg130
Methylphenidate (Quillivant XR®) 5mg/mL12mL360
Methylphenidate ER disintegrating tabs (Cotempla®) 8.6mg, 17.3mg, 25.9mg130
Serdexmethylphenidate-dexmethylphenidate (Azstarys™)130

Adzenys XR-ODT™, Adzenys ER®, Adderall®, Adderall® XR, Adhansia XR™, Aptensio XR™, Azstarys™, Concerta®, Dyanavel® XR, Dexedrine®, Dextroamphetamine sulfate, Evekeo®, Focalin®, Focalin® XR, Jornay PM™, Metadate® CD/ER, methylphenidate ER, Mydayis®, QuilliChew ER™, Quillivant XR®, Ritalin®, Ritalin [LA]®, Zenzedi™, Vyvanse®, Cotempla®, Dexedrine® (dextroamphetamine), ProCentra®, Xelstrym™ 

  1. Abuse and dependence: CNS stimulants, other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence. Assess the risk the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy.

Methylin®, Ritalin®, Concerta®, Daytrana®, Relexxii®

  1. Drug dependence: should be given cautiously to patients with a history of drug dependence or alcoholism. Chronic, abusive use can lead to marked tolerance and psychological dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful supervision is required during drug withdrawal from abusive use since severe depression may occur. Withdrawal following chronic therapeutic use may unmask symptoms of the underlying disorder that may require follow-up.

Desoxyn®

  1. Methamphetamine has a high potential for abuse. It should thus be tried only in weight reduction programs for patients in whom alternative therapy has been ineffective. Administration of methamphetamine for prolonged periods of time in obesity may lead to drug dependence and must be avoided. Particular attention should be paid to the possibility of subjects obtaining methamphetamine for non-therapeutic use or distribution to others, and the drugs should be prescribed or dispensed sparingly. Misuse of methamphetamine may cause sudden death and serious cardiovascular adverse events.     

Adzenys ER® (amphetamine) [prescribing information]. Grand Prairie, TX: Neos Therapeutics; December 2017. Accessed April 17, 2024.

 

Adzenys XR-ODT™ (amphetamine) [prescribing information]. Grand Prairie, TX: Neos Therapeutics; February 2018. Accessed April 17, 2024.

 

Adderall® (dextroamphetamine/amphetamine) [prescribing information]. North Wales, PA: Teva Pharmaceuticals; July 2018. Accessed April 17, 2024.

 

Adderall XR® (dextroamphetamine/amphetamine) [prescribing information]. Social Circle, GA: Shire US Manufacturing Inc.; July 2019. Accessed April 17, 2024.

 

Adhansia XR™ (methylphenidate) [prescribing information]. Wilson, NC: Adlon Therapeutics L.P. July 2019. Accessed April 17, 2024.

 

American Psychiatry Association. Attention-Deficit/Hyperactivity Disorder. In: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, American Psychiatric Association, Arlington, VA 2013. P.59

 

Aptensio XR™ (methylphenidate) [prescribing information]. Coventry, RI: Rhodes Pharmaeuticals; June 2019. Accessed April 17, 2024.

 

Azstarys™ (serdexmethylphenidate and dexmethylphenidate) [prescribing information]. Grand Rapids, MI: Corium, Inc. June 2021. Accessed April 17, 2024.

 

Concerta® (methylphenidate) [prescribing information]. Horsham, PA: Janssen Pharmaceuticals, Inc; January 2017. Accessed April 17, 2024.

 

Cotempla XR-ODT® (methylphenidate extended-release orally disintegrating tablet) [prescribing information. Grand Prairie, TX: Neos Therapeutics Brands, LLC. June 2017. Accessed April 17, 2024.

 

Daytrana® patch (methylphenidate) [prescribing information]. New York, NY: Noven Therapeutics, LLC; October 2019. Accessed April 17, 2024.

 

Desoxyn® (methamphetamine HCL) [prescribing information]. Lebanon, NJ: Recordati Rare Diseases, Inc; March 2019. Accessed April 17, 2024.

 

Dexedrine® (dextroamphetamine) [prescribing information]. Horsham, PA: Amedra Pharmaceuticals LLC; March 2019. Accessed April 17, 2024.

 

Dextroamphetamine sulfate [prescribing information]. Morgantown, WV: Mylan Pharmaceuticals Inc.; 2015. Accessed April 17, 2024.

 

Dosing Psychotropics: How High Can We Go? TCPR, September 2007, Vol. 5, Issue 9, Complex Psychopharmacology

 

Dyanavel® XR (amphetamine) [prescribing information]. Monmouth Junction, NJ: Tris Pharma Inc; February 2019. Accessed April 17, 2024.

 

Evekeo® (amphetamine) [prescribing information]. Atlanta, GA: Arbor Pharmaceuticals, LLC. September 2016. Accessed April 17, 2024.

 

Evekeo® ODT (amphetamine) [prescribing information]. Atlanta, GA. Arbor Pharmaceuticals, LLC. March 2019.  Accessed April 17, 2024.

 

Fayyad J, De Graaf R, Kessler R, et al. Cross-national prevalence and correlates of adult attention-deficit hyperactivity disorders. Br J Psychiatry 2007; 190:420

 

Focalin® (dexmethylphenidate) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; November 2019. Accessed April 17, 2024.

 

Focalin XR® (dexmethylphenidate) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; November 2019. Accessed April 17, 2024.

 

Jornay PM™ (methylphenidate) [prescribing information]. Cherry Hill, NJ: Ironshore Pharmaceuticals, Inc. April 2019. Accessed April 17, 2024.

 

Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 2006; 163:716

 

Kariisa M, Scholl L, Wilson N, et. Al. Drug Overdose Deaths Involving Cocaine and Psychostimulants with Abuse Potential — United States, 2003–2017. MMWR 2019; 68(17);388–395

 

Metadate CD® (methyphenidate HCL) [prescribing information]. Rochester, NY: Unither Manufacturing, LLC; 2016. Accessed April 17, 2024.

 

Metadate® ER (methylphenidate HCL) [prescribing information]. Rochester, NY: Unither Manufacturing, LLC; April 2018. Accessed April 17, 2024.

 

Methylin® (methylphenidate HCL) [prescribing information]. Florham Park, NJ: Shionogi Inc.; August 2017. Accessed April 17, 2024.

 

Mydayis® (amphetamine mix salt) [prescribing information]. Lexington, MA: Shire US Inc. September 2019. Accessed April 17, 2024.

 

ProCentra® (dextroamphetamine sulfate) [prescribing information]. Charlotte, NC: FSC Laboratories, Inc; 2010. Accessed April 17, 2024.

 

Quillichew ER™ (methylphenidate) [prescribing information]. Cupertino, CA: NextWave Pharmaceuticals, Inc.; August 2018. Accessed April 17, 2024.

 

Quillivant XR® (methylphenidate) [prescribing information]. Cupertino, CA: NextWave Pharmaceuticals, Inc.; August 2018. Accessed April 17, 2024.

 

Relexxii® (methylphenidate hydrochloride extended-release tablets) [prescribing information]. Alpharetta, GA: Vertical Pharmaceuticals, LLC; November 2021. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b7677cf9-95e0-4091-ac51-8f237c3f2635. Accessed April 17, 2024.

 

Ritalin® (methylphenidate HCL) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; January 2019. Accessed April 17, 2024.

 

Ritalin LA® (methylphenidate HCL) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; November 2019. Accessed April 17, 2024.

 

Spencer et al. A Large, double-blind, randomized clinical trial of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder. Biological Psychiatry Volume 57, Issue 5, March 1, 2005, pages 456-463

 

Spencer et al. Efficacy of a mixed amphetamine salts compound in adults with ADHD. Archives general Psychiatry (2001).

 

Swanson, J. Long-acting stimulants: development and dosing. Can Child Adolesc Psychiatr Rev. 2005 Aug; 14(Suppl 1): 4-9.

 

Vyvanse® (lisdexamphetamine dimesylate) [prescribing information]. Exton, PA: Shire LLC; January 2018. Accessed April 17, 2024.

 

Xelstrym™ (dextroamphetamine) [prescribing information]. Miami, FL: Noven Pharmaceuticals; November 2022. Available from: https://www.xelstrym.com/. Accessed April 17, 2024.

 

Yanofski, J. The Dopamine-Dilemma – Part II: Could Stimulants Cause Tolerance, Dependence, and Paradoxical Decompensation? Innovations in Clinical Neuroscience, 2011.

 

Zenzedi™ (dextroamphetamine) [prescribing information]. Atlanta, GA: Arbor Pharmaceuticals, Inc.; 2017 Accessed April 17, 2024.


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​Off-Label Use Rx.01.33

Prior Authorization Requirements for Select Drugs Rx.01.202

Weight Loss Agents Rx.01.94


Brand NameGeneric Name
Adderall® [IR/XR]Amphetamine/Dextroamphetamine
Mydayis®Amphetamine/Dextroamphetamine
Adzenys® [XR ODT/ER]Amphetamine
Dyanavel® XRAmphetamine
Evekeo® [ODT]Amphetamine
Dexedrine® [IR/SA]Dextroamphetamine sulfate
ProCentra®Dextroamphetamine sulfate
Zenzedi®Dextroamphetamine
Xelstrym®Dextroamphetamine
Focalin® [IR/XR]Dexmethylphenidate HCL
Vvyanse®Lisdexamfetamine dimesylate
Adhansia XR™Methylphenidate HCL
Aptensio® XRMethylphenidate HCL
Concerta®Methylphenidate HCL
Daytrana®Methylphenidate HCL
Jornay PM™Methylphenidate HCL
Metadate® [ER/CD]Methylphenidate HCL
Methylin®Methylphenidate HCL
Ritalin® [IR/LA]Methylphenidate HCL
Quillichew® ERMethylphenidate HCL
Quillivant® XRMethylphenidate HCL
Cotempla®Methylphenidate ER
Relexxii®Methylphenidate ER
Desoxyn®Methamphetamine HCL
Azstarys™Serdexmethylphenidate/Dexmethylphenidate

stimulantsstimulants
410
  
7/1/2024Rx.01.84CommercialOyenusi, OluwadamilolaQ1-2024
Insomnia is one of the most common medical complaints, generating more than 5 million office visits per year in the United States.  Typical complaints include difficulty falling asleep, staying asleep, and variable sleep.  Insomnia is present when all of the following criteria are met:

  1. A complaint of difficulty initiating sleep, difficulty maintaining sleep, or waking up too early. In children or individuals with dementia, the sleep disturbance may manifest as resistance to going to bed at the appropriate time or difficulty in sleeping without caregiver assistance.
  2. The above sleep difficulty occurs despite adequate opportunity and circumstances for sleep.
  3. The impaired sleep produces deficits in daytime function.
Insomnia is classified as short-term, long-term, or other depending upon the duration and causes.
 
Non-24-hour sleep-wake rhythm disorder is characterized by failure of the circadian system to maintain stable alignment (called "entrainment") to the 24-hour day. As a result, the circadian system "free runs" and typically shifts to progressively later phase positions. The most common cause is blindness, as the daily light-dark cycle is the most powerful environmental cue for synchronizing the hypothalamic pacemaker to the 24-hour day.

Sleep problems are often significant in individuals diagnosed with Smith-Magenis Syndrome and include difficulty falling asleep, shortened sleep cycles, frequent and prolonged nocturnal awakening (altered rapid eye movement [REM] sleep), excessive daytime sleepiness, daytime napping, snoring, and bedwetting. Sleep problem appear to be due to an inversion of melatonin secretion. 
 Zolpidem tartrate (Ambien®) is a gamma-aminobutyric acid (GABA) A receptor positive modulator, is indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation.

Zolpidem tartrate (Ambien CR®) is a gamma-aminobutyric acid (GABA) A receptor positive modulator, is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.
  
Zolpidem tartrate (Edluar®) and (Zolpimist®) are gamma-aminobutyric acid (GABA) A receptor positive modulators indicated for the treatment of insomnia characterized by difficulties with sleep initiation.  ​

Zolpidem tartrate sublingual tablet (Intermezzo®) is a GABAA agonist indicated for use as needed for the treatment of insomnia when a middle-of-the-night awakening is followed by difficulty returning to sleep. 
 
Zolpidem tartrate sublingual tablet (Intermezzo®) is a GABAA agonist indicated for use as needed for the treatment of insomnia when a middle-of-the-night awakening is followed by difficulty returning to sleep.  

Tasimelteon (Hetlioz®/ Hetlioz LQ®oz®) is indicated for:

  1. Capsules: Treatment of non-24-Hour Sleep-Wake Disorder (Non-24) in adults and nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) in patients 16 years of age and older
  2. Oral suspension: Treatment of nighttime sleep disturbances in SMS in pediatric patients 3 years to 15 years of age
Tasimelteon (Hetlioz®/ Hetlioz LQ®) is an agonist of melatonin receptors MT1 and MT2 (greater affinity for the MT2 receptor than the MT1 receptor). Activation of MT1 is thought to preferentially induce sleepiness, while MT2 receptor activation preferentially influences regulation of circadian rhythms.

The intent of this policy is to communicate the medical necessity criteria for zolpidem tartrate (Ambien® and Ambien CR®), zolpidem (Intermezzo®, Zolpimist®), zolpidem tartrate sublingual tablets (Edluar®), eszopiclone 3mg (Lunesta®) and tasimelteon (Hetlioz®/Hetlioz LQ®) as provided under the member's prescription drug benefit.​

Insomnia
INITIAL CRITERIA: Edluar® 5mg, Zolpimist® are approved when ALL of the following are met:

  1. Diagnosis of insomnia; and
  2. Member is 18 years of age or older; and
  3. One of the following:
    1. Inadequate response or inability to tolerate TWO of the following:
      1. Eszopiclone
      2. Zaleplon
      3. Zolpidem; OR
    2. Inability to swallow capsules/tablets (i.e., dysphagia, gastrointestinal [GI] tubes)

 
INITIAL CRITERIA: Any of the following high dose products (brand and generic): zolpidem tartrate (Ambien®) 10mg, zolpidem tartrate ER (Ambien® CR) 12.5mg, eszopiclone (Lunesta®) 3mg or Edluar® 10mg is approved when ALL of the following are met:

  1. Diagnosis of insomnia; and
  2. Member is 18 years of age or older; and
  3. Patient has been counseled on practices associated with good sleep hygiene (e.g., avoiding stimulants such as caffeine, nicotine, alcohol close to bedtime, etc.); and
  4. Inadequate response to a two-week trial of the lower dose; and
  5. For brand products with generic equivalents only, inadequate response or inability to tolerate a generic equivalent


Initial authorization duration: 2 years


REAUTHORIZATION CRITERIA: Edluar® 5mg, Zolpimist®, zolpidem tartrate (Ambien®) 10mg, zolpidem tartrate ER (Ambien® CR) 12.5mg, eszopiclone (Lunesta®) 3mg, or Edluar® 10mg is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years
 
 Non-24 hour Sleep-Wake Disorder

INITIAL CRITERIA Tasimelteon (Hetlioz®) is approved when ALL of the following are met:

  1. Prescribed by or in consultation with a sleep specialist or neurologist; and
  2. Diagnosis of Non-24-hour Sleep-Wake Disorder (also known as free-running disorder, free-running or non-entrained type circadian rhythm sleep disorder, or hypernychthemeral syndrome); and
  3. Member is 18 years of age or older; and
  4. Member is totally blind (has no light perception); and
  5. Member has circadian period greater than 24 hours; and
  6. For brand Hetlioz only, inadequate response or inability to tolerate generic tasimelteon

 

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: Hetlioz® is re-approved when there is documentation of positive clinical response to therapy.
 

Reauthorization duration: 2 years 

 
Smith-Magenis Syndrome
 

INITIAL CRITERIA Tasimelteon (Hetlioz®/Hetlioz LQ®) is approved when ALL of the following are met:

  1. Prescribed by or in consultation with a sleep specialist or neurologist; and
  2. Diagnosis of Smith-Magenis Syndrome; and
  3. Member experiences nighttime sleep disturbances (i.e., difficulty falling asleep, frequent nighttime waking and early waking); and
  4. One of the following:
    1. For Hetlioz only, member is 16 years of age or older; or
    2. For Hetlioz LQ only, member is 3 to 15 years of age; and
  5. For brand Hetlioz capsules only, inadequate response or inability to tolerate generic tasimelteon

 
Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: Hetlioz®/Hetlioz LQ® is re-approved when there is documentation of positive clinical response to therapy (i.e., improvement in nighttime total sleep time, improvement in nighttime sleep quality)
 
Reauthorization duration: 2 years


Complex Sleep Behaviors: zolpidem tartrate (Ambien® and Ambien CR®), zolpidem (Intermezzo®, Zolpimist®), zolpidem tartrate sublingual tablets (Edluar®), eszopiclone 3mg (Lunesta®)

 
Complex sleep behaviors including sleepwalking, sleep driving, and engaging in other activities while not fully awake have been reported following use of zolpidem tartrate and eszopiclone. Some of these events have resulted in serious injuries, including death. Discontinue immediately if a patient experiences a complex sleep behavior. 

Allain H, Bentue-Ferrer D, Breton SL, Polard E, Gandon JM. Preference of insomniac patients between a single dose of zolpidem 10 mg versus zaleplon 10 mg. Hum Psychopharmacol. 2003;18(5):369-374.

 

Ambien® (zolpidem tartrate) [prescribing information]. Bridgewater, NJ: sanofi-aventis; February 2022. Available at https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=c36cadf4-65a4-4466-b409-c82020b42452&type=display. Accessed April 17, 2024.

 

Ambien CR® (zolpidem tartrate) [package insert]. Bridgewater, NJ: sanofi-aventis; February 2022. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=404c858c-89ac-4c9d-8a96-8702a28e6e76&type=display. Accessed April 17, 2024.

 

Ancoli-Israel S, Walsh JK, Mangano RM, Fujimori M. Zaleplon, a novel nonbenzodiazepine hypnotic, effectively treats insomnia in elderly patients without causing rebound effects. Prim Care Companion J Clin Psychiatry. 1999;1(4):114-120.

 

Bonnet MH, Arand DL. Risk factors, comorbidities, and consequences of insomnia in adults. UpToDate. August 2023. Available at: https://www.uptodate.com/contents/overview-of-insomnia?source=search_result&search=insomnia&selectedTitle=2~150. Accessed April 17, 2024.

 

Elie R, Ruther E, Farr I, Emilien G, Salinas E. Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic. Zaleplon Clinical Study Group. Clin Psychiatry. 1999;60(8):536-544.

 

Edluar® [package insert]. Somerset, NJ: Meda Pharmaceuticals, Inc.; August 2022. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a32884d0-85b5-11de-8a39-0800200c9a66&type=display. Accessed April 17, 2024.

 

Fry J, Scharf M, Mangano R, Fujimori M. Zaleplon improves sleep without producing rebound effects in outpatients with insomnia. Zaleplon Clinical Study Group. Int Clin Psychopharm. 2000;15(3):141-152.

 

Hetlioz® (tasimelteon) [prescribing information]. Vanda Pharmaceuticals, Inc.: Washington, DC.; January 2024. Available at:https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=ca4a9b63-708e-49e9-8f9b-010625443b90&type=display. Accessed April 17, 2024.

 

Intermezzo® (zolpidem tartrate) [prescribing information]. Stamford, CT: Purdue Pharma LP; November 2022. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=913b6cfe-1fb0-44a8-817a-26374bbce995&type=display. Accessed April 17, 2024.

 

Lunesta® (eszopiclone) [prescribing information]. Marlborough, MA: Sunovion Pharmaceuticals Inc. August 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fd047b2b-05a6-4d99-95cb-955f14bf329f. Accessed April 17, 2024.

 

Krystal A, Walsh JK, Laska E, et al. Sustained efficacy of eszopiclone over 6 months of nightly treatment: Results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia. Sleep. 2003;26(7):793-799.

 

Rosenberg RP. Eszopiclone, a novel non-benzodiazepine sedative-hypnotic: Efficacy and safety in a model of transient insomnia (Abstract). Sleep. 2002;25(suppl):A68.

 

Roth T, Krystal A, Walsh J, Roehrs T, Wessel T, Caron J. Twelve months of nightly eszopiclone treatment in patients with chronic insomnia: Assessment of long-term efficacy and safety (Abstract). Sleep. 2004;27(suppl):A260.

 

Goldstein C. Overview of circadian sleep-wake rhythm disorders. UpToDate. December 2023. Available at: https://www.uptodate.com/contents/overview-of-circadian-sleep-wake-rhythm-disorders?source=search_result&search=non%2024&selectedTitle=1~94. Accessed April 17, 2024.

 

Zammit GK, McNabb LJ, Caron J, Amato DA, Roth T. Efficacy and safety of eszopiclone across 6 weeks of treatment for primary insomnia. Curr Med Res Opin. 2004:20(12):1979-1991.  

 

Zolpimist® (zolpidem tartrate spray) [prescribing information]. Louisville, KY: Magna Pharmaceuticals; August 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b2e26965-30bd-4dca-869d-8a70b23b6d62&type=display. Accessed April 17, 2024.


193/14/20243/14/20257/1/2024 1:27 AMNo presence informationsrv_ppsgw_P
Off-Label Use Rx.01.33

Quantity Lvel Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit Rx.01.76

Brand NameGeneric Name
Ambien® [CR]zolpidem tartrate immediate and extended release (PA applies to generic 10mg IR and 12.5mg CR)
Edluar®zolpidem sublingual tablets
Zolpimist®zolpidem
Intermezzo®zolpidem
Lunesta®eszopiclone
Hetlioz®/Hetlioz LQ®
tasimelton

Ambien®, Ambien CR®, Intermezzo®, Zolpimist®, Edluar®, Lunesta®, Hetlioz®/Hetlioz LQ®zolpidem tartrate, zolpidem tartrate sublingual tablets, eszopiclone 3mg, tasimelteon
411
  
7/1/2024Rx.01.124CommercialOluwadamilola.Oyenusi@ibx.comQ1-2024

Narcolepsy results from the loss of the neuropeptides, orexin-A and orexin-B (also known as hypocretin-1 and hypocretin-2), which have excitatory effects on the ox1 and ox2 receptors on postsynaptic neurons.  Narcolepsy is a clinical syndrome of daytime sleepiness with cataplexy, hypnagogic hallucinations, and sleep paralysis. It is the second most common cause of disabling daytime sleepiness after obstructive sleep apnea.  Typical age of onset of narcolepsy is teens to twenties. Patients with type 1 narcolepsy (narcolepsy with cataplexy) typically present with moderate to severe daytime sleepiness, transient facial weakness or falls triggered by joking or laughter (partial or complete cataplexy), or the inability to move for one or two minutes immediately after awakening or just before falling asleep. Patients with type 2 narcolepsy do not have cataplexy.

Sodium oxybate, a CNS depressant, is the sodium salt of gamma hydroxybutyrate, a metabolite of GABA.  It is hypothesized that the therapeutic effects of Xyrem® on cataplexy and excessive daytime sleepiness are mediated through GABA-B actions at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons.  The exact mechanism of sodium oxybate in narcolepsy is unknown.

Xywav™ is a CNS depressant. The exact mechanism of action in the treatment of narcolepsy is unknown. Xywav™ is a mixture of calcium oxybate, magnesium oxybate, potassium oxybate, and sodium oxybate (gamma-hydroxybutyrate). Gamma-hydroxybutyrate (GHB) is an endogenous compound and metabolite of the neurotransmitter GABA. It is hypothesized that the therapeutic effects of Xywav™ on cataplexy and excessive daytime sleepiness are mediated through GABA-B actions during sleep at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons. The active moiety of oxybate salts is the same as that of sodium oxybate (Xyrem®), and dosing is the same; the only difference is that oxybate salts (Xywav™) have 90 percent less sodium.

Sodium oxybate solution (Xyrem®) is indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy.

Sodium oxybate extended-release oral suspension (Lumryz™) is indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsy.

Calcium, magnesium, potassium and sodium oxybates (Xywav™) is indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy and idiopathic hypersomnia (IH) in adults.


The intent of this policy is to communicate the medical necessity criteria for sodium oxybate (Xyrem®/Lumryz™) and calcium, magnesium, potassium and sodium oxybates (Xywav™) as provided under the member's prescription drug benefit.

Cataplexy with narcolepsy (Type 1)
INITIAL CRITERIA: Sodium oxybate (Xyrem®) solution or calcium, magnesium, potassium and sodium oxybates (Xywav™) is approved when ALL of the following are met:

  1. Diagnosis of Cataplexy with narcolepsy (Type 1); and
  2. Member is 7 years of age or older; and
  3. Diagnosis was confirmed by ONE of the following tests:
  4. Polysomnography (PSG); or
  5. Multiple sleep latency test (MSLT); and
  6. Prescribed by or in consultation with a neurologist, psychiatrist, or sleep specialist; and
  7. No concurrent use of sedative hypnotics and alcohol; and
  8. Symptoms of cataplexy are present; and
  9. Symptoms of excessive daytime sleepiness (e.g., irrepressible need to sleep or daytime lapses into sleep) are present; and
  10. For  Xyrem® solution only, inadequate response or inability to tolerate sodium oxybate solution (by Hikma) 

Initial authorization duration: 12 months

REAUTHORIZATION CRITERIA: Sodium oxybate (Xyrem®) solution or calcium, magnesium, potassium and sodium oxybate (Xywav™) is re-approved when ALL of the following are met:

  1. Documentation to support the efficacy associated with the current regimen (including but not limited to reduction in the frequency of cataplexy attacks or an improvement in the Epworth sleepiness scale); and
  2. There is no claim history of a sedative hypnotic agents within one year of the request; and
  3. For Xyrem® solution only, inadequate response or inability to tolerate sodium oxybate solution (by Hikma); and
  4. Yearly evaluation by a neurologist, psychiatrist, or sleep specialist


    Reauthorization duration: 12 months 

    INITIAL CRITERIA: Sodium oxybate suspension extended-release (Lumryz™) is approved when ALL of the following are met:

    1. Diagnosis of Cataplexy with narcolepsy (Type 1); and
    2. Member is 18 years of age or older; and
    3. Diagnosis was confirmed by ONE of the following tests:
      1. Polysomnography (PSG); or
      2. Multiple sleep latency test (MSLT); and
    4. Prescribed by or in consultation with a neurologist, psychiatrist, or sleep specialist; and
    5. Symptoms of cataplexy are present; and
    6. Symptoms of excessive daytime sleepiness (e.g., irrepressible need to sleep or daytime lapses into sleep) are present; and
    7. No concurrent use of sedative hypnotics and alcohol

    Initial authorization duration: 12 months

    REAUTHORIZATION CRITERIA: Sodium oxybate suspension extended-release (Lumryz™) is re-approved when ALL of the following are met:

    1. Documentation to support the efficacy associated with the current regimen (including but not limited to reduction in the frequency of cataplexy attacks or an improvement in the Epworth sleepiness scale); and
    2. There is no claim history of a sedative hypnotic agents within one year of the request; and
    3. Yearly evaluation by a neurologist, psychiatrist, or sleep specialist

    Reauthorization duration: 12 month

    _____________________________________________________________________________________________________

     
    Excessive daytime sleepiness in narcolepsy (Type 2)
    INITIAL CRITERIA: Sodium oxybate (Xyrem®) solution or calcium, magnesium, potassium and sodium oxybates (Xywav™) is approved when ALL of the following are met:

    1. Diagnosis of Excessive daytime sleepiness in narcolepsy (Type 2); and
    2. Member is 7 years of age or older; and
    3. Diagnosis was confirmed by ONE of the following tests:
      1. Polysomnography (PSG); or
      2. Multiple sleep latency test (MSLT); and
    4. Inadequate response or inability to tolerate ALL of the following:
      1. Modafinil or armodafinil; and
      2. One of the following:
        1. One stimulant product (e.g., amphetamine, methylphenidate); or
        2. History of or potential for a substance use disorder; and
      3. Sunosi®; and
    5. Prescribed by or in consultation with a neurologist, psychiatrist, or sleep specialist; and
    6. No concurrent use of sedative hypnotics and alcohol; and
    7. Symptoms of cataplexy are absent; and
    8. Symptoms of excessive daytime sleepiness (e.g., irrepressible need to sleep or daytime lapses into sleep) are present; and
    9. For Xyrem® solution only, inadequate response or inability to tolerate sodium oxybate solution (by Hikma) 

    Initial authorization duration: 12 months

    REAUTHORIZATION CRITERIA: Sodium oxybate (Xyrem®) solution or calcium, magnesium, potassium and sodium oxybates (Xywav™) is re-approved when ALL of the following are met:

    1. Documentation to support the efficacy associated with the current regimen (including but not limited to reduction in the frequency of cataplexy attacks or an improvement in the Epworth sleepiness scale); and
    2. There is no claim history of a sedative hypnotic agents within one year of the request; and
    3. For Xyrem® solution only, inadequate response or inability to tolerate sodium oxybate solution (by Hikma); and
    4. Yearly evaluation by a neurologist, psychiatrist, or sleep specialist

    Reauthorization duration: 12 months 

    INITIAL CRITERIA: Sodium oxybate suspension extended-release (Lumryz™) is approved when ALL of the following are met:

    1. Diagnosis of Excessive daytime sleepiness in narcolepsy (Type 2); and
    2. Member is 18 years of age or older; and
    3. Diagnosis was confirmed by ONE of the following tests:
      1. Polysomnography (PSG); or
      2. Multiple sleep latency test (MSLT); and
    4. Inadequate response or inability to tolerate ALL of the following:
      1. Modafinil or armodafinil; and
      2. One of the following:
        1. One stimulant product (e.g., amphetamine, methylphenidate); or
        2. history of or potential for a substance use disorder; and
      3. Sunosi®; and
    5. Prescribed by or in consultation with a neurologist, psychiatrist, or sleep specialist; and
    6. Symptoms of cataplexy are absent; and
    7. Symptoms of excessive daytime sleepiness (e.g., irrepressible need to sleep or daytime lapses into sleep) are present; and
    8. No concurrent use of sedative hypnotics and alcohol

    Initial authorization duration: 12 months


    REAUTHORIZATION CRITERIA: Sodium oxybate suspension extended-release (Lumryz™) is re-approved when ALL of the following are met:

    1. Documentation to support the efficacy associated with the current regimen (including but not limited to reduction in the frequency of cataplexy attacks or an improvement in the Epworth sleepiness scale); and
    2. There is no claim history of a sedative hypnotic agents within one year of the request; and
    3. Yearly evaluation by a neurologist, psychiatrist, or sleep specialist

      Reauthorization duration: 12 months
      ______________________________________________________________________________________________

      Idiopathic Hypersomnia (IH)
      INITIAL CRITERIA: Calcium, magnesium, potassium and sodium oxybates (Xywav™) is approved when ALL of the following are met:

      1. Diagnosis of idiopathic hypersomnia; and
      2. Member is 18 years of age or older; and
      3. Diagnosis was confirmed by ONE of the following tests:
        1. Polysomnography (PSG); or
        2. Multiple sleep latency test (MSLT); and
      4. Symptoms of excessive daytime sleepiness (e.g., nap duration of longer than 60 minutes) are present; and
      5. Prescribed by or in consultation with a neurologist, psychiatrist, or sleep specialist; and
      6. No concurrent use of sedative hypnotics and alcohol


      Initial authorization duration: 12 months

      REAUTHORIZATION CRITERIA: Calcium, magnesium, potassium and sodium oxybates (Xywav™) is re-approved when ALL of the following are met:

      1. Documentation demonstrating a reduction in symptoms of excessive daytime sleepiness associated with therapy; and
      2. There is no claim history of a sedative hypnotic agents within one year of the request; and
      3. Yearly evaluation by a neurologist, psychiatrist, or sleep specialist

      Reauthorization duration: 12 months 


      WARNING: CENTRAL NERVOUS SYSTEM (CNS) DEPRESSION and ABUSE AND MISUSE.

      Central Nervous System Depression

      Xyrem®/Xywav™/Lumryz™ is a CNS depressant. In clinical trials at recommended doses, obtundation and clinically significant respiratory depression occurred in adult patients treated with Xyrem®/Xywav™/Lumryz™. Many patients who received Xyrem®/Xywav™/Lumryz™ during clinical trials in narcolepsy were receiving central nervous system stimulants. 

      Abuse and Misuse

      Xyrem®/Xywav™/Lumryz™ is the sodium salt of gamma-hydroxybutyrate (GHB). Abuse or misuse of illicit GHB is associated with CNS adverse reactions, including seizure, respiratory depression, decreased consciousness, coma, and death.

      Because of the risks of CNS depression and abuse and misuse, Xyrem®/Xywav™/Lumryz™ is available only through a restricted program called the Xyrem®/Xywav™/Lumryz™ REMS Program


      Scammel TE. Treatment of narcolepsy in adults. UpToDate. May 2023. Available at: https://www.uptodate.com/contents/treatment-of-narcolepsy-in-adults?source=search_result&search=modafinil%20narcolepsy&selectedTitle=1~143#H1. Accessed April 17, 2024.

      Lumryz™ (sodium oxybate) [package insert]. Chesterfield, MO: Avadel CNS Pharmaceuticals, LLC. May 2023. Available from: https://www.avadel.com/lumryz-prescribing-information.pdf. Accessed November 20, 2023.

      Xyrem® (sodium oxybate) [package insert]. Palo Alto, CA. Jazz Pharmaceuticals. April 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=926eb076-a4a8-45e4-91ef-411f0aa4f3ca&type=display. Accessed November 20, 2023.

      Xywav™ (calcium, magnesium, potassium, and sodium oxybates) [prescribing information]. Palo Alto, CA. Jazz Pharmaceuticals. April 2023. Available from: https://pp.jazzpharma.com/pi/xywav.en.USPI.pdf. Accessed November 20, 2023.

      Scammell TE. Clinical features and diagnosis of narcolepsy in adults. UpToDate website. Last updated July 2022. Available at http://www.uptodate.com/. Accessed November 20, 2023. 


      		163/14/20243/14/20259/21/2024 9:12 AMNo presence informationsrv_ppsgw_P
      Off-labe use Rx.01.33 

      Quantity Level Limits Covered for Pharmaceuticals Covered Under the Prescription Drug Benefit Rx.01.76

      Drug name Generic name
      Xyrem®sodium oxybate solution
      Xywav™calcium, magnesium, potassium and sodium oxybates
      Lumryz™sodium oxybate extended-release oral suspension

      		Xyrem®, Lumryz™, Xywav™ Sodium oxybate/calcium, magnesium, potassium, sodium oxybates
      412
        
      		7/1/2024Rx.01.273CommercialOyenusi, OluwadamilolaQ1-2024
      Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that causes muscle weakness, disability, and eventually death, with a median survival of three to five years. Incidence rates for ALS in Europe and North America range between 1.5 and 4.7 per 100,000 person-years, while prevalence rates range between 2.7 and 7.4 per 100,000 person-years. The loss of motor neurons results in the primary clinical symptoms and signs of ALS.

      Sodium phenylbutyrate is a histone deacetylase inhibitor that reduces an adaptive stress response in the endoplasmic reticulum. Taurursodiol (also known as ursodoxicoltaurine) appears to increase the threshold of cellular apoptosis by maintaining mitochondrial integrity through reduced membrane permeability. A coformulation of both agents, sodium phenylbutyrate-taurursodiol (PB-TURSO), is used to reduce neuronal cell death.

      Relyvrio™ is indicated for the treatment of amyotrophic lateral sclerosis (ALS) in adults.


      The intent of this policy is to communicate the medical necessity criteria for Sodium phenylbutyrate and Taurursodiol (Relyvrio™) as provided under the member's prescription drug benefit.

      INITIAL CRITERIA Sodium phenylbutyrate and taurursodiol (Relyvrio™) is approved when ALL of the following are met:

      1. Diagnosis of amyotrophic lateral sclerosis (ALS); and
      2. Diagnosis of ALS is further supported by neurogenic changes in electromyography (EMG); and
      3. Baseline functional ability has been conducted prior to initiating treatment (e.g., speech, walking, climbing stairs, etc.); and
      4. Other differential diagnoses (e.g., multifocal motor neuropathy, cervical radiculomyelopathy, inflammatory myopathies, spinobulbar muscular atrophy, myasthenia gravis, etc.) have been ruled out); and
      5. Member has a percent (%) forced vital capacity (%FVC) or slow vital capacity (%SVC) greater than or equal to 60% at the start of treatment; and
      6. Member does not require permanent noninvasive ventilation or invasive ventilation; and
      7. Member has had ALS symptoms for less than or equal to 18 months; and
      8. Member is 18 years of age or older; and
      9. Prescribed by or in consultation with a neurologist with expertise in the diagnosis of ALS

       
      Initial authorization duration: 6 months

      REAUTHORIZATION CRITERIA Sodium phenylbutyrate and taurursodiol (Relyvrio™) is re-approved when BOTH of the following are met:

      1. Documentation of slowed disease progression from baseline; and
      2. Prescribed by or in consultation with a neurologist with expertise in the diagnosis of ALS


      Reauthorization duration: 6 months


      N/A
      Maragakis NJ. Epidemiology and pathogenesis of amyotrophic lateral sclerosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 11, 2024.

      Goyal NA. Disease-modifying treatment of amyotrophic lateral sclerosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 11, 2024.

      Relyvrio™ (sodium phenylbutyrate and taurursodiol) [package insert]. Cambridge, MA: Amylyx Pharmaceuticals, Inc; September 2022. Available at https://www.relyvrio.com/RELYVRIO-US-Prescribing-Information.pdf. Accessed April 11, 2024.

      		33/14/20243/14/20257/1/2024 1:28 AMNo presence informationsrv_ppsgw_P
      Rx.01.33 Off Label Use​
      Brand NameGeneric Name
      Relyvrio™Sodium phenylbutyrate and Taurursodiol


      		Relyvrio™Sodium phenylbutyrate and Taurursodiol
      413
        
      		7/1/2024Rx.01.277CommercialOyenusi, OluwadamilolaQ1-2024
      Proteinuria, also called albuminuria, is elevated protein in the urine. It is not a disease in and of itself but a symptom of certain conditions affecting the kidneys. Typically, too much protein in the urine means that the kidneys’ filters — the glomeruli — are not working properly and are allowing too much protein to escape in the urine. IgA nephropathy is an autoimmune disease resulting from dysregulation of mucosal-type IgA immune responses.

      Sparsentan is a single molecule with antagonism of the endothelin type A receptor (ETAR) and the angiotensin II type 1 receptor (AT1R). Sparsentan has high affinity for both the ETAR (Ki= 12.8 nM) and the AT1R (Ki=0.36 nM), and greater than 500-fold selectivity for these receptors over the endothelin type B and angiotensin II subtype 2 receptors. Endothelin-1 and angiotensin II are thought to contribute to the pathogenesis of IgAN via the ETA R and AT1R, respectively.

      Filspari™ is indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g.

      ​The intent of this policy is to communicate the medical necessity criteria for Sparsentan (Filspari™) as provided under the member's prescription drug benefit. 

      INITIAL CRITERIA: Sparsentan (Filspari) is approved when all of the following are met:

      1. Diagnosis of primary immunoglobulin A nephropathy (IgAN) as confirmed by a kidney biopsy; and
      2. Documentation is provided that member is at risk of rapid disease progression [e.g., generally a urine protein-to-creatinine ratio (UPCR) greater than or equal to 1.5 g/g, or by other criteria such as clinical risk scoring using the International IgAN Prediction tool]; and
      3. Medication will be used to reduce proteinuria; and
      4. Member has an estimated glomerular filtration rate (eGFR) of greater than or equal to 30 mL/min/1.73m2; and
      5. Member had an inadequate response or inability to tolerate a minimum 90-day trial of a maximally tolerated dose of one of the following:
        1. Angiotensin-receptor blockers (ARB) (e.g., losartan, valsartan); or
        2. Angiotensin-converting enzyme (ACE) inhibitor (e.g., benazepril, lisinopril); and
      6. Medication will not be used in combination with any of the following:
        1. Angiotensin receptor blockers
        2. Endothelin receptor antagonists (ERAs) (e.g., ambrisentan, bosentan, Opsumit)
        3. Aliskiren; and
      7. Member is 18 years or age or older; and
      8. Prescribed by or in consultation with a nephrologist

       Initial authorization duration: 1 year

      CONTINUATION CRITERIA: Sparsentan (Filspari) is approved when BOTH of the following are met:

      1. Documentation of positive clinical response to therapy from baseline as demonstrated by a decrease in urine protein-to-creatinine ratio (UPCR); and
      2. Prescribed by or in consultation with a nephrologist; and
      3. Medication is not taken in combination with any of the following:
        1. Angiotensin receptor blocker or angiotensin receptor-neprilysin inhibitor
        2. Endothelin receptor antagonists (ERAs) (e.g, ambrisentan, bosentan, Opsumit)
        3. Aliskiren

      Continuation authorization duration: 1 year


      WARNING: HEPATOTOXICITY and EMBRYO-FETAL TOXICITY

      FILSPARI is only available through a restricted distribution program called the FILSPARI Risk Evaluation and Mitigation Strategies (REMS) because of these risks. Some endothelin receptor antagonists have caused elevations of aminotransferases, hepatotoxicity, and liver failure. Measure liver aminotransferases and total bilirubin prior to initiation of treatment and ALT and AST monthly for 12 months, then every 3 months during treatment. Interrupt treatment and closely monitor patients developing aminotransferase elevations more than 3x Upper Limit of Normal (ULN). Based on animal data, FILSPARI can cause major birth defects if used during pregnancy. Pregnancy testing is required before, during, and after treatment. Patients who can become pregnant must use effective contraception prior to initiation of treatment, during treatment, and for one month after.



      Filspari™ (sparsentan) [package insert]. San Diego, CA: Travere Therapeutics, Inc. February 2023. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf. Accessed April 16, 2024.

      Cattran DC. IgA nephropathy: Treatment and prognosis. UpToDate. March 2024. Available at: https://www.uptodate.com. Accessed April 16, 2024.

      “Proteinuria." JHM, 19 Nov. 2019, www.hopkinsmedicine.org/health/conditions-and-diseases/proteinuria.

      		23/14/20243/14/20257/1/2024 1:28 AMNo presence informationsrv_ppsgw_P
      ​Rx.01.33 Off Label Use
      Brand NameGeneric Name
      Filspari™Sparsentan

      		Filspari™Sparsentan
      420
        
      		7/1/2024Rx.01.161CommercialOyenusi, OluwadamilolaQ1-2024

      Gaucher disease is a lysosomal storage disorder and results from not having enough glucocerebrosidase (GCase), an important enzyme that breaks down a fatty chemical called glucocerebroside. Because the body cannot break down this chemical, fat-laden Gaucher cells build up in areas like the spleen, liver and bone marrow.

      Type 1 Gaucher disease is caused by a functional deficiency of GCase, the enzyme that mediates the degradation of the glycosphingolipid glucosylceramide. The failure to degrade glucosylceramide results in the lysosomal storage of this material within tissue macrophages leading to widespread pathology. Macrophages containing stored glucosylceramide are typically found in the liver, spleen, and bone marrow and occasionally in lung, kidney, and intestine. Secondary hematologic consequences include severe anemia and thrombocytopenia in addition to the characteristic progressive hepatosplenomegaly. Skeletal complications include osteonecrosis and osteopenia with secondary pathological fractures. 

      Type 1 Gaucher disease is the most common form of the disease in western countries, making up roughly 95 percent of patients there. Symptoms include spleen and liver enlargement, bone problems and fatigue. Brain development is normal.

      Treatment of Gaucher disease consists of therapy with one of two mechanisms: enzyme replacement therapy (ERT) or substrate reduction therapy (SRT). ERT, the current standard of care balances low levels of GCase allowing glucosylceramide to be broken down. The three ERT regimens currently available are imiglucerase (Cerzyme), velaglucerase alfa (Vpriv), and taliglucerase alfa (Elelyso). SRT works by blocking the enzyme that is responsible for synthesizing glucosylceramide. Two SRT therapies, miglustat (Zavesca) and eliglustat (Cerdelga), are available.

      Miglustat and eliglustat inhibit glucosylceramide synthase, reducing the accumulation of glucosylceramide in macrophages.  In clinical trials, miglustat and eliglustat improved liver and spleen volume, as well as hemoglobin concentration and platelet count.

      Miglustat (Zavesca®, Yargesa) is indicated for the treatment of adult patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option (e.g., because of allergy, hypersensitivity, or poor venous access).

      Eliglustat (Cerdelga®) is indicated for long-term treatment of adult patients with Gaucher disease type 1 (GD1) who are cytochrome P450 2D6 (CYP2D6) extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) as detected by an FDA-cleared test.  CYP2D6 ultra-rapid metabolizers may not achieve adequate concentrations of CERDELGA to achieve a therapeutic effect. A specific dosage cannot be recommended for CYP2D6 indeterminate metabolizers.


      The intent of this policy is to communicate the medical necessity criteria for miglustat (Zavesca®, Yargesa) and eliglustat (Cerdelga®) as provided under the member's prescription drug benefit.

      ​

      Type 1 Gaucher Disease

      INITIAL CRITERIA: Miglustat (Zavesca®, Yargesa) is approved when ALL of the following are met:

      1. Member is 18 years of age or older; and
      2. Diagnosis of mild to moderate type 1 Gaucher disease; and
      3. Prescribed as monotherapy for members in whom enzyme replacement therapy is not a therapeutic option (e.g., allergy, hypersensitivity, or poor venous access).

       

      Initial authorization duration: 12 months

      REAUTHORIZATION CRITERIA: Miglustat (Zavesca®, Yargesa) is re-approved when there is documentation of positive clinical response to therapy.

      Reauthorization duration: 2 years

      INITIAL CRITERIA: Eliglustat (Cerdelga®) is approved when ALL of the following are met:

      1. Member is 18 years of age or older; and
      2. Diagnosis of Type 1 Gaucher disease; and
      3. Member is CYP2D6 extensive metabolizer (EM), intermediate metabolizer (IM), or poor metabolizer (PM) as detected by an FDA-cleared test for determining CYP2D6 genotype [not indicated for Ultra Rapid Metabolizers (URM) as they may not achieve adequate concentration of eliglustat to achieve a therapeutic effect]

       

      Initial authorization duration: 12 months

      REAUTHORIZATION CRITERIA: Eliglustat (Cerdelga®) is re-approved when there is documentation of positive clinical response to therapy (i.e. hemoglobin level decrease by greater than 1.5g/dL from baseline, platelet count decrease by greater than 25% from baseline, spleen volume increased by greater than 25% from baseline, liver volume increased by greater than 20% from baseline).

      Reauthorization duration: 2 years


      None

      Bennett LL, Mohan D.  Gaucher Disease and its treatment options. Ann Pharmacother. 2013 Sep;47(9):1182-93. Doi: 10.1177/1060028013500469.

      Cerdelga® (eliglustat) [prescribing information]. Waterford, Ireland. Genzyme Corporation, A Sanofi Company. December 2022. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=819f828a-b888-4e46-83fc-94d774a28a83&type=display. Accessed April 17, 2024.

      Cox TM, Drelichman G, Cravo R, et al.  ENCORE: A multi-national, randomized, controlled, open-label, non-inferiority study comparing eliglustat with imiglucerase in Gaucher Disease type 1 patients on enzyme replacement therapy who have reached therapeutic goals. Poster presented at: Lysosomal Disease Network 10th Annual World Symposium; February 11-13, 2014; San Diego, CA. 

      Eliglustat. Micromedex Solutions. Available at www.micromedexsolutions.com. Accessed April 17, 2024.

      Miglustat. Micromedex Solutions. Available at www.micromedexsolutions.com. Accessed April 17, 2024.

      National Gaucher Foundation, Inc. Position statement for treatment of gaucher disease. January 7, 2014. Available at: http://www.gaucherdisease.org/ngf-position-statement.php. Accessed April 17, 2024. 

      National Organization for Rare Disease – Gaucher Disease. March 3, 2014. Available at: https://rarediseases.org/rare-diseases/gaucher-disease/.  Accessed April 17, 2024.

      Ross L, Peterschmitt MJ, Puga AC. Eliglustat adverse event data from a pooled analysis of four trials in Gaucher Disease type 1. Poster presented at: Lysosomal Disease Network 10th Annual World Symposium; February 11-13, 2014; San Diego, CA.

      Shankar S, Lukina E, Amato D, et al. ENGAGE: A phase 3, randomized, double blind, placebo controlled study of the efficacy and safety of eliglustat in adults with Gaucher Disease type 1: 9 month results. Poster presented at: 55th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2013; New Orleans, LA. 

      Yargesa (miglustat) [package insert]. Parsippany, NJ: Edenbridge Pharmaceuticals, LLC. October 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2b371dfe-e2b0-47fe-b677-a7bde7149f87. Accessed April 17, 2024.

      Zavesca® (miglustat) [prescribing information]. San Francisco, CA. Actelion Pharmaceuticals US, Inc. August 2022. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=817892d1-ee12-4632-85fc-57ccdf16d7b8&type=display#section-10.1. Accessed April 17, 2024. 


      		163/14/202412/18/20247/1/2024 1:29 AMNo presence informationsrv_ppsgw_P
      Rx.01.33 Off Label Use Policy 
      Brand NameGeneric Name
      Zavesca®, Yargesa
      		miglustat
      Cerdelga®eliglustat

      		NANA
      425
        
      		7/1/2024Rx.01.289CommercialOyenusi, OluwadamilolaQ1-2024
      In the United States, it is estimated that 2.7 to 3.9 million people are chronically infected with HCV. Chronic HCV infection occurs after acute infection with the virus. It is estimated that approximately 75%-85% of acute infections become chronic. The remaining 15%-25% clear the virus without treatment and do not develop chronic HCV. Genotype (GT) 1 is the most prevalent, with the breakdown as follows: GT 1a: 46.2%, GT1b: 26.3%, GT2: 10.7%, GT3: 8.9%, GT4: 6.3%, GT6: 1.1%, mixed GT/ other: 0.5%. 

      The goal of treating chronic HCV is to "reduce all-cause mortality and liver-related health adverse consequences, including end-stage liver disease and hepatocellular carcinoma, by the achievement of virologic cure as evidenced by a sustained virologic response (SVR)." SVR is defined as the "continued absence of detectable HCV RNA at least 12 weeks after completion of therapy" and is considered a marker for cure of HCV. Several benefits are associated with HCV cure, including decreases in liver inflammation, progression to liver fibrosis, hepatocellular carcinoma, liver-related mortality and liver transplantation. 

      Chronic hepatitis B describes a spectrum of disease usually characterized by the presence of detectable hepatitis B surface antigen in the blood or serum for longer than 6 months. In some individuals, chronic hepatitis B is inactive and does not present significant health problems, but others may progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The goal of treatment for chronic hepatitis B is to prevent cirrhosis, HCC and liver failure.

      Pegylated recombinant human interferon alfa-2a is an inducer of the innate antiviral immune response.

      PEGASYS is an inducer of the innate immune response indicated for the treatment of: 
      Chronic Hepatitis C (CHC)
      Adult Patients: In combination therapy with other hepatitis C virus drugs for adults with compensated liver disease. PEGASYS monotherapy is indicated only if patient has contraindication or significant intolerance to other HCV drugs. 
      Pediatric Patients: In combination with ribavirin for pediatric patients 5 years of age and older with compensated liver disease 

      Chronic Hepatitis B (CHB) 
      Adult Patients: Treatment of adults with HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB) infection who have compensated liver disease and evidence of viral replication and liver inflammation 
      Pediatric Patients: Treatment of non-cirrhotic pediatric patients 3 years of age and older with HBeAg-positive CHB and evidence of viral replication and elevations in serum alanine aminotransferase (ALT)


      The intent of this policy is to communicate the medical necessity criteria for peginterferon alfa-2a (Pegasys) as provided under the member's prescription drug benefit. 

      Chronic Hepatitis C (CHC)

      INITIAL CRITERIA: Peginterferon alfa-2a (Pegasys®) is approved when ALL of the following are met:

      1. Diagnosis of Chronic Hepatis C (CHC); and
      2. Member is without decompensated liver disease (defined as Child-Pugh Class B or C); and
      3. One of the following:
        1. Used in combination with one of the following:
          1. Sovaldi (sofosbuvir); or
          2. Ribavirin; or
        2. Inadequate response or inability to tolerate all other HCV agents (e.g., Sovaldi (sofosbuvir), ribavirin); and
      4. Prescribed by or in consultation with one of the following:
        1. Hepatologist
        2. Gastroenterologist
        3. Infectious disease specialist
        4. HIV specialist certified through the American Academy of HIV medicine

       
      Initial authorization duration: 28 weeks

      REAUTHORIZATION CRITERIA: Peginterferon alfa-2a (Pegasys®) is re-approved when ALL of the following are met:

      1. Member has an undetectable HCV RNA at week 24; and
      2. Additional treatment weeks of peginterferon are required to complete treatment regimen; and
      3. Member has not exceeded 48 weeks of therapy with peginterferon; and
      4. Prescribed by or in consultation with one of the following:
        1. Hepatologist
        2. Gastroenterologist
        3. Infection disease specialist
        4. HIV specialist certified through the American Academy of HIV medicine

       
      Reauthorization duration: 20 weeks

      _______________________________________________________________________________________________
       
      Chronic Hepatitis B (CHB)
       
      Peginterferon alfa-2a (Pegasys®) is approved when BOTH of the following are met:

      1. Diagnosis of chronic hepatitis B infection; and
      2. Member is without decompensated liver disease (defined as Child-Pugh Class B or C)

       
      Authorization duration: 48 weeks


      WARNING: RISK OF SERIOUS DISORDERS 
      See full prescribing information for complete boxed warning. 
      Risk of Serious Disorders  May cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Monitor closely and withdraw therapy with persistently severe or worsening signs or symptoms of the above disorders
      American Association for the Study of Liver Disease, Infectious Diseases Society or America, International Antiviral Society-USA. Recommendations for testing, managing and treating Hepatitis C. Available from https://www.hcvguidelines.org/.  Accessed April 17, 2024. 

      Hepatitis B (chronic): diagnosis and management. London: National Institute for Health and Care Excellence (NICE); 2017 Oct. (NICE Clinical Guidelines, No. 165.)       Available from: https://www.ncbi.nlm.nih.gov/books/NBK553697/. Accessed April 17, 2024. 

      Pegasys (peginterferon alfa-2a) [package insert]. South San Francisco, CA: Genetech USA, Inc. March 2023. Available at: PEGASYS Prescribing Information (gene.com). Accessed April 17, 2024. 
      		13/14/20243/14/20257/1/2024 1:30 AMNo presence informationsrv_ppsgw_P
      Rx.01.33​ Off-label Use 
      Brand NameGeneric Name
      Pegasyspeginterferon alfa-2a

      		Pegasys®Peginterferon alfa-2a
      426
        
      		7/1/2024Rx.01.290CommercialOyenusi, OluwadamilolaQ1-2024
      Infantile hemangioma is a common benign vascular tumors in infancy and present in up to 5% of children. In most cases, infantile hemangioma is not visibile after birth or is only present as a faint discoloration with a light halo and become evident in a period of one to two weeks after birth. Most of the infantile hemangioma presents in the face and neck region. In the case of deeply localized infantile hemangiomas presenting as bluish tumors without clear borders, the diagnosis may be delayed until up to 3 months after birth. The natural cycle of infantile hemangioma consists of three phases: the rapid proliferation phase (with the fastest growth between 5.5 and 7.5 weeks), the plateau phase, and the slow involution phase. The maximum size is achieved at around 9 months on average, and regression is completed by the age of 4 years in 90% of cases. The possible complications of infantile hemangiomas include ulceration, disfigurement, obstruction, and functional impairment. Most hemangiomas do not require immediate treatment due to their self-involuting pattern of growth; therefore, “active observation” is recommended. However, about 10% of cases are referred to as high-risk hemangiomas  because of their size, character, or location and are in need of immediate intervention.

      HEMANGEOL oral solution is a beta-adrenergic blocker indicated for the treatment of proliferating infantile hemangioma requiring systemic therapy. The mechanism of HEMANGEOL’s effects on infantile hemangiomas is not well understood.

      The intent of this policy is to communicate the medical necessity criteria for propranolol (Hemangeol) oral solution as provided under the member's prescription drug benefit. 

      Propranolol oral solution (Hemangeol™) is approved when all of the following are met:

      1. Diagnosis of proliferating infantile hemangioma; and
      2. Member is less than 1 year of age.

       

      Authorization Duration: through member's age of 12 months


      None

      Hemangeol (propranolol hydrochloride oral solution) [package insert]. Parsippany, NJ: Pierre Fabre Pharmaceuticals, Inc. June 2021. Available: https://hemangeol.com/wp-content/uploads/2023/01/Prescribing-Information-Hemangeol.pdf. Accessed April 17, 2024.

      Léauté-Labrèze C., Harper J.I., Hoeger P.H. Infantile haemangioma. Lancet. 2017;390:85–94. doi: 10.1016/S0140-6736(16)00645-0. Accessed April 17, 2024.  

      Léauté-Labrèze C., De La Roque E.D., Hubiche T., Boralevi F., Thambo J.-B., Taïeb A. Propranolol for Severe Hemangiomas of Infancy. N. Engl. J. Med. 2008;358:2649–2651. doi: 10.1056/NEJMc0708819. Accessed April 17, 2024.  


      		13/14/20243/14/20257/1/2024 1:30 AMNo presence informationsrv_ppsgw_P
      Rx.01.33 Off-Label Use 
      Brand NameGeneric Name
      HemangeolPropranolol hydrochloride

      		Hemangeol™Propranolol oral solution
      428
        
      		7/1/2024Rx.01.260CommercialOyenusi, OluwadamilolaQ1-2024
      Achondroplasia is the most common bone dysplasia in humans, with a prevalence of approximately 1 in 20,000 live births. It is an autosomal dominant condition caused by pathogenic variants in the fibroblast growth factor receptor 3 (FGFR3) gene. The most salient clinical features include disproportionate short stature (adult height is approximately 4 feet), long-bone shortening that predominantly affects the proximal aspects of the upper and lower extremities (rhizomelic shortening), and macrocephaly. Patients with achondroplasia may have delayed motor development early on, but cognition is normal. Use of growth hormone is not recommended and can potentially worsen the disproportion seen in these patients.

      Vosoritide (Voxzogo™) is indicated to increase linear growth in pediatric patients with achondroplasia with open epiphyses

      In patients with achondroplasia, endochondral bone growth is negatively regulated due to a gain of function mutation in fibroblast growth factor receptor 3 (FGFR3). Binding of vosoritide to natriuretic peptide receptor-B (NPR-B) antagonizes FGFR3 downstream signaling by inhibiting the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the mitogen-activated protein kinase (MAPK) pathway at the level of rapidly accelerating fibrosarcoma serine/threonine protein kinase (RAF-1). As a result, vosoritide, like CNP, acts as a positive regulator of endochondral bone growth as it promotes chondrocyte proliferation and differentiation.



      The intent of this policy is to communicate the medicalnecessity criteria for Vosoritide (Voxzogo™­) as provided under the member's prescription drug benefit.



      ​

      INITIAL CRITERIA Vosoritide (Voxzogo™) is approved when ALL of the following are met:

      1. Diagnosis of achondroplasia as confirmed by ONE of the following:
        1. BOTH of the following:
          1. Member has clinical manifestations characteristic of achondroplasia (e.g., macrocephaly, frontal bossing, midface retrusion, disproportionate short stature with rhizomelic shortening of the arms and the legs, brachydactyly, trident configuration of the hands, thoracolumbar kyphosis, and accentuated lumbar lordosis); and
          2. Member has radiographic findings characteristic of achondroplasia (e.g., large calvaria and narrowing of the foramen magnum region, undertubulated, shortened long bones with metaphyseal abnormalities, narrowing of the interpedicular distance of the caudal spine, square ilia and horizontal acetabula, small sacrosciatic notches, proximal scooping of the femoral metaphyses, and short and narrow chest); or
        2. Molecular genetic testing confirmed c.1138G>A or c.1138G>C variant (i.e., p.Gly380Arg mutation) in the fibroblast growth factor receptor-3 (FGFR3) gene; and
      2. Member has open epiphyses; and
      3. Member did not have limb-lengthening surgery in the previous 18 months and does not plan on having limb-lengthening surgery while on Voxzogo therapy; and
      4. Prescribed by or in consultation with one of the following:
        1. Clinical geneticist; or
        2. Endocrinologist; or
        3. A provider who has specialized expertise in the management of achondroplasia

      Initial authorization duration: 12 months

       

      REAUTHORIZATION CRITERIA Vosoritide (Voxzogo™) is re-approved when ALL of the following are met:

      1. Member continues to have open epiphyses; and
      2. Documentation of positive clinical response to therapy [e.g., improvement in annualized growth velocity (AGV) compared to baseline]; and
      3. Prescribed by or in consultation with one of the following:
        1. Clinical geneticist; or
        2. Endocrinologist; or
        3. A provider who has specialized expertise in the management of achondroplasia

      Reauthorization duration: 12 months


      N/A
      Achondroplasia. UpToDate. December 2023. Available at: https://www.uptodate.com/contents/achondroplasia?search=achondroplasia&source=search_result&selectedTitle=1~89&usage_type=default&display_rank=1. Accessed April 18, 2024.

      Vosoritide (voxzogo) [package insert]. Novato, CA. BioMarin Pharmaceutical Inc. October 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=228e8560-04a4-4bb1-a81f-29531a9e4d27. Accessed April 18, 2024.


      		43/14/202412/18/20247/1/2024 1:31 AMNo presence informationsrv_ppsgw_P
      ​Rx.01.33 Off Label Use
      ​Brand Name​Generic Name
      ​Voxzogo™​vosoritide

      		Voxzogo® vosoritide
      430
        
      		7/1/2024Rx.01.75CommercialOyenusi, OluwadamilolaQ1-2024
      Proton Pump Inhibitors (PPIs) suppress gastric acid secretion by inhibiting hydrogen-potassium adenosinetriphosphatase (H+/K+ ATPase) on the surface of parietal cells, the final step in acid secretion. PPIs are the most potent gastric acid suppression agents and are most effective when the parietal cells are stimulated to produce acid post-prandially.

      PPIs are useful in treating peptic ulcer disease (including prevention and treatment of NSAID induced gastric ulcers), gastroesophageal reflux disease (GERD) with and without esophageal erosions, hypersecretory diseases, and helicobacter pylori infections (as part of an antibiotic containing regimen).

       According to the American College of Gastroenterology's recommendation for the diagnosis and management of GERD, there is "no major difference in efficacy between the different PPIs" when used for an 8-week course to heal erosive esophagitis.  However, no clear recommendation on pharmacologically equivalent doses among the PPIs exists and some individuals report better response to one agent compared to others.

      Vonoprazan suppresses basal and stimulated gastric acid secretion at the secretory surface of the gastric parietal cell through inhibition of the H+, K+-ATPase enzyme system in a potassium competitive manner. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, vonoprazan has been characterized as a type of gastric proton-pump inhibitor, in that it blocks the final step of acid production. Vonoprazan does not require activation by acid. Vonoprazan may selectively concentrate in the parietal cells in both the resting and stimulated states. Vonoprazan binds to the active pumps in a noncovalent and reversible manner.


      VOQUEZNA is a potassium-competitive acid blocker indicated:
      • for healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults. 
      • to maintain healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults.
      • in combination with amoxicillin and clarithromycin for the treatment of Helicobacter pylori (H. pylori) infection in adults.
      • in combination with amoxicillin for the treatment of H. pylori infection in adults.

      The intent of this policy is to communicate the medical necessity criteria for proton pump inhibitors (PPIs), vonoprazan (Voquezna) as provided under the member’s prescription drug benefit.

      ​

      INITIAL CRITERIA Brand proton pump inhibitor capsules and tablets (e.g., Aciphex® tablets, Protonix® tablets, Dexilant® capsules, Prilosec® capsules, Voquezna®), dexlansoprazole, generic esomeprazole or omeprazole-sodium bicarbonate (Konvomep™) is approved when BOTH of the following are met:

      1. An FDA or compendia approved indication; and
      2. Inadequate response to a two-week trial of maximally tolerated dose or inability to tolerate THREE of the following generic proton pump inhibitors:
        1. Omeprazole
        2. Lansoprazole
        3. Pantoprazole
        4. Rabeprazole
      Initial authorization duration: H. Pylori 14 days; all other indications 2 years


      REAUTHORIZATION CRITERIA Brand proton pump inhibitor capsules and tablets (e.g., Aciphex® tablets, Protonix® tablets, Dexilant® capsules, Prilosec® capsules, Voquezna®), dexlansoprazole, generic esomeprazole or omeprazole-sodium bicarbonate (Konvomep™) is re-approved when BOTH of the following are met:
      1. Documentation of positive clinical response to therapy; and
      2. Documentation of continued need for treatment beyond 2 years
      Reauthorization duration: 2 years

      INITIAL CRITERIA Formulations other than capsules or tablets (e.g., lansoprazole [Prevacid® solu-tab], rabeprazole (Aciphex®) Sprinkles, Zegerid® packet, Prilosec® granules for suspension, pantoprazole [Protonix® packets] and esomeprazole [Nexium®] packets) require prior authorization for members aged 12 years and older and are approved when there is documentation of BOTH of the following:

      1. An FDA approved indication or clinically accepted use; and
      2. One of the following:
        1. Drug will be administered via nasogastric or gastrostomy tube; or
        2. Member is unable to swallow an intact capsule or tablet


       Initial authorization duration: H. Pylori 14 days; all other indications 2 years

      REAUTHORIZATION CRITERIA Formulations other than capsules or tablets (e.g. lansoprazole [Prevacid® solutab], rabeprazole [Aciphex®] Sprinkles, Zegerid® packet, Prilosec® granules for suspension, pantoprazole [Protonix® packets] and esomeprazole [Nexium®] packets) require prior authorization for members age 12 years and older and are re-approved when BOTH of the following criteria are met:

      1. Documentation of positive clinical response to therapy; and
      2. Documentation of continued need for treatment beyond 2 years


      Reauthorization duration: 2 years



      None

      Aciphex® (rabeprazole) [prescribing information]. Woodcliffe Lake, NJ: Eisai, Inc; November 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5d103551-978f-472a-9c62-51e6e4dea068&type=display. Accessed April 17, 2024.

      Dexilant® (dexlansoprazole) [package insert]. Deerfield, IL: Takeda Pharmaceuticals America Inc. July 2023. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=9819f033-3bbe-442e-8e92-45fec77b237d&type=display.  Accessed April 17, 2024.

      Esomeprazole strontium [package insert]. Glasgow, KY. Amneal Pharmaceuticals. December 2016. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=61a5a84e-0194-4f11-91f8-83d7ac404932&type=display. Accessed April 17, 2024.

      Katz PO, Gerson LB, Vela MF. Diagnosis and Management of Gastroesophageal Reflux Disease: American College of Gastroenterology. Am J Gastroenterol 2013;108:308-328. DOI: 10.1038/ajg.2012.80. Available from: ACG Clinical Guideline: Guidelines for the Diagnosis and Management of Gastroesophageal Reflux Disease (nih.gov). 

      Konvomep™ (omeprazole and sodium bicarbonate for oral suspension). Woburn, MA. Azurity Pharmaceuticals, Inc. August 2023. Available from: https://konvomep.com/wp-content/uploads/Konvomep-Full-Prescribing-Information.pdf. Accessed April 17, 2024. 

      Laine L, Jensen JM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107:345-60. DOI 10.1038/ajg.2011.480 Available from: http://s3.gi.org/physicians/guidelines/UlcerBleeding.pdf

      Nexium® (esomeprazole) [package insert]. Wilmington DE. AstraZeneca Pharmaceuticals LP. October 2017. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f4853677-1622-4037-688b-fdf533a11d96&type=display. Accessed April 17, 2024.

      Prevacid® (lansoprazole) [package insert]. Deerfield, IL; Takeda Pharmaceuticals America Inc. June 2018. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=71ba78cb-7e46-43eb-9425-fa130f537f84&type=display. Accessed April 17, 2024.

      Prilosec® (omeprazole) [package insert]. AstraZeneca Pharmaceuticals, Wilmington, DE, 2005. December 2016. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a1b077e6-b070-43f2-a98e-380cc635419d&type=display. Accessed April 17, 2024. 

      Protonix® (pantoprazole) [package insert]. Philadelphia, PA: Pfizer; May 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=08098cb2-c048-4640-f387-6beec4a38936&type=display.  Accessed April 17, 2024.  

      Voquezna (vonoprazan) [package insert]. Buffalo Grove, IL: Phathom Pharmaceuticals, Inc. November 2023. Available at: https://www.phathompharma.com/wp-content/uploads/VOQUEZNA-tablets-Prescriber-Information.pdf. Access April 17, 2024.

      Wolfe MM. Overview and comparison of the proton pump inhibitors for the treatment of acid-related disorders. UpToDate. Updated January 2024.  Available from: https://www.uptodate.com. Accessed April 17, 2024.

      Zegerid® [package insert] Raleigh, NC. Salix Pharmaceuticals Inc.; June 2018. [Salix Web site].  Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=cd6868b9-5824-442b-8d65-4db29ecb70a4&type=display. Accessed April 17, 2024.


      		263/14/202412/18/20247/1/2024 1:31 AMNo presence informationsrv_ppsgw_P
      Rx.01.33 Off-Label Use 

      Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit 

      Brand NameGeneric Name
      Aciphex® [Sprinkles]rabeprazole
      Dexilant®dexlansoprazole
      Prevacid® [Solutab]lansoprazole
      Nexium® [Suspension]esomeprazole magnesium
      Prilosec® [Suspension]omeprazole
      Protonix® [Suspension]pantoprazole
      Zegerid® Suspensionomeprazole/sodium bicarbonate
      Konvomep™ Suspensionomeprazole/sodium bicarbonate
      Voqueznavonoprazan

      		Voquezna® vonoprazan
      431
        
      		7/1/2024Rx.01.219CommercialOyenusi, OluwadamilolaQ1-2024

      Parkinson's disease (PD) is a neurodegenerative disorder caused by progressive dopamine depletion in the nigrostriatal pathway of the brain.  PD is characterized by manifestations of tremor, bradykinesia, and rigidity. PD is a motor condition that includes neuropsychiatric and other nonmotor manifestations.

      The dopamine precursor levodopa is the most effective drug for the symptomatic treatment of PD, however; levodopa-induced complications (eg, motor fluctuations [“wearing off" phenomenon], dyskinesia, dystonia) develop in at least 50% of patients after 5 to 10 years of levodopa treatment. The risk of motor complications increases with higher levodopa doses and younger age of PD onset.

      The cause of motor fluctuations is not clear, but it is hypothesized that they evolve as PD progresses because progressive degeneration of the nigrostriatal dopaminergic pathway reduces the ability of nerve terminals to store and release dopamine.  The response to exogenous levodopa becomes more pulse-like due to the inability of the nerve terminals to store and release dopamine.  Levodopa has a short half-life (90 minutes), rapid cycling pharmacokinetics (PK), and erratic intestinal absorption related to slowed intestinal motility.

      The four main drugs or classes of drugs that have anti-parkinson activity are monoamine oxidase type B (MAO B) inhibitors, amantadine, dopamine agonists and levodopa. Initial therapy is individualized and requires a flexible trial-and-error approach. Individuals who exhibit mild symptoms with minimal impact on daily life are good candidates for MAO B inhibitor as initial therapy. For individuals with mild to moderate symptoms that impact daily living, either dopamine agonist or levodopa is recommended in individuals younger than 65; levodopa is preferred in those older than 65 years of age. Levodopa is the drug of choice in individuals with moderate to severe symptoms regardless of age.

      Levodopa, the metabolic precursor of dopamine, crosses the blood-brain barrier and is presumably converted to dopamine in the brain. This is thought to be the mechanism whereby levodopa relieves symptoms of PD

      Levodopa (Inbrija™) inhalation powder is indicated for the intermittent treatment of OFF episodes in patients with PD treated with carbidopa/levodopa. 

      Istradefylline (Nourianz™) is an adenosine receptor antagonist indicated as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson's disease (PD) experiencing “off" episodes. The precise mechanism by which istradefylline exerts its therapeutic effect in PD is unknown.

      The mechanism by which apomorphine hydrochloride treats Parkinson Disease is unknown. Apomorphine is a non-ergoline dopamine agonist that has high in-vitro affinity for the dopamine D4 receptor, and moderate affinity for the dopamine D2, D3, D5, and adrenergic a1D, a2B, and a2C receptors. Activity is suspected to be due to stimulation of post-synaptic dopamine D2-type receptors within the caudate-putamen in the brain.

      Apomorphine hydrochloride (Kynmobi™) sublingual film is a non-ergoline dopamine agonist indicated for the acute, intermittent treatment of “off" episodes in patients with Parkinson's disease (PD).

      Apomorphine hydrochloride (Apokyn®) injection for subcutaneous use is a non-ergoline dopamine agonist indicated for the acute, intermittent treatment of hypomobility, “off" episodes (“end-of-dose wearing off" and unpredictable “on/off" episodes) associated with advanced Parkinson's disease.

      Adding a catechol-O-methyltransferase (COMT) inhibitor can prolong and potentiate the levodopa effect and thereby reduce "off" time when used as adjunctive therapy with levodopa.



      The intent of this policy is to communicate the medical necessity criteria for levodopa inhalation (Inbrija™), istradefylline (Nourianz™), and apomorphine (Apokyn®, Kynmobi™) as provided under the member's prescription drug benefit.
      Adjunctive treatment for Parkinson's Disease

      Parkinson's Disease
       
      INITIAL CRITERIA: Levodopa inhalation (Inbrija™), or istradefylline (Nourianz™) is approved when ALL of the following are met:

      1. Diagnosis of Parkinson's disease and member is experiencing intermittent off episodes; and
      2. Member is 18 years of age or older; and
      3. Concurrent use of carbidopa/levodopa containing product at maximally tolerated dose; and
      4. Prescribed by or in consultation with a neurologist; and
      5. Member had inadequate response or inability to tolerate TWO of the following:
        1. MAO-B Inhibitor (e.g., rasagiline, selegiline); or
        2. Dopamine Agonist (e.g., pramipexole, ropinirole); or
        3. COMT inhibitor (e.g., entacapone)


      Initial authorization duration: 2 years

      REAUTHORIZATION CRITRIA: Levodopa inhalation (Inbrija®), or istradefylline (Nourianz™) is re-approved when ALL of the following are met:

      1. Documentation of positive clinical response to therapy; and
      2. Concurrent use of carbidopa/levodopa containing product

       
      __________________________________________________________________________________________
      Advanced Parkinson's Disease


      INITIAL CRITERIA: Apomorphine (Apokyn®, Kynmobi™) is approved when ALL of the following are met: 

      1. Diagnosis of advanced Parkinson's disease and member is experiencing intermittent "off" episodes; and
      2. Member is 18 years of age or older; and
      3. One of the following:
        1. Member is receiving medication in combination with other medications for the treatment of Parkinson's disease at maximally tolerated dose (e.g., carbidopa/levodopa, pramipexole, ropinirole, etc…); or
        2. Member has a contraindication or intolerance to other medications for the treatment of Parkinson's disease; and
      1. Member is not using the medication with any 5-HT3 antagonist (e.g., ondansetron, granisetron, dolasetron, palonosetron, alosetron); and
      2. For Apomorphine (Apokyn®) inadequate response or inability to tolerate apomorphine (Kynmobi™); and
      3. Prescribed by or in consultation with a neurologist

      Initial authorization duration: 2 years

      REAUTHORIZATION CRITRIA: Apomorphine (Apokyn®, Kynmobi™) is re-approved with documentation of positive clinical response to therapy.

      Reauthorization duration: 2 years


      None

      Apokyn® (apomorphine hydrochloride injection) [prescribing information]. Louisville, KY: US WorldMeds, LLC.; June 2022. Available from: https://www.apokyn.com/sites/all/themes/apokyn/content/resources/Apokyn_PI.pdf. Accessed April 17, 2024.

      Inbrija™ [package insert]. Ardsley, NY. Acorda Therapeutics, Inc. December 2022. Available at: https://www.inbrija.com/prescribing-information.pdf. Accessed April 17, 2024.

      Kynmobi™ (apomorphine hydrochloride sublingual film) [prescribing information]. Marlborough, Massachusetts: Sunovion Pharmaceuticals Inc.; September 2022. Available from: https://www.kynmobi.com/Kynmobi-Prescribing-Information.pdf. Accessed April 17, 2024.

      Nourianz™ [package insert]. Bedminster, NJ. Kyowa Kirin, Inc., May 2020. Available at: https://www.nourianz.com/assets/pdf/nourianz-full-prescribing-information.pdf. Accessed April 17, 2024.

      Chou KL. Clinical manifestations of Parkinson disease. UpToDate Web site. Updated March 2023. www.uptodate.com. Accessed April 17, 2024.

      Fox SH, Katzenschlager R, Lim SY, et al; Movement Disorder Society Evidence-Based Medicine Committee. International Parkinson and Movement Disorder Society evidence-based medicine review: update on treatments for the motor symptoms of Parkinson's disease. Mov Disord. 2018;33(8):1248-1266.

      Grosset DG, Dhall R, Gurevich T, et al. Long-term pulmonary safety of inhaled levodopa in Parkinson's disease subjects with motor fluctuations: a phase 3 open-label randomized study. Poster presented at: 2nd Pan American Parkinson's Disease and Movement Disorders Congress; June 22-24, 2018; Miami, FL.

      Jankovic J. Epidemiology, pathogenesis, and genetics of Parkinson disease. UpToDate Web site. Updated March 223. www.uptodate.com. Accessed April 17, 2024.

      LeWitt PA, Hauser RA, Grosset DG, et al. A randomized trial of inhaled levodopa (CVT-301) for motor fluctuations in Parkinson's disease. Mov Disord. 2016;31(9):1356-65.

      LeWitt PA, Hauser RA, Pahwa R, et al; on behalf of the SPAN-PD Study Investigators. Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol. 2019;18:145-54.

      Oertel WH, Berardelli A, Bloem BR, et al. Late (complicated) Parkinson's disease. In: Gilhus NE, Barnes MP, Brainin M, eds. European Handbook of Neurological Management. West Sussex, United Kingdom: Wiley-Blackwell; 2011:237-267.

      Spindler MA, Tarsy D. Initial pharmacologic treatment of Parkinson disease. UpToDate Web site. Updated March 2023. www.uptodate.com. Accessed April 17, 2024.

      Tarsy D. Medical management of motor fluctuations and dyskinesia in Parkinson disease. UpToDate Web site. Updated March 2023. www.uptodate.com. Accessed April 17, 2024.



      		113/14/20243/14/20257/1/2024 1:31 AMNo presence informationsrv_ppsgw_P
      ​Rx.01.33 Off-Label Use
      ​
      Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit
      Brand NameGeneric Name
      Inbrija™Levodopa inhalation
      Nourianz™Istradefylline
      Apokyn®Apomorphine
      Kynmobi™Apomorphine


      		NANA
      437
        
      		10/1/2024Rx.01.4CommercialOyenusi, OluwadamilolaQ2-2024
      Male hypogonadism is characterized by low testosterone levels.  Primary hypogonadism is characterized by low testosterone levels in the setting of elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations.  Examples of primary hypogonadism include, but are not limited to, Klinefelter syndrome, castration (physical or chemical), and trauma.  Secondary hypogonadism, also referred to as hypogonadotropic hypogonadism, is characterized by low testosterone levels in the setting of normal or low LH and FSH.  In this type of hypogonadism, dysfunction of the hypothalamus or pituitary is the underlying etiology.  Examples of hypogonadotopic hypogonadism include, but are not limited to, idiopathic hypogonadotropic hypogonadism, Kallman syndrome, and pituitary tumors, surgery, or destruction.

      Gender dysphoria, according to the World Professional Association for Transgender Health (WPATH), is defined as the discomfort arising from incongruence between an individual's gender identity and their external sexual anatomy. The standard of care for individuals affected by gender dysphoria include extensive counseling, hormonal therapy and surgery. Androgen hormone therapy is used to induce physical changes to match gender identify in transgender men (female-to-male, FTM). The goal of therapy is to maintain hormone levels in the normal physiological range for the targeted gender, to stop menses and induce virilization, including a male pattern of sexual and facial hair, change in voice, and male physical contours. Both topical and injectable testosterone products are effective for the management of gender dysphoria.

      The active ingredient in all products listed is testosterone. Exogenous testosterone serves to replace testosterone in individuals who are deficient.  Testosterone therapy is indicated for replacement therapy in patients with low testosterone levels due to primary hypogonadism (congenital or acquired) or hypogonadotropic hypogonadism (congenital or acquired). Testosterone enanthate intramuscular injection and methyltestosterone can also be used to stimulate puberty in carefully selected males with clearly delayed puberty. Methyltestosterone is also indicated for the treatment of metastasis from malignant tumor of breast in women 1 to 5 years postmenopausal with inoperable metastatic skeletal disease.

      The intent of this policy is to communicate the medical necessity criteria for Androgel®, Androderm®, Aveed®, Fortesta®, Jatenzo®, Tlando®, Natesto®,  Testim®, Vogelxo®, Xyosted™, Kyzatrex®, and methyltestosterone (Methitest®) as provided under the member’s prescription drug benefit.




      Primary or secondary hypogonadism
      INITIAL CRITERIA: Androgel®, Androderm®, Fortesta®, Natesto®, Testim®, Vogelxo®, Xyosted™, testosterone undecanoate (Jatenzo®, Tlando®, Kyzatrex®, Aveed®), or methyltestosterone (Methitest®) is approved when ALL of the following are met:

      1. Diagnosis of primary or secondary hypogonadism; and
      2. Member is 18 years of age or older; and
      3. ONE of the following:
        1. Negative history of prostate and breast cancer; or
        2. History of prostate cancer status post prostatectomy and documentation that the risk versus benefit has been assessed; and
      4. For Androgel®, Androderm®, Fortesta®, Natesto®, Testim®, Vogelxo®, Xyosted™, testosterone undecanoate (Jatenzo®, Tlando®, Kyzatrex®), methyltestosterone (Methitest®) only, inadequate response or inability to tolerate generic transdermal testosterone; and
      5. For Aveed® only, inadequate response or inability to tolerate generic testosterone injection in oil formulation; and
      6. New users only, low (morning) testosterone level

       
      Initial authorization duration: 2 years


      REAUTHORIZATION CRITERIA Androgel®, Androderm®, Fortesta®, Natesto®, Testim®, Vogelxo®, Xyosted™, testosterone undecanoate (Jatenzo®, Tlando®, Kyzatrex®, Aveed®), methyltestosterone (Methitest®) is re-approved when there is documentation of positive clinical response to therapy.

      Reauthorization duration: 2 years
      _________________________________________________________________________________________
      Gender dysphoria
      INITIAL CRITERIA Androgel®, Androderm®, Fortesta®, Natesto®, Testim®, Vogelxo®, Xyosted™, testosterone undecanoate (Jatenzo®, Tlando®, Kyzatrex®, Aveed®), or methyltestosterone (Methitest®) is approved for use as hormone therapy in children, adolescents, and adults with gender dysphoria when there is documentation of persistent, well-documented gender dysphoria diagnosed in accordance with criteria established in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)

      Initial authorization duration: 2 years
       
      REAUTHORIZATION CRITERIA Androgel®, Androderm®, Fortesta®, Natesto®, Testim®, Vogelxo®, Xyosted™, testosterone undecanoate (Jatenzo®, Tlando®, Kyzatrex®, Aveed®), methyltestosterone (Methitest®) is re-approved when there is documentation of positive clinical response to therapy.

      Reauthorization duration: 2 years
       

       


      Transdermal testosterone (Androgel®, Fortesta®, Testim®, Vogelxo®)

      Secondary exposure: Virilization has been reported in children who were secondarily exposed to transdermal testosterone. Ensure that children avoid contact with unwashed or unclothed application sites in men using transdermal testosterone.  Advise patients to strictly adhere to recommended instructions for use.

      Testosterone enanthate (Xyosted™) and testosterone undecanoate capsule (Jatenzo®, Tlando®, Kyzatrex®)

      Blood pressure increase:

      • Xyosted™, Kyzatrex® and Jatenzo® can cause blood pressure (BP) increases that can increase the risk of major adverse cardiovascular events (MACE), including non-fatal myocardial infarction, non-fatal stroke and cardiovascular death.
      • Before initiating Xyosted™, Kyzatrex® and Jatenzo®, consider the patient's baseline cardiovascular risk and ensure blood pressure is adequately controlled.
      • Periodically monitor for and treat new-onset hypertension or exacerbations of pre-existing hypertension and re-evaluate whether the benefits of Xyosted™, Kyzatrex® and Jatenzo®  outweigh its risks in patients who develop cardiovascular risk factors or cardiovascular disease on treatment.
      • Due to this risk, use Xyosted™, Kyzatrex® and Jatenzo®  only for the treatment of men with hypogonadal conditions associated with structural or genetic etiologies
      Testosterone undecanoate (Aveed®): SERIOUS PULMONARY OIL MICROEMBOLISM (POME) REACTIONS AND ANAPHYLAXIS
      • Serious POME reactions, involving urge to cough, dyspnea, throat tightening, chest pain, dizziness, and syncope; and episodes of anaphylaxis, including life-threatening reactions, have been reported to occur during or immediately after the administration of testosterone undecanoate injection. These reactions can occur after any injection of testosterone undecanoate during the course of therapy, including after the first dose. 
      • Following each injection of Aveed, observe patients in the healthcare setting for 30 minutes in order to provide appropriate medical treatment in the event of serious POME reactions or anaphylaxis.
      • Aveed is available only through a restricted program called the Aveed REMS Program.



      Androderm® (testosterone) [package insert]. Irvine, CA. Allergan USA, Inc. May 2020. Available from: https://www.allergan.com/assets/pdf/androderm_pi. Accessed July 31, 2024. 

      AndroGel® (testosterone) [package insert]. North Chicago, IL. AbbVie. November 2022. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8677ba5b-8374-46cb-854c-403972e9ddf3&type=displayAccessed July 31, 2024. 

      Aveed®(testosterone undecanoate) [package insert]. Malvern, PA. Endo USA. August 2021. Available from: https://d1skd172ik98el.cloudfront.net/48a33315-f594-4269-8043-8853d10fb7bf/d793179d-9cc6-42e4-8428-05a7d7a68525/d793179d-9cc6-42e4-8428-05a7d7a68525_source__v.pdf. Accessed July 31, 2024. 

      Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Jun;95(6):2536-59.

      Fortesta® (testosterone) [package insert]. Malvern, PA. Endo Pharmaceuticals, Inc. June 2020. Available from: http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=053a7300-0bce-11e0-9d16-0002a5d5c51b&type=display. Accessed July 31, 2024. 

      Gooren L . Hormone treatment of the adult transsexual patient. Horm Res. 2005;64(Suppl 2):31–36

      Gooren LJG , Giltay EJ  . Review of studies of androgen treatment of female-to-male transsexuals: effects and risks of administration of androgens to females. J Sex Med . 2008;5(4):765–776.

      Jatenzo® (testosterone undecanoate) capsules [prescribing information]. Northbrook, IL. Clarus Therapeutics, Inc. January 2023. Available from: https://www.jatenzo.com/assets/pdfs/jatenzo-pi.pdf. Accessed July 31, 2024. 

      Kaplan AL, Trinh QD, Sun M, Carter SC, Nguyen PL, Shih YC, Marks LS, Hu JC. Testosterone replacement therapy following the diagnosis of prostate cancer: outcomes and utilization trends. J Sex Med. 2014 Apr;11(4):1063-70.

      Kaufman J, Graydon RJ. Androgen replacement after curative radical prostatectomy for prostate cancer in hypogonadal men. J Urol. 2004;172(3):920-922.

      Kyzatrex® (testosterone undecanoate) [prescribing information]. Raleigh, NC: Marius Pharmaceuticals LLC. September 2022. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7f7167a7-2a25-47e2-acf5-33f499fce971. Accessed July 31, 2024. 

      Matsumoto AM. Diagnosis and evaluation of male hypogonadism. Medscape CME. 2008. Available from: http://www.medscape.org/viewarticle/575491. Accessed July 31, 2024. 

      Meriggiola MC , Gava G  . Endocrine care of transpeople part I. A review of cross-sex hormonal treatments, outcomes and adverse effects in transmen. Clin Endocrinol (Oxf) . 2015;83(5):597–606.

      Methitest® (methyltestosterone) [prescribing information]. Bridgewater, NJ: Amneal Pharmaceuticals LLC.; October 2018. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=77bb4ef4-c10e-4acc-8225-651d003f4561. Accessed July 31, 2024. 

      Meza J, Weaver K, Martin S. FPIN's clinical inquiries. Testosterone therapy and risk recurrence after treatment of prostate cancer. Am Fam Physician. 2013 Oct 15;88(8):Online. Available from: http://www.aafp.org/afp/2013/1015/od5.pdf

      Moore E , Wisniewski A , Dobs A  . Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects. J Clin Endocrinol Metab . 2003;88(8):3467–3473.

      Natesto® (testosterone) [package insert]. Malvern, PA. Endo Pharmaceuticals, Inc. October 2016. Available from: http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b0343bcc-7320-4bf2-bcb3-d95b6f4ba5fe&type=display. Accessed July 31, 2024. 


      Pastuszak AW, Pearlman AM, Lai WS, Godoy G, Sathyamoorthy K, Liu JS, Miles BJ, Lipshults LI, Khera M. Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy. J Urol. 2013 Aug;190(2):639-44. Accessed July 31, 2024. 

      Seftel AD, Mack RJ, Secrest AR, et, al. Restorative increases in serum testosterone levels are significantly correlated to improvements in sexual functioning. J Androl. 2004; 25(6):963-972.

      Steidle C, Schwartz S, Jacoby K, et, al. AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab. 2003; 88(6):2673-2681.

      Testim® (testosterone) [package insert]. Malvern, PA. Auxilium Pharmaceuticals. April 2018. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=9f2aae1f-898d-4955-be31-678e0cf85395&type=display. Accessed July 31, 2024. 

      Testosterone. Micromedex. Available from: http://www.micromedexsolutions.com. Accessed July 31, 2024. 

      Tlando® (testosterone undecanoate) [package insert]. Ewing, NJ. Antares Pharma Inc. February 2024. Available from: https://www.tlando.com/application/files/9416/5366/3764/TLANDO_PI__Medication_Guide__FINAL__032822.pdf#hcpisi. Accessed July 31, 2024. 

      Vogelxo® (testosterone) [package insert]. Maple Grove, MN.  Upsher-Smith Laboraories, Inc. April 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=2dd150f6-cdfd-4d51-8888-12b288f26262&type=display. Accessed July 31, 2024. 

      Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FCW. Investigation, treatment and monitoring of late-onset hypogonadism in males. ISA, ISSAM, EAU, EAA and ASA recommendations. Eur J Endocrinol. 2008 Nov;159(5):507-514.

      Xyosted™ (testosterone enanthate) injection [package insert]. Ewing, NJ. Antares Pharma, Inc. August 2023. Available at: https://www.xyosted.com/PI.pdf. Accessed July 31, 2024. 

      The World Professional Association for Transgender Health. Standards of Care for the Heath of Transsexual, Transgender, and Gender Nonconforming People. 7th version. 2019. Available at: https://www.wpath.org/publications/soc. Accessed July 31, 2024. 


      		257/1/20246/6/202510/1/2024 1:11 AMNo presence informationsrv_ppsgw_P
      Rx.01.33 Off-Label Use

      Brand NameGeneric Name
      Androgel®Testosterone
      Androderm®Testosterone
      Fortesta®Testosterone
      Natesto®Testosterone
      Striant®Testosterone
      Testim®Testosterone
      Vogelxo®Testosterone
      Aveed®, Jatenzo®, Tlando®, Kyzatrex®Testosterone undecanoate
      Testred®, Android®, Methitest®Methyltestosterone
      Xyosted™Testosterone enanthate


      		Androgel®, Androderm®, Aveed®, Fortesta®, Jatenzo®, Tlando®, Natesto®,  Testim®, Vogelxo®, Xyosted™, Kyzatrex®, Methitest®Testosterone, Testosterone undecanoate, Methyltestosterone, Testosterone enanthate
      438
        
      		10/1/2024Rx.01.213CommercialOyenusi, OluwadamilolaQ2-2024
      ​Mycobacterium avium complex (MAC) is the most common pulmonary nontuberculous mycobacterial (NTM) infections of the lung in almost all regions of the world. Antimycobacterial treatment is prolonged and potentially difficult to tolerate and should only be considered in individuals who meet the clinical, radiographic, and microbiologic criteria for the diagnosis of nontuberculous mycobacterial infection. Three-drug combination regimen is recommended for those treated for MAC pulmonary disease and treatment is continued until sputum cultures are consecutively negative for at least 12 months.

      Amikacin liposome inhalation suspension (Arikayce®) is an aminoglycoside antibacterial indicated in adults who have limited or no alternative treatment options, for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen in patients who do not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. As only limited clinical safety and effectiveness data for ARIKAYCE are currently available, reserve ARIKAYCE for use in adults who have limited or no alternative treatment options. This drug is indicated for use in a limited and specific population of patients.

      ​The intent of this policy is to communicate the medical necessity criteria for amikacin liposome inhalation suspension (Arikayce®) as provided under the member's prescription drug benefit.

      INITIAL CRITERIA: Arikayce® (amikacin liposome inhalation suspension) is approved when ALL of the following are met:

      1. Diagnosis of refractory Mycobacterium avium complex (MAC) lung disease; and
      2. Member has not achieved negative sputum cultures after a minimum of 6 consecutive months of multidrug background regimen therapy; and
      3. Documentation that the medication will be used as part of a combination antibacterial regimen; and
      4. Member is 18 years of age or older; and
      5. Prescribed by or in consultation with a pulmonologist or infectious diseases specialist

      Initial authorization duration: 6 months

      REAUTHORIZATION CRITERIA: Arikayce® (amikacin liposome inhalation suspension) is re-approved when both of the following are met:

      1. Documentation of positive clinical response to therapy; and
      2. Documentation that the medication will be used as part of a combination antibacterial regimen

      Reauthorization duration: 12 months


      WARNING: RISK OF INCREASED RESPIRATORY ADVERSE REACTIONS

      ARIKAYCE has been associated with a risk of increased respiratory adverse reactions, including, hypersensitivity pneumonitis, hemoptysis, bronchospasm, and exacerbation of underlying pulmonary disease that have led to hospitalizations in some cases.

      Arikayce® (amikacin liposome inhalation suspension) [prescribing information]. Bridgewater, NJ. Insmed®. February 2023. Available at: https://www.arikayce.com/pdf/full-prescribing-information.pdf. Accessed July 31, 2024.

      Kasperbauer, S. Treatment of Mycobacterium avium complex pulmonary infections in adults. UpToDate Web site. December 2023. www.uptodate.com. Accessed July 31, 2024.

      		67/1/20246/6/202510/1/2024 1:11 AMNo presence informationsrv_ppsgw_P
      Rx.01.33 Off-Label Use
      Brand NameGeneric Name
      Arikayce®Amikacin liposome inhalation suspension

      		Arikayce®amikacin liposome inhalation suspension
      439
        
      		10/1/2024Rx.01.6CommercialOyenusi, OluwadamilolaQ2-2024
      Aztreonam (Cayston®) is a monobactam antibiotic, which is part of the beta-lactam class, that binds to penicillin binding proteins of susceptible bacteria and leads to inhibition of bacterial cell wall synthesis and death of the cell.

      Aztreonam (Cayston®) is indicated to improve respiratory symptoms in cystic fibrosis patients with pulmonary Pseudomonas aeruginosa infections. Safety and effectiveness has not been established in pediatric patients below the age of 7 years, patients with FEV1 <25% or >75% predicted, or patients colonized with Burkholderia cepacia.

      The intent of this policy is to communicate the medical necessity criteria for aztreonam (Cayston®) as provided under the member’s prescription drug benefit.

      INITIAL CRITERIA: Aztreonam (Cayston®) is approved when ALL of the following are met:

      1. Member is 7 years of age or older; and
      2. Diagnosis of cystic fibrosis; and
      3. Evidence of Pseudomonas aeruginosa in the lungs confirmed by culture; and
      4. Susceptibility results indicating that the Pseudomonas aeruginosa is sensitive to aztreonam; and
      5. FEV1 that is 25% to 75% of predicted

      Initial authorization duration: 2 years

      REAUTHORIZATION CRITERIA: Aztreonam (Cayston®) is re-approved when ALL of the following are met:

      1. Diagnosis of cystic fibrosis; and
      2. Evidence of Pseudomonas aeruginosa in the lungs confirmed by culture; and
      3. Documentation of positive clinical response to therapy (e.g. improvement in lung function demonstrated by improved FEV1)

      Reauthorization duration: 2 years


      N/A
      Cayston® [package insert]. Foster City CA. Gilead Sciences. November 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=67300ca3-8c53-4ce4-8e86-2c03be1f9b8a&type=display.  Accessed July 31, 2024.  

      McCoy K, Quittner A, Oermann C, et al. Inhaled Aztreonam Lysine for chronic airway pseudomonas aeruginosa in cystic fibrosis. Am J Respir Crit Care 2008; 178(9): 921-928. Accessed July 31, 2024.   

      Oermann C, Retsch-Bogart G, Quittner A, et al. An 18 month study of the safety and efficacy of repeated courses of inhaled Aztreonam Lysine in Cystic Fibosis. Pediatric Pulmonology2010; 45(11): 1121-1134. Accessed July 31, 2024.  

      Retsch-Bogart G, Quittner A, Gibson R, et al. Efficacy and Safety of inhaled Aztreonam lysine for airway pseudomonas in cystic fibrosis. Chest 2009; 135(5): 1223-1232.  Accessed July 31, 2024.  



      		167/1/20246/6/202510/1/2024 1:12 AMNo presence informationsrv_ppsgw_P
      Rx.01.33 Off-Label Use​



      ​Brand Name​Generic Name
      ​Cayston®​Aztreonam

      		Cayston®Aztreonam
      441
        
      		10/1/2024Rx.01.217CommercialOyenusi, OluwadamilolaQ2-2024
      Neurotrophic keratitis (NK) is a rare degenerative corneal disease caused by impairment in the first branch of the trigeminal nerve which leads to a decrease in or absence of corneal sensitivity. Loss of sensitivity impairs wound healing, leading to corneal epithelial breakdown, development of ulcerations, melting of the stroma, and corneal perforation. Diagnosis, prognosis, and treatment are based on disease severity, which is classified into 3 stages. Stage 1 (mild) NK is characterized by ocular surface irregularity and reduced vision; stage 2 (moderate) is characterized by a non-healing persistent epithelial defect (PED); and stage 3 (severe) exhibits corneal ulceration involving subepithelial (stromal) tissue, which may progress to corneal melting and perforation.  

      Therapy for stage 1 disease aims to prevent epithelial breakdown, generally by administering preservative-free artificial tears and discontinuing all topical and systemic medications associated with ocular surface toxicity. The use of punctal plugs may also help increase tear volume. The goal of treatment for stage 2 NK is to promote healing of the epithelial defect and to avoid the development of a corneal ulcer. In addition to the therapies in the previous stage, topical antibiotics are recommended to prevent infections. Therapeutic corneal or scleral contact lenses may be used to promote healing; however, there may be an increased risk of secondary infections. Autologous serum eye drops, which contain components of natural tears, have increasingly been used to treat ocular surface disorders including NK. The main goal of treatment at stage 3 is to prevent corneal thinning and perforation. Various surgeries and procedures are available to treat ulcers not responding to medical treatment. Tarsorrhaphy is the most commonly used procedure to promote corneal healing. Alternative treatments include botulinum-induced ptosis, amniotic membrane transplantation, eyelid closure with tape, patching, and use of the conjunctival flap to cover the corneal surface.

      Cenegermin-bkbj (Oxervate™) is a novel recombinant human nerve growth factor (rhNGF) produced in Escherichia coli that is structurally identical to human NGF. NGF is an endogenous protein involved in the differentiation and maintenance of neurons, which acts through specific high-affinity and low affinity NGF receptors in the anterior segment of the eye to support corneal innervation and integrity. Cengermin-bkbj (Oxervate™) is indicated for the treatment of neurotrophic keratitis.

      ​The intent of this policy is to communicate the medical necessity criteria for cenegermin-bkbj (Oxervate™) as provided under the member’s prescription drug benefit.




      INITIAL CRITERIA Cenegermin-bkbj (Oxervate™) is approved when ALL of the following are met:

      1. Diagnosis of Stage 2 or 3 neurotrophic keratitis; and
      2. Documentation of an inadequate response or inability to tolerate at least one over-the-counter ocular lubricant used at an optimal dose and frequency for at least two weeks (e.g., artificial tears, lubricating gels/ointments, etc.); and
      3. Prescribed by or in consultation with an ophthalmologist or optometrist; and
      4. Submission of chart documentation indicating treatment of left eye, right eye, or both; and
      5. Member will not exceed 8 weeks of Oxervate therapy per affected eye(s)

      Initial authorization duration: 3 months

      REAUTHORIZATION CRITERIA Cenegermin-bkbj (Oxervate™) is re-approved when ALL of the following are met:

      1. Submission of chart documentation indicating treatment of left eye, right eye, or both; and
      2. One of the following:
        1. Member has received less than or equal to 8 weeks of therapy (one course of therapy) per affected eye(s); and
        2. Documentation of clinical rationale for treatment greater than 8 weeks (e.g., member has a recurrence of neurotropic keratitis in the same eye, or treatment of a different eye); and
      3. Documentation of clinical response to prior Oxervate™ therapy; and
      4. Member will not exceed a total of 16 weeks of Oxervate™ therapy per affected eye(s); and
      5. Prescribed by or in consultation with an ophthalmologist or optometrist

      Reauthorization duration: 3 months

      Lifetime limit: 16 weeks of therapy per affected eye


      N/A
      Bonini S, Lambiase A, Rama P, et al.; REPARO Study Group. Phase II randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis. Ophthalmology. 2018;125(9):1332-1343. Accessed July 31, 2024.

      Dua HS, Said DG, Messmer EM, et al. Neurotrophic keratopathy. Prog Retin Eye Res. 2019; 66:107-131. Accessed July 31, 2024.

      Oxervate® (cenegermin-bkbj) [prescribing information]. Boston, MA: Dompe U.S. Inc. October 2023. Available at:  https://oxervate.com/pdf/PrescribingInformation.pdf. Accessed July 31, 2024.

      Pflugfelder SC, Massaro-Giordano M, Perez VL, Hamrah P, Deng SX, Espandar L, Foster CS, Affeldt J, Seedor JA, Afshari NA, Chao W, Allegretti M, Mantelli F, Dana R. Topical Recombinant Human Nerve Growth Factor (Cenegermin) for Neurotrophic Keratopathy: A Multicenter Randomized Vehicle-Controlled Pivotal Trial. Ophthalmology. 2020 Jan;127(1):14-26. Accessed July 31, 2024.

      Pocobelli A, Komaiha C, De Carlo L, Pocobelli G, Boni N, Colabelli Gisoldi RAM. Role of Topical Cenegermin in Management of a Cornea Transplant in a Functionally Monocular Patient with Neurotrophic Keratitis and Facial Nerve Palsy: A Case Report. Int Med Case Rep J. 2020 Nov 11;13:617-621. Acccessed July 31, 2024.

      Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratisis. Clin Ophthalmol. 2014; 8:571-579. Accessed July 31, 2024.

      Semeraro F, Forbice E, Romano V, et al. Neurotrophic keratitis. Opthalmologica. 2014;231(4):191-197. Accessed July 31, 2024.

      Versura P, Giannaccare G, Pellegrini M, Sebastiani S, Campos EC. Neurotrophic keratitis: current challenges and future prospects. Eye Brain. 2018; 10:37-45. Accessed July 31, 2024.

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      ​Rx.01.33 Off-Label Use
      Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit

      Brand Name
      		Generic Name
      Oxervate™cenegermin-bkbj

      		Oxervate™Cenegermin-bkbj
      443
        
      		10/1/2024Rx.01.134CommercialOyenusi, OluwadamilolaQ2-2024
      The Food and Drug Administration (FDA) defines pharmacy compounding as the practice in which pharmacists combine, mix, or alter ingredients to create unique medications that meet the specific needs of an individual patient. Generally, drugs are compounded for patients that have allergic reactions to inactive ingredients in FDA approved products or for those patients who require a different formulation of a medication that is not commercially available.  

      Compounding pharmacies are regulated by State Boards of Pharmacy and the FDA (if they are outsourcing facilities). For non-outsourcing facilities, drugs can be compounded only if certain conditions are met, such as, valid prescription requirement for an identified individual patient; or in limited quantities before obtaining the actual prescription by the pharmacy. Moreover, FDA restricts the production of essential copies of approved and unapproved non-prescription drugs.

      A compounded product is not considered medically necessary when it replicates a commercially available product (unless the commercially available product is temporarily unavailable), contains a drug product or component that has been removed from the market because it is unsafe or not effective or contains a drug product or component that is excluded from the member's benefit. 

      The intent of this policy is to communicate the medical necessity criteria for compounded products, consistent with Pharmacy Compounding of Human Drug Products Under Sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act, where at least one ingredient is a prescription drug, as provided under the member's prescription drug benefit.

      This policy will also be used to review requests for ingredients which are not considered standard coverage under the prescription drug benefit that are used in compounded products.  This includes requests for injectable medications that are used as part of a compound for a route of administration other than injectable. 

      A compounded product, including a commercially available compounding kit, is considered medically necessary when ALL of the following are met:

      1. The active prescription ingredient(s) of the compound is FDA approved or supported by accepted compendium as stated in the Off-Label Use policy for the indication and route of administration; and
      2. The product as compounded is not commercially available. This may include a current short supply* of the commercially available product or the member has a medical need for a dosage form, strength or formulation other than what can be accomplished with a commercially available product; and
      3. Member had an inadequate response or inability to tolerate all commercially available therapeutic alternatives to treat the condition for which the compound has been requested; and
      4. The compound does not contain any product(s) that were withdrawn or removed from the market due to safety reasons; and
      5. The compound is not used for, nor does it contain, a product that is indicated for an excluded benefit (e.g., cosmetic)
      Additionally, authorization may be placed to allow access to the prescription benefit for products that are not considered standard coverage (e.g. drugs administered intravenously) when all the following are met:
      1. All of the above criteria are for medically necessary are met for the compounded product; and
      2. The product is being used in a compound that will be administered through a route that is considered standard coverage for the prescription benefit (e.g., oral, topical, inhalation, etc.). Bladder installation may be considered if the above criteria are met.
      Authorization length for short supply of the commercially available product will be six months. All other authorizations: 2 years

      * http://www.accessdata.fda.gov/scripts/drugshortages/default.cfm

      * http://www.ashp.org/Drug-Shortages/Current-Shortages


      See labeling for specific ingredients used in a compound.
      American Pharmacists Association. Frequently Asked Questions About Pharmaceutical Compounding. Available from: http://www.pharmacist.com/frequently-asked-questions-about-pharmaceutical-compounding. Accessed July 31, 2024.

      ASHP Guidelines on Outsourcing Sterile Compounding Services. January 2014. Available from:  http://www.ajhp.org/content/71/2/145?sso-checked=true.  July 31, 2024.

      International Academy of Compounding Pharmacist. Available from: http://www.iacprx.org/. Accessed July 31, 2024.

      Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug and Cosmetic Act Guidance. July 2014. Available from:  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pharmacy-compounding-human-drug-products-under-section-503a-federal-food-drug-and-cosmetic-act. Accessed  July 31, 2024.


      Pharmacy Compounding of Human Drug Products Under Section 503B of the Federal Food, Drug and Cosmetic Act. January 2018. Available from http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM510153.pdf. Accessed  July 31, 2024.

      Report: Limited FDA Survey of Compounded Drug Products. June 2018. Available from: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm155725.htm, Accessed  July 31, 2024.

      USP Compounding Standards and Resources.  Available from: http://www.usp.org/usp-healthcare-professionals/compounding?gclid=CJfWt97qmsECFedzMgodCzgA_w. Accessed July 31, 2024.

      		137/1/20246/6/202510/1/2024 1:12 AMNo presence informationsrv_ppsgw_P
      Off Label Use Policy (Rx.01.33)



      ​Product​Description
      ​Compound claims greater than $75Compound where the submitted claim cost is greater than or equal to $75
      ​Various​Compounding Kit

      		Compounded productsCompounded products
      444
        
      		10/1/2024Rx.04.3Claim Payment PolicyOyenusi, OluwadamilolaQ2-2024
      Convenience packs combine two or more individual drug products into a single package.  Products included in a convenience pack may include prescription products, over the counter products, and/or products not approved by the Food and Drug Administration (FDA).   
      The intent of this policy is to communicate the coverage position of convenience packs.

      Coverage is subject to the terms, conditions, and limitations of the member's contract.

      Convenience packs as described above are not covered under the pharmacy benefit because each product is available independently.

       

      A prescriber may issue a prescription or prescriptions for the individual components of the convenience pack.  The individual components will be covered pursuant to the terms of member's benefit.

       

      Examples of convenience packs include, but are not limited to:

       

      • DermacinRx Clorhexacin, which contains the following:
        • Mupirocin 2% ointment – covered as a pharmacy benefit
        • Chlorhexidine gluconate 4% solution, dimethicone 5% cream not covered (not an FDA approved product)
      • Diclovix DM PAK 1.5-8% which contains the following:
        • Diclofenac sodium solution 1.5% - covered as a pharmacy benefit
        • Menthol gel 8% therapy pack – not covered (not FDA approved product)

      N/A
      		107/1/20246/6/202510/1/2024 1:13 AMNo presence informationsrv_ppsgw_P
      Non-FDA approved Products Rx.04.2

      Off-Label Use Rx.01.33

      Convenience Packs
      		Convenience packsConvenience packs
      445
        
      		10/1/2024Rx.01.263CommercialOyenusi, OluwadamilolaQ2-2024
      Vernal keratoconjunctivitis (VKC) is an allergic inflammation of conjunctiva that is bilateral and usually seasonally recurrent. There are three types of vernal conjunctivitis: palpebral (papillae primarily involving upper tarsal conjunctiva), limbal (papillae located at limbus), and mixed (components of both palpebral and limbal types). Histopathologic exam of affected conjunctiva shows small lymphoid follicles composed of increased mast cells, eosinophils, and lymphocytes, mononuclear cells and macrophages, CD4 T lymphocytes and B lymphocytes, fibroblasts, and newly secreted collagen (extracellular matrix components). As disease progresses, cellular infiltration and new collagen deposition form giant papillae (squamous epithelial hyperplasia and dense fibrous tissue containing inflammatory cells). Inflammation of limbal palisades and tarsal conjunctiva produces nodules, due to firm attachments of conjunctiva.

      Cyclosporine is a calcineurin inhibitor immunosuppressant agent when administered systemically. Following ocular administration, cyclosporine is thought to act by blocking the release of pro-inflammatory cytokines such as IL-2. The exact mechanism of action in the treatment of VKC is not known.

      Verkazia® ophthalmic emulsion is a calcineurin inhibitor immunosuppressant indicated for the treatment of vernal keratoconjunctivitis in children and adults.

      ​The intent of this policy is to communicate the medical necessity criteria for cyclosporine ophthalmic emulsion (Verkazia®) as provided under the member's prescription drug benefit. 

      INITIAL CRITERIA Cyclosporine (Verkazia®) is approved when ALL of the following are met:

      1. Diagnosis of moderate to severe vernal keratoconjunctivitis confirmed by the presence of clinical signs and symptoms (e.g., itching, photophobia, giant papillae at the upper tarsal conjunctiva or at the limbus, thick mucus discharge, conjunctival hyperaemia); and
      2. Member is 4 years of age or older; and
      3. Inadequate response or inability to tolerate one of the following:
        1. Topical ophthalmic "dual-acting" mast cell stabilizer and antihistamine (e.g., olopatadine, azelastine); or
        2. Topical ophthalmic mast cell stabilizers (e.g., cromolyn); and
      4. Inadequate response or inability to tolerate short term use (up to 2 to 3 weeks), of topical ophthalmic corticosteroids (e.g., dexamethasone, prednisolone, fluoromethalone); and
      5. Prescribed by or in consultation with one of the following:
        1. Ophthalmologist or
        2. Optometrist

       

      Initial authorization duration: 6 months

       

      REAUTHORIZATION CRITERIA Cyclosporine (Verkazia®) is re-approved when there is documentation of positive clinical response to therapy as evidenced by an improvement in clinical signs and symptoms (e.g., itching, photophobia, papillary hypertrophy, mucus discharge, conjunctival hyperaemia).

       

      Reauthorization duration: 2 years


      N/A
      DynaMed. Vernal Keratoconjunctivitis. EBSCO Information Services. https://www.dynamed.com/condition/vernal-keratoconjunctivitis. Accessed July 31, 2024.

      Verkazia® (cyclosporine) [package insert]. Emeryville, CA: Santen Incorporated; June 2022. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214965s000lbl.pdf. Accessed July 31, 2024.



      		37/1/20246/6/202510/1/2024 1:13 AMNo presence informationsrv_ppsgw_P
      Rx.01.33 Off Label Use

      Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit

      Brand NameGeneric Name
      Verkazia®Cyclosporine ophthalmic emulsion

      		Verkazia®Cyclosporine
      446
        
      		10/1/2024Rx.01.176CommercialOyenusi, OluwadamilolaQ2-2024
      Periodic paralyses are a group of rare, inherited neuromuscular disorders, resulting from mutations in the genes that regulate muscle ion channels.  These disorders are characterized by episodes of painless muscle weakness where the affected muscles become weak and unable to contract.

      The two most common types of periodic paralyses are hypo- and hyper-kalemic.  Hypokalemic periodic paralysis is characterized by a fall in potassium levels in the blood. In individuals with this mutation attacks often begin in adolescence and are triggered by strenuous exercise, high carbohydrate meals, or by injection of insulin, glucose, or epinephrine. Weakness may be mild and limited to certain muscle groups, or more severe and affect the arms and legs. Attacks may last for a few hours or persist for several days. Some patients may develop chronic muscle weakness later in life. Hyperkalemic periodic paralysis is characterized by a rise in potassium levels in the blood. Attacks often begin in infancy or early childhood and are precipitated by rest after exercise, fasting, cold exposure, or ingestion of small amounts of potassium. Attacks are usually shorter, more frequent, and less severe than the hypokalemic form. Muscle spasms are common. Weakness in an attack can be focal, affecting only one limb, but generalized weakness with hypotonia is more common.

      Dichlorphenamide (Keveyis®, Ormalvi®) is an oral carbonic anhydrase inhibitor indicated for the treatment of primary hyperkalemic periodic paralysis, primary hypokalemic periodic paralysis, and related variants. The precise mechanism by which dichlorphenamide exerts its therapeutic effects in patients with periodic paralysis is unknown. 



      The intent of this policy is to communicate the medical necessity criteria for dichlorphenamide (Keveyis®, Ormalvi®) as provided under the member's prescription drug benefit.

      INITIAL CRITERIA: Dichlorphenamide (Keveyis®, Ormalvi®) is approved when of ALL of the following are met:

      1. Treatment of primary hyperkalemic periodic paralysis, primary hypokalemic paralysis, and related variants; and
      2. Prescribed by or in consultation with a neurologist; and
      3. No documentation of ANY of the following:
        1. Concomitant use of high dose aspirin; or
        2. Severe pulmonary disease; or
        3. Hepatic insufficiency; and
      4. Member is 18 years of age or older; and
      5. One of the following:
        1. Member has positive genetic panel for periodic paralysis; or
        2. One of the following tests demonstrated positive results for periodic paralysis:
          1. EMG/nerve conduction studies, or
          2. Long exercise test, or
          3. Muscle biopsy, or
          4. Muscle MRI
      Initial authorization duration: 3 months


      CONTINUAITON CRITERIA: Dichlorphenamide (Keveyis®, Ormalvi®) is reapproved when there is documentation of positive clinical response to therapy as evidenced by a decrease in weekly attack frequency from baseline .

      Continuation authorization duration: 2 years


      N/A
      Dichlorphenamide. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, CO. Available at: http://www.micromedexsolutions.com/. Accessed July 31, 2024.

      Gutmann L, Conwit R. Hyperkalemic periodic paralysis. UpToDate. March 2024.  Available at: https://www.uptodate.com/contents/hyperkalemic-periodic-paralysis. Accessed July 31, 2024.

      Keveyis® (dichlorphenamide) [package insert]. Hawthorne NY. Taro Pharmaceuticals USA, Inc. January 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/011366s030lbl.pdf. Accessed July 31, 2024.

      National Institute of Neurological Disorders and Stroke (NINDS). NINDS Familial Periodic Paralyses Information Page. Available at: https://www.ninds.nih.gov/Disorders/All-Disorders/Familial-Periodic-Paralyses-Information-page. Last updated July 2024. Accessed July 31, 2024.

      Ormalvi® (dichlorphenamide) [package insert]. Cambridge, United Kingdom. February 2024. Available at: https://ormalvi.com/wp-content/uploads/2024/05/ORMALVI-PI-Digital.pdf. Accessed July 31, 2024.


      		107/1/20246/6/202510/1/2024 1:13 AMNo presence informationsrv_ppsgw_P
      Off-Label Use Rx.01.33

      Brand Name

      Generic Name

      Keveyis®, Ormalvi®

      Dichlorphenamide


      		Keveyis®, Ormalvi®Dichlorphenamide
      447
        
      		10/1/2024Rx.01.166CommercialOyenusi, OluwadamilolaQ2-2024
      Droxidopa (Northera®) is indicated for the treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about to black out” in adult patients with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure (Parkinson’s disease, multiple system atrophy, and pure autonomic failure), dopamine beta-hydroxylase deficiency, and non-diabetic autonomic neuropathy.  Effectiveness beyond two weeks of treatment has not been demonstrated. The continued effectiveness of droxidopa should be assessed periodically.

      The exact mechanism of action of droxidopa in the treatment of neurogenic orthostatic hypotension is unknown.  Droxidopa is a synthetic amino acid analog that is directly metabolized to norepinephrine by dopa-decarboxylase, which is extensively distributed throughout the body. Droxidopa is believed to exert its pharmacological effects through norepinephrine and not through the parent molecule or other metabolites.  Norepinephrine increases blood pressure by inducing peripheral arterial and venous vasoconstriction. Droxidopa in humans induces small and transient rises in plasma norepinephrine. Droxidopa is also known as L-dihydroxyphenylserine, or L-DOPS.​

      The intent of this policy is to communicate the medical necessity criteria for droxidopa (Northera®) as provided under the member’s prescription drug benefit.




      INITIAL CRITERIA: Droxidopa (Northera®) is approved when ALL of the following are met:

      1. Diagnosis of symptomatic neurogenic orthostatic hypotension; and
      2. Prescribed by, or in consultation with, ONE of the following:
        1. Cardiologist; or
        2. Neurologist; or
        3. Nephrologist; and
      3. Member is 18 years of age or older; and
      4. Attempt has been made to manage neurogenic orthostatic hypotension through at least one non-pharmacologic intervention (e.g. use of compression stockings/abdominal binder, increasing salt/fluid intake, participation in regular exercise, discontinue or reduce hypotensive or antihypertensive medications); and 
      5. Inadequate response or inability to tolerate midodrine or fludrocortisone; and
      6. For the Brand Northera only, inadequate response or inability to tolerate generic droxidopa

       

      Initial authorization duration: 1 month
       

      REAUTHORIZATION CRITERIA: Droxidopa (Northera®) is re-approved when ALL of the following are met:

      1. Diagnosis of symptomatic neurogenic orthostatic hypotension; and
      2. For the Brand Northera only, inadequate response or inability to tolerate generic droxidopa; and
      3. Prescribed by, or in consultation with, ONE of the following:
        1. Cardiologist; or
        2. Neurologist; or
        3. Nephrologist; and
      4. Documentation of positive clinical response to therapy (e.g. improvement in symptoms such as orthostatic dizziness, lightheadedness, etc.)

      Reauthorization duration: 12 months


      WARNING: SUPINE HYPERTENSION 

      Monitor supine blood pressure prior to and during treatment and more frequently when increasing doses. Elevating the head of the bed lessens the risk of supine hypertension, and blood pressure should be measured in this position. If supine hypertension cannot be managed by elevation of the head of the bed, reduce or discontinue NORTHERA.

      Northera (droxidopa) [package insert]. Deerfield IL. Lundbeck Pharmaceutical LLC. July 2019. Available at:https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=2179f02c-48d7-48eb-8007-5ae43d8d16bc&type=display . Accessed July 31, 2024.

      Droxidopa. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, CO. Available at: http://www.micromedexsolutions.com. Accessed July 31, 2024.

      Freeman R.  Current pharmacologic treatment for orthostatic hypotension. Clinical Autonomic Research 2008; 18(1):14-18. Accessed July 31, 2024.

      Freeman R. Neurogenic orthostatic hypotension. New England Journal of Medicine 2008; 358:615-624. Accessed July 31, 2024.

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      Off-Label Use Rx.01.33

      Generic

      Brand

      Droxidopa

      Northera®

      ​


      		Northera®Droxidopa
      448
        
      		10/1/2024Rx.01.221CommercialOyenusi, OluwadamilolaQ2-2024
      Commercial payers, including managed care organizations and self-funded groups, must ensure appropriate use of drugs in healthcare setting. One way to accomplish this goal is to review claims that exceed a defined threshold.

      Prescription claims with a total cost exceeding $10,000 per claim reject for preliminary review at the point-of-sale with message “claim dollar amount exceeded", requiring the dispensing pharmacist to contact the pharmacy benefit manager. This will apply to any claim that exceeds $10,000, allowing them to be reviewed for clinical appropriateness prior to dispensing. For drugs not meeting approval criteria per Off-Label Use policy, the use for which the drug was prescribed would be deemed experimental/investigational.  

      The intent of this policy is to communicate the medical necessity criteria for claims exceeding $10,000 as provided under the member's prescription benefit.

      Claims that exceed $10,000 are approved when the use, including indication, dose, frequency, quantity, and duration, for the requested drug is approved by the FDA or considered medically accepted per Off-Label Use policy.


      Authorization duration: 2 years, or for the duration of applicable medical necessity approval (for submitted cost plus $3000) 


      N/A
      Academy of Managed Care Pharmacy® (AMCP). Where We Stand - Fraud, Waste and Abuse in Prescription Drug Benefits. Revised February 20243. Available at: https://www.amcp.org/legislative-regulatory-position/fraud-waste-and-abuse-prescription-drug-benefits. Accessed July 31, 2024.
      		67/1/20246/6/202510/1/2024 1:13 AMNo presence informationsrv_ppsgw_P
      Off Label Use Policy Rx.01.33
      Compounded Products Rx.01.134
      Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit Rx.01.76

      ​Drug claims where total drug cost exceeds $10,000
      		claims exceeding $10,000claims exceeding $10,000
      449
        
      		10/1/2024Rx.01.255CommercialOyenusi, OluwadamilolaQ2-2024
      Chronic kidney disease exacerbates the cardiovascular risk associated with type 2 diabetes.

      Mineralocorticoid receptor overactivation is associated with kidney and cardiovascular diseases, through inflammation and fibrosis that lead to progressive kidney and cardiovascular dysfunction.

      Finerenone is a nonsteroidal, selective antagonist of the mineralocorticoid receptor (MR), which is activated by aldosterone and cortisol and regulates gene transcription. Finerenone blocks MR mediated sodium reabsorption and MR overactivation in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, and blood vessels) tissues. MR overactivation is thought to contribute to fibrosis and inflammation. Finerenone has a high potency and selectivity for the MR and has no relevant affinity for androgen, progesterone, estrogen, and glucocorticoid receptors.

      Kerendia® (finerenone) is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adult patients with chronic kidney disease associated with type 2 diabetes.

      The intent of this policy is to communicate the medical necessity criteria for finerenone (Kerendia®) as provided under the member's prescription drug benefit.




      INITIAL CRITERIA Finerenone (Kerendia®) is approved when ALL of the following are met:

      1. Diagnosis of chronic kidney disease (CKD) associated with type 2 diabetes (T2D); and
      2. Urine albumin-to-creatinine ratio (UACR) greater than or equal to 30 mg/g; and
      3. Estimated glomerular filtration rate (eGFR) greater than or equal to 25 mL/min/1.73 m2; and
      4. Serum potassium level less than or equal to 5.0 mEq/L prior to initiating treatment; and
      5. Member is 18 years of age or older; and
      6. One of the following:
        1. Minimum 30-day supply trial of a maximally tolerated dose and will continue therapy with ONE of the following:
          1. Generic angiotensin-converting enzyme (ACE) inhibitor (e.g., benazepril, lisinopril); or
          2. Generic angiotensin II receptor blocker (ARB) (e.g., losartan, valsartan); or
          3. Sodium-glucose cotransporter-2 (SGLT2) inhibitor (e.g., Jardiance, Farxiga); or
        2. Member has contraindication or intolerance to ACE inhibitors, ARBs or SGLT2; and

      Initial authorization duration: 2 years

      REAUTHORIZATION CRITERIA Finerenone (Kerendia®) is re-approved with documentation of positive clinical response to therapy (e.g., reduced incidence of a sustained declined in eGFR, kidney failure, or renal death)

      Reauthorization duration: 2 years


      N/A
      Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;385(24):2252-2263. doi: 10.1056/NEJMoa2110956. Accessed July 31, 2024.

      Kerendia® (finerenone) [package insert]. Whippany, NJ: Bayer HealthCare Pharma, Inc.; September 2022. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215341s000lbl.pdf. Accessed July 31, 2024.

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      Rx.01.33 Off Label Use

      Brand Name

      Generic Name

      ​Kerendia®

      ​finerenone


      		Kerendia®Finerenone
      450
        
      		10/1/2024Rx.01.229CommercialOyenusi, OluwadamilolaQ2-2024
      The life cycle of HIV can be broken down into 6 steps: (1) entry (binding and fusion), (2) reverse transcription, (3) integration, (4) replication (transcription and translation), (5) assembly, and (6) budding and maturation. The identification and understanding of these processes have provided the basis for antiretroviral agents used to treat HIV.

      Antiretroviral agents are the standard of care for treating HIV infections. Antiretroviral therapies with different mechanism of action are usually taken in combination to suppress viral load, improve CD4 cell count, prolong survival, and reduce risk of transmitting HIV to others. Viral failure is defined as patients who had viral loads greater than 400 copies/mL and no viable antiretroviral combination therapy available due to failing at least four of six antiretroviral classes.

      Fostemsavir is a prodrug without significant biochemical or antiviral activity that is hydrolyzed to the active moiety, temsavir, which is an HIV-1 attachment inhibitor. Temsavir binds directly to the gp120 subunit within the HIV-1 envelope glycoprotein gp160 and selectively inhibits the interaction between the virus and cellular CD4 receptors, thereby preventing attachment. Additionally, temsavir can inhibit gp120-dependent post-attachment steps required for viral entry into host cells

      Rukobia (fostemsavir), in combination with other antiretroviral(s), is indicated for the treatment of HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations.

      Enfuvirtide is an antiretroviral drug that interferes with the entry of HIV-1 into cells by inhibiting fusion of viral and cellular membranes. Enfuvirtide binds to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein and prevents the conformational changes required for the fusion of viral and cellular membranes.

      Fuzeon (enfuvirtide) in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy.

      ​The intent of this policy is to communicate the medical necessity criteria for Rukobia® (fostemsavir) and Fuzeon® (enfuvirtide) as provided under the member's prescription drug benefit.

      INITIAL CRITERIA: Fostemsavir (Rukobia®) is approved when ALL of the following are met:

      1. Diagnosis of HIV-1; and 
      2. Member is 18 years of age or older; and 
      3. Will be used in combination with other antiretroviral(s); and 
      4. Member is treatment-experienced with multi-drug resistant HIV-1 infection; and
      5. Member is failing their current antiretroviral regimen due to resistance, intolerance, or safety concerns.

       
      Initial Authorization duration: 12 months

      CONTINUATION CRITERIA: Fostemsavir (Rukobia®) is re-approved when there is documentation of positive clinical response to therapy (e.g., decrease in viral load from baseline; HIV-1 RNA <200 copies/mL was achieved; increase in CD4+ cell count over time)

      Continuation authorization duration: 2 years

      INITIAL CRITERIA: Enfuvirtide (Fuzeon®) is approved when ALL of the following are met: 

      1. Diagnosis of HIV-1; and
      2. Member weighs at least 11kg; and
      3. Will be used in combination with other antiretroviral(s); and
      4. Member is treatment experienced; and
      5. Member is experiencing HIV-1 replication despite ongoing antiretroviral therapy

       
      Initial authorization duration: 12 months

      CONTINUATION CRITERIA: Enfuvirtide (Fuzeon®) is re-approved when there is documentation of positive clinical response to therapy (e.g., decrease in viral load from baseline; HIV-1 RNA <200 copies/mL was achieved; increase in CD4+ cell count over time)

      Continuation authorization duration: 2 years


      N/A
      Rubkobia® (fostemsavir) [package insert]. Research Triangle Park, NC: ViiV Healthcare; February 2024. Available from: https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Rukobia/pdf/RUKOBIA-PI-PIL.PDF. Accessed July 31, 2024.

      Henrich TJ, Kuritzkes DR. HIV-1 entry inhibitors: recent development and clinical use. Curr Opin Virol. 2013;3(1):51-57. doi:10.1016/j.coviro.2012.12.002. Accessed July 31, 2024.

      Centers for Disease Control and Prevention. Estimated HIV incidence and prevalence in the United States, 2018–2022. HIV Surveillance Supplemental Report 2024;29(No. 1). https://stacks.cdc.gov/view/cdc/156513. Published May 2024. Accessed July 31, 2024.

      Kozal M, Aberg J, Pialoux G, et al. Rostemsavir in Adults with Multidrug-Resistant HIV-1 infection, N Eng J Med. 2020 26 March; 382:1232-1243. Accessed July 31, 2024.

      Rukobia (fostemsavir), Micromedex. Accessed July 31, 2024.

      Fuzeon (enfuvirtide) prescribing information. South San Francisco (CA): Genentech, Inc.; December 2019. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6935e846-d5a1-49e5-89a2-f8ebe4d5590d#S12.4. Accessed July 31, 2024.

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      ​Rx.01.33 Off Label Use
      Brand NameGeneric Name
      Rukobia®Fostemsavir
      Fuzeon®Enfuvirtide

      		Rukobia®, Fuzeon®Fostemsavir, Enfuvirtide
      451
        
      		10/1/2024Rx.01.174CommercialOyenusi, OluwadamilolaQ2-2024
      Heart failure affects approximately 5.1 million Americans.  While survival after a diagnosis of heart failure has improved, it is still about 50% at 5 years after diagnosis.  In patients with symptomatic heart failure and left ventricular ejection fraction (LVEF) < 40%, current guidelines recommend angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB), beta blockers, sodium-glucose cotransporter-2 (SGLT-2), and mineralcorticoid receptor antagonist (MRA) as standard of care.  With the exception of diuretics, these classes of medications decrease mortality from heart failure with reduced EF.  Diuretics provide symptomatic relief, however the effects of diuretics on morbidity and mortality are not known.

      Ivabradine reduces spontaneous pacemaker activity at the cardiac sinus node by blocking the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel to selectively inhibit If-current, thus reducing the heart rate. Ventricular repolarization and myocardial contractility are not affected.  Increased heart rate is an ineffective compensatory mechanism and is recognized as an independent risk factor in heart failure. 
       
      Corlanor® (ivabridine) is indicated to reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure  with reduced left ventricular ejection fraction and for the treatment of stable symptomatic heart failure due to dilated cardiomyopathy in pediatric patients ages 6 months and older.
       
      Ivabradine is also indicated for the treatment of stable symptomatic heart failure due to dilated cardiomyopathy in pediatric patients who are in sinus rhythm with an elevated heart rate.

      Vericiguat is a stimulator of soluble guanylate cyclase (sGC), an important enzyme in the nitric oxide (NO) signaling pathway. When NO binds to sGC, the enzyme catalyzes the synthesis of intracellular cyclic guanosine monophosphate (cGMP), a second messenger that plays a role in the regulation of vascular tone, cardiac contractility, and cardiac remodeling. Heart failure is associated with impaired synthesis of NO and decreased activity of sGC, which may contribute to myocardial and vascular dysfunction. By directly stimulating sGC, independently of and synergistically with NO, vericiguat augments levels of intracellular cGMP, leading to smooth muscle relaxation and vasodilation.
       
      Verquvo® (vericiguat) is indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization following a hospitalization for heart failure or need for outpatient IV diuretics, in adults with symptomatic chronic HF and ejection fraction less than 45%.

      The intent of this policy is to communicate the medical necessity criteria for Corlanor® (ivabradine) and Verquvo™ (vericiguat) as provided under the member's prescription drug benefit.

      Chronic heart failure
      INITAL CRITERIA: Corlanor® (ivabradine) is approved when ALL of the following are met:

      1. Diagnosis of stable, symptomatic chronic heart failure; and
      2. Member has New York Heart Association (NYHA) Class II, III, or IV symptoms; and
      3. Member is 18 years of age or older; and
      4. Left ventricular ejection fraction (LVEF) ≤ 35%; and
      5. Sinus rhythm with resting heart rate ≥ 70 beats per minute; and
      6. Member is clinically stable for at least 4 weeks on an optimized and stable clinical regimen which includes ALL of the following:
        1. Maximally tolerated doses of beta blockers (i.e., bisoprolol, carvedilol, metoprolol succinate ER) or inability to tolerate these beta blockers; and
        2. ACE inhibitors, ARBs or angiotensin receptor-neprilysin inhibitor (ARNI) (e.g., Entresto) inability to tolerate ACE inhibitor or ARB or ARNI; and
        3. Sodium-glucose cotransporter-2 (SGLT-2) (e.g., Jardiance, Farxiga); and
        4. Mineralcorticoid receptor antagonist (MRA) (e.g., spironolactone, eplerenone); and
      7. Prescribed by or in consultation with a cardiologist

       
      INITIAL CRITERIA: Vericiguat (Verquvo™) is approved when ALL of the following are met:

      1. Diagnosis of chronic heart failure; and
      2. Member is age 18 or older; and
      3. Member has an ejection fraction of less than 45 percent; and
      4. Member has New York Heart Association (NYHA) Class II, III or IV symptoms; and
      5. One of the following:
        1. Member was hospitalized for heart failure within the last 6 months; or
        2. Member used outpatient intravenous diuretics (e.g., bumetanide, furosemide) for heart failure within the last 3 months; and
      6. Inadequate response or inability to tolerate ALL of the following at a maximally tolerated dose:
        1. One of the following:
          1. Angiotensin converting enzyme (ACE) inhibitor (e.g., captopril, enalapril); or
          2. Angiotensin II receptor blocker (ARB) (e.g., candesartan, valsartan); or
          3. Angiotensin receptor-neprilysin inhibitor (ARNI) [e.g., Entresto (sacubitril and valsartan)]; and
        2. Beta blocker (i.e.., bisoprolol, carvedilol, metoprolol succinate ER; and
        3. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (e.g., Jardiance, Farxiga); and
        4. Mineralcorticoid receptor antagonist (MRA) (e.g., spironolactone, eplerenone); and
      7. Prescribed by or in consultation with a cardiologist 

      Initial authorization duration: 2 years
       
      REAUTHORIZATION CRITERIA: Vericiguat (Verquvo™) or ivabradine (Corlanor®) is re-approved when there is documentation of positive clinical response to therapy.

      Reauthorization duration: 2 years
      _________________________________________________________________________________________
      Inappropriate sinus tachycardia

      INITIAL CRITERIA: Ivabradine (Corlanor®) is approved when ALL of the following are met: 

      1. Diagnosis of inappropriate sinus tachycardia confirmed by both of the following:
        1. Sinus heart rate greater than 100 beats per minute at rest; and
        2. Mean 24-hour heart rate greater than 90 beats per minute; and 
      2. Member is 18 years of age or older; and 
      3. Documentation that other causes of sinus tachycardia have been ruled out (e.g., hyperthyroidism, anemia, illicit stimulant drug use, caffeine, etc.); and
      4. Inadequate response or inability to tolerate one beta-blocker; and 
      5. Prescribed by or in consultation with a cardiologist 

       
      Initial authorization duration: 2 years 

      REAUTHORIZATION CRITERIA: Ivabradine (Corlanor®) is re-approved when there is documentation of positive clinical response to therapy. 

      Reauthorization duration: 2 years 
      _________________________________________________________________________________________
      Heart failure due to dilated cardiomyopathy 

      INITIAL CRITERIA: Ivabradine (Corlanor®) is approved when ALL of the following are met: 

      1. Diagnosis of stable, symptomatic heart failure due to dilated cardiomyopathy; and 
      2. Member has New York Heart Association (NYHA) Class II, III, or IV symptoms; and
      3. Member is 6 months of age to 18 years of age; and 
      4. Member is in sinus rhythm; and 
      5. Member has elevated heart rate; and 
      6. Prescribed by or in consultation with a cardiologist; and
      7. Inadequate response or inability to tolerate to one of the following:
        1. Beta blocker (e.g., bisoprolol, metoprolol succinate extended release)
        2. Angiotensin-converting enzyme (ACE) inhibitor (e.g., captopril, enalapril)
        3. Diuretic Agent (e.g., spironolactone, furosemide)

      Initial authorization duration: 2 years 

      REAUTHORIZATION CRITERIA: Ivabradine (Corlanor®) is re-approved when there is documentation of positive clinical response to therapy. 

      Reauthorization duration: 2 years 


      Vericiguat (Verquvo™): WARNING EMBRYO-FETAL TOXICITY 

      Do not administer VERQUVO to a pregnant female because it may cause fetal harm. Females of reproductive potential: Exclude pregnancy before the start of treatment. To prevent pregnancy, females of reproductive potential must use effective forms of contraception during treatment and for one month after stopping treatment.

      Borer JS, Bohm M, Ford I, et al. Efficacy and safety of ivabradine in patients with severe chronic systolic heart failure (from the SHIFT study). Am J Cardiol. 2014;113:497-503. Accessed July 31, 2024.

      Corlanor (ivabradine) [package insert]. Thousand Oaks, CA: Amgen, Inc. August 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=92018a65-38f6-45f7-91d4-a34921b81d0d&type=display. Accessed July 31, 2024.

      Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics-2013 update: a report from the American Heart Association. Circulation. 2013. Doi: 10.1161/CIR.0b013e31828124ad. Available from: http://circ.ahajournals.org/content/127/1/e6.full.pdf+html. Accessed July 31, 2024.

      Ivabradine. Micromedex. Available from: http://www.micromedexsolutions.com/. Accessed July 31, 2024.

      Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376 (9744):875-85. Accessed July 31, 2024.

      Yancy CW, Jessup M, Bozkurk B, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013. Doi: 10.1016/j.jacc.2013.05.020. Available from: http://circ.ahajournals.org/content/128/16/e240.full.pdf+html. Accessed July 31, 2024.

      Yancy CW, Jessup M, Bozkurk B, et al.ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update to the 2013 ACC/AHA Guidelines for the Management of Heart Failure. Circulation. 2016. DOI: 10.1161/CIR.0000000000000435. Available from: http://circ.ahajournals.org/content/circulationaha/early/2016/05/18/CIR.0000000000000435.full.pdf. Accessed July 31, 2024.

      Cappato R, Castelvecchio S, Ricci C, et. Al. Clinical Efficacy of Ivabradine in Patients with Inappropriate Sinus Tachycardia. Journal of the American College of Cardiology. Vol. 60, No 15, 2012. October 9, 2012: 1323-9. Accessed July 31, 2024.

      Olshansky B, Sullivan R. Inappropriate Sinus Tachycardia. Journal of the American College of Cardiology. Vol. 61, No 8, 2013. February 26, 2013:793-801. Accessed July 31, 2024.

      Sheldon RS, Grubb BP, Olshansky B, et. Al. 2015 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Treatment of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia, and Vasovagal Syncope. Available at: https://www.hrsonline.org/Policy-Payment/Clinical-Guidelines-Documents/2015-HRS-Document-on-POTS-IST-VVS. Accessed July 31, 2024.

      Verquvo™ (vericiguat) [prescribing information]. Whitehouse Station (NJ); Merck & Co. Inc.; July 2023. Available at: https://www.merck.com/product/usa/pi_circulars/v/verquvo/verquvo_pi.pdf. Accessed July 31, 2024.

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      Rx.01.33 Off-Label Use

      Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit

      Brand NameGeneric Name
      Corlanor®ivabradine
      Verquvo™vericiguat

      		Corlanor®, Verquvo™ ivabradine, vericiguat
      452
        
      		10/1/2024Rx.01.149CommercialQ2-2024
      Hemophilia is a bleeding disorder caused by clotting factor deficiencies.  Hemophilia is a rare X-linked, congenitally acquired disease that leads to a deficiency in coagulation factor, VIII (hemophilia A) or IX (hemophilia B).  Hemophilia A or B occurs in approximately 1 out of  10,000 births.  Hemophilia A is more common than hemophilia B, representing approximately 80-85% of hemophilia cases. The disorder is further characterized by the percentage of serum clotting factor activity as compared to the normal range:


      • Severe hemophilia: clotting factor levels are less than 1% of normal
      • Moderate hemophilia: clotting factor levels are 1-5% of normal
      • Mild hemophilia: clotting factors are 5-40% of normal

      Treatment of hemophilia generally involves an infusion of the deficient factors to allow for more normalized clotting response and decreased incidence of uncontrolled bleeding events.

      Treatment regimens are individualized based on disease severity and may include prophylactic infusions of clotting factors, on demand infusions of clotting factors, or a combination of both.  Perioperative infusions are also part of the treatment regimen.

      While Hemophilia A and hemophilia B are the most common types of hemophilia, 1 in every 500,000 to 2 million people have coagulation disorders caused by deficiencies in clotting factors other than factor VIII or IX. The products listed below include those with indications to treat these rare forms of coagulation disorders.

       
      DrugFactorHemophilia AHemophilia BAcquired hemophiliaVon Willebrand diseaseCongenital fibrinogen deficiencyHereditary factor X deficiencyCongenital factor XIII deficiencyControl of bleeding episodes, on demandPerioperative managementRoutine prophylaxis
      Advate®Recombinant factor VIIIX​​​​​​XXX
      Adynovate®Recombinant factor VIII, PEGylatedX​​​​​​XXX
      Afstyla®Recombinant Factor VIIIX​​​​​​XXX
      Alphanate®Factor VIII/ von Willebrand factor complex, humanX​​X (in certain circumstances)​​​XXX
      Alphanine SD®Factor IX, human​X​​​​​XXX
      Alprolix®Recombinant factor IX, Fc fusion protein​X​​​​​XXX
      Altuviiio™

      Recombinant Fc-VWF-XTEN fusion

      protein-ehtl

      		X      XXX
      Benefix®Factor IX, recombinant​X​​​​​XXX
      Coagadex®Factor X, human​​​​​X​XX​
      Corifact®Factor XIII concentrate, human​​​​​​X​XX
      Eloctate®Recombinant factor VIII, Fc fusion proteinX​​​​​​XXX
      Esperoct®Recombinant, glycopegylated-exeiX      XXX
      Feiba [NF] ®Anti-inhibitor coagulant complexX (with inhibitors)X (with inhibitors)​​​​​XXX
      Hemlibra®Factor IXa/ factor X, directed antibodyX        X
      Hemofil M®Factor VIII, humanX​​​​​ XXX
      Humate P®Factor VIII/ von Willebrand factor complex, humanX​​X (in certain circumstances)​​​XXX
      Idelvion®Factor IX, recombinant albumin fusion protein​X​​​​​XXX
      Ixinity®Factor IX, recombinant​X​​​​​XXX
      Jivi®Recombinant, PEGylated, Factor VIIIX      XXX
      Koate DVI®Factor VIII, humanX​​​​​​XXX
      Kogenate FS®Recombinant factor VIIIX​​​​​​XXX
      Kovaltry®Recombinant factor VIIIX​​​​​​XXX
      Novoeight®Recombinant factor VIIIX​​​​​​XXX
      Novoseven RT®Recombinant factor VIIaXXX​​​​XX​
      Nuwiq®Recombinant factor VIIIX​​​​​​XXX
      Obizur®Recombinant factor VIII, porcine sequence​​X​​​​X​​
      Profilnine®Factor IX, human​X​​​​​X​X
      Rebinyn®Recombinant Factor IX X     XX 
      Recombinate®Recombinant factor VIIIX​​​​​​XXX
      Riastap®Fibrinogen concentrate, human​​​​X​​X​​
      Rixubis®Factor IX, recombinant​X​​​​​XXX
      Sevenfact®Factor VIIa, recombinantXX        
      Tretten®Factor XIII A subunit, recombinant​​​​​​X (A subunit)​​X
      Vonvendi®Von Willebrand Factor Recombinant​​​X​​​X​​
      Wilate® von Willebrand/ factor VIII complex, human​​​X​​​X​​
      Xyntha® [Solufuse]Recombinant factor VIIIX​​​​​​XXX


      The intent of this policy is to communicate the medical necessity criteria for Advate®, Adynovate®, Afstyla®, Alphanate®, Alphanine SD®, Alprolix®, Altuviiio™, Benefix®, Coagadex®, Corifact®, Eloctate®, Esperoct®, Feiba NF®, Hemlibra®, Hemofil M®, Humate P®, Idelvion®, Ixinity®, Jivi®, Koate DVI®, Kogenate FS®, Kovaltry®, Novoeight®, Novoseven RT®, Nuwiq®, Obizur®, Profilnine®, Rebinyn®, Recombinate®, Riastap®, Rixubis®, Sevenfact®, Tretten®, Vonvendi®, Wilate®, and Xyntha®/Xyntha® SolofuseTM as provided under the member's prescription drug benefit.

      Advate®, Adynovate®, Afstyla®, Alphanate®, Alphanine SD®, Alprolix®, Altuviiio™, Benefix®, Coagadex®, Corifact®, Eloctate®, Esperoct®, Feiba NF®, Hemlibra®, Hemofil M®, Humate P®, Idelvion®, Ixinity®, Jivi®, Koate DVI®, Kogenate FS®, Kovaltry®, Novoeight®, Novoseven RT®,Nuwiq®, Obizur®, Profilnine®, Rebinyn®, Recombinate®, Riastap®, Rixubis®, Sevenfact®, Tretten®, Vonvendi®, Wilate®, Xyntha®/Xyntha® Solofuse are approved when there is a diagnosis of an FDA approved indication

       

      Approval duration: 2 years 


      Feiba® NF
      Thrombotic/Thromboembolic events: Thrombotic and thromboembolic events have been reported during postmarketing surveillance following infusion of anti-inhibitor coagulant complex, particularly following the administration of high doses and/or in patients with thrombotic risk factors. Monitor patients receiving anti-inhibitor coagulant complex for signs and symptoms of thromboembolic events.
       

      Hemlibra®
      Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate was administered for 24 hours or more to patients receiving HEMLIBRA prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if aPCC is administered. Discontinue aPCC and suspend dosing of HEMLIBRA if symptoms occur.
       
      Novoseven®, Sevenfact®
      Serious arterial and venous thrombotic events following administration of Novoseven and Sevenfact RT have been reported.  Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive Novoseven and Sevenfact RT.  Monitor patients for signs and symptoms of activation of the coagulation system and for thrombosis.

      		237/1/20246/6/202510/1/2024 1:14 AMNo presence informationsrv_ppsgw_P
      453
        
      		10/1/2024Rx.01.100CommercialOyenusi, OluwadamilolaQ2-2024
      In the United States, it is estimated that 2.7 to 3.9 million people are chronically infected with HCV. Chronic HCV infection occurs after acute infection with the virus. It is estimated that approximately 75%-85% of acute infections become chronic. The remaining 15%-25% clear the virus without treatment and do not develop chronic HCV. Genotype (GT) 1 is the most prevalent, with the breakdown as follows: GT 1a: 46.2%, GT1b: 26.3%, GT2: 10.7%, GT3: 8.9%, GT4: 6.3%, GT6: 1.1%, mixed GT/ other: 0.5%. 

      The goal of treating chronic HCV is to "reduce all-cause mortality and liver-related health adverse consequences, including end-stage liver disease and hepatocellular carcinoma, by the achievement of virologic cure as evidenced by a sustained virologic response (SVR)." SVR is defined as the "continued absence of detectable HCV RNA at least 12 weeks after completion of therapy" and is considered a marker for cure of HCV. Several benefits are associated with HCV cure, including decreases in liver inflammation, progression to liver fibrosis, hepatocellular carcinoma, liver-related mortality and liver transplantation. 

      This policy follows the AASLD/IDSA guidelines.  Current treatment regimens consist of at least 2 agents.  Monotherapy is not recommended. 

      Elbasvir/ grazeprevir (Zepatier®) is a product containing an HCV NS5A inhibitor (elbasvir) and an HCV NS3/4A protease inhibitor in a fixed dose combination.

      Glecaprevir/pibrentasvir (Mavyret™) is a fixed-dose combination of glecaprevir, an HCV NS2/4A inhibitor, and pibrentasvir, an HCV NS5A inhibitor.  

      Ledipasvir/ sofosbuvir (Harvoni®) is a combination product that contains an HCV NS5A replication inhibitor (ledipasvir) and an HCV NS5B RNA-dependent polymerase inhibitor (sofosbuvir) in a fixed dose combination. 

      Ombitasvir/ paritaprevir/ ritonavir and dasabuvir (Viekira Pak®) is a combination product that contains an HCV NS5A replication inhibitor (ombitasivir), an HCV NS3/4A protease inhibitor (parataprevir) and a booster (ritonavir) as a fixed dose tablet along with an HCV NS5B RNA-dependent RNA polymerase inhibitor (dasabuvir) as a separate tablet.   

      Sofosbuvir (Sovaldi®) inhibits HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication. 

      Sofosbuvir/velpatasvir/voxilaprevir (Vosevi®) is a fixed-dose combination of sofosbuvir, an HCV nucleotide analog NS5B polymerase inhibitor; velpatasvir, an HCV NS5A inhibitor; and voxilaprevir, an HCV NS3/4A protease inhibitor. 

      Velpatisvir/ sofosbuvir (Epclusa®) is a combination product that contains an HCV NS5A replication inhibitor (velpatisvir) and an HCV NS5B RNA-dependent polymerase inhibitor (sofosbuvir) in a fixed dose combination.​




      The intent of this policy is to communicate the medical necessity criteria for elbasvir/ grazeprevir (Zepatier®), ledipasvir/ sofosbuvir (Harvoni®), ombitasvir/ paritaprevir/ ritonavir and dasabuvir (Viekira Pak®), sofosbuvir (Sovaldi®), velpatasvir/ sofosbuvir (Epclusa®), glecaprevir/pibrentasvir (Mavyret™), and sofosbuvir/velpatasvir/voxilaprevir (Vosevi®) as provided under the member’s prescription drug benefit.



      TREATMENT NAIVE

      A. Genotype 1

      Mavyret™ is approved when ALL of the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of chronic HCV genotype 1; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Not used in combination with another HCV direct acting antiviral agent; and
      5. Approved length of therapy: 56 days (8 weeks)


      Velpatasvir/ sofosbuvir (Epclusa®) is approved when ALL of the following are met:

      1. Age 3 years or older; and 
      2. Diagnosis of chronic HCV genotype 1; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Approved length of therapy: 84 days (12 weeks)*; and
      5. Inadequate response or inability to tolerate brand Epclusa® (applies to velpatasvir/sofosbuvir only), details of intolerability must be provided

      Ledipasvir/ sofosbuvir (Harvoni®) is approved when ALL of the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of chronic HCV genotype 1; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Approved length of therapy: 84 days (12 weeks)*; and
      5. Inadequate response or inability to tolerate brand Harvoni® (applies to ledipasvir/sofosbuvir only), details of intolerability must be provided

      Zepatier® is approved when ALL of the following are met:

      1. Age 12 years or older or weighing at least 30kg; and
      2. Diagnosis of HCV genotype 1; and
      3. Results of testing for baseline high fold-change NS5A resistance-associated variant are provided (for genotype 1a); and
      4. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      5. Documentation of a dispensed prescription for and inability to tolerate glecaprevir/pibrentasvir (Mavyret™), brand Harvoni® or brand Epclusa®, details of intolerability must be provided; and
      6. Used concurrently with ribavirin for genotype 1a when baseline high fold-change NS5A resistance-associated variant are detected; and
      7. Approved length of therapy:
        1. Genotype 1a without baseline high fold-change NS5A resistance-associated variant or genotype 1b: 84 days (12 weeks)*
        2. Genotype 1a with baseline high fold-change NS5A resistance-associated variant: 112 days (16 weeks)*

      Viekira Pak® is approved when ALL of the following are met:

      1. Age 18 years or older; and
      2. Diagnosis of chronic HCV genotype 1; and
      3. ONE of the following:
        1. Genotype 1a without cirrhosis; or
        2. Genotype 1b with absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Documentation of a dispensed prescription for and inability to tolerate glecaprevir/ pibrentasvir (Mavyret™), brand Harvoni® or brand Epclusa®, details of intolerability must be provided; and
      5. Used concurrently with ribavirin for genotype 1a; and
      6. Approved length of therapy: 84 days (12 weeks) *

      B. Genotype 2
      Mavyret™ is approved when all of the following are met:

      1. Age 3 years or older; and 
      2. Diagnosis of chronic HCV genotype 2; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Not used in combination with another HCV direct acting antiviral agent; and
      5. Approved length of therapy: 56 days (8 weeks)*

      Velpatasvir/ sofosbuvir (Epclusa®) is approved when ALL of the following are met: 

      1. Age 3 years or older; and 
      2. Diagnosis of chronic HCV genotype 2; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Inadequate response or inability to tolerate brand Epclusa® (applies to velpatasvir/sofosbuvir only), details of intolerability must be provided.; and
      5. Approved length of therapy: 84 days (12 weeks)*

      C. Genotype 3

      Mavyret™ is approved when ALL of the following are met:

      1. Age 3 years or older; and 
      2. Diagnosis of chronic HCV genotype 3; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Not used in combination with another HCV direct acting antiviral agent; and
      5. Approved length of therapy: 56 days (8 weeks)*

      Velpatasvir/ sofosbuvir (Epclusa®) is approved when ALL of the following are met:

      1. Age 3 years or older; and 
      2. Diagnosis of chronic HCV genotype 3; and
      3. Absence of decompensated cirrhosis (i.e. compensated cirrhosis or no cirrhosis); and
      4. Inadequate response or inability to tolerate brand Epclusa® (applies to velpatasvir/sofosbuvir only), details of intolerability must be provided.; and
      5. Concurrent use of ribavirin if compensated cirrhosis and Y93H substitution present; and
      6. Approved length of therapy: 84 days (12 weeks)

      Vosevi® is approved when ALL of the following are met:

      1. Age 18 years or older; and
      2. Diagnosis of chronic HCV genotype 3; and
      3. Compensated cirrhosis; and
      4. Presence of Y93H; and
      5. Approved length of therapy: 84 days (12 weeks)*

      D. Genotype 4 

      Mavyret™ is approved when ALL of the following are met:

      1. Age 3 years or older; and 
      2. Diagnosis of chronic HCV genotype 4; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Not used in combination with another HCV direct acting antiviral agent; and
      5. Approved length of therapy: 56 days (8 weeks)
         

      Velpatasvir/ sofosbuvir (Epclusa®) is approved when ALL of the following are met:

      1. Age 3 years or older; and 
      2. Diagnosis of chronic HCV genotype 4; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Inadequate response or inability to tolerate brand Epclusa® (applies to velpatasvir/sofosbuvir only), details of intolerability must be provided; and
      5. Approved length of therapy: 84 days (12 weeks)*

      Ledipasvir/ sofosbuvir (Harvoni®) is approved when ALL of the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of chronic HCV genotype 4; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Inadequate response or inability to tolerate brand Harvoni® (applies to ledipasvir/sofosbuvir only), details of intolerability must be provided; and
      5. Approved length of therapy: 84 days (12 weeks)*

      Zepatier® is approved when ALL of the following are met:

      1. Age 12 years or older or weighing at least 30kg; and
      2. Diagnosis of chronic HCV genotype 4; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Documentation of a dispensed prescription for and inability to tolerate glecaprevir/ pibrentasvir (Mavyret™), brand Harvoni® or brand Epclusa®, details of intolerability must be provided; and
      5. Approved length of therapy: 84 days (12 weeks)*

      E. Genotype 5 or 6
      Mavyret™ is approved when ALL of the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of chronic HCV genotype 5 or 6; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Not used in combination with another HCV direct acting antiviral agent; and
      5. Approved length of therapy: 56 days (8 weeks)

      Velpatasvir/ sofosbuvir (Epclusa®) is approved when ALL of the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of chronic HCV genotype 5 or 6; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Inadequate response or inability to tolerate brand Epclusa® (applies to velpatasvir/sofosbuvir only), details of intolerability must be provided; and
      5. Approved length of therapy: 84 days (12 weeks)*

      Ledipasvir/ sofosbuvir (Harvoni®) is approved when ALL the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of chronic HCV genotype 5 or 6; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Inadequate response or inability to tolerate brand Harvoni® (applies to ledipasvir/sofosbuvir only), details of intolerability must be provided; and
      5. Approved length of therapy: 84 days (12 weeks)*

      RETREATMENT (note: Retreatment for interferon or interferon plus first generation protease inhibitor failures should be treated as treatment naïve)

      Sofosbuvir-Based and Elbasvir/Grazoprevir Treatment Failures

      A. Genotype 1, 2, 4, 5 and 6

      Mavyret™ is approved when ALL of the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of chronic HCV genotype 1, 2, 4, 5, 6; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Member failed Sofosbuvir-Based therapy or Zepatier (Elbasvir/Grazoprevir); and
      5. Not used in combination with another HCV direct acting antiviral agent; and
      6. Approved length of therapy: 112 days (16 weeks)

      Vosevi® is approved when ALL the following are met:

      1. Age 18 years or older; and
      2. Diagnosis of chronic HCV genotype 1, 2, 4, 5, 6; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Member failed Sofosbuvir-Based therapy or Zepatier (Elbasvir/Grazoprevir); and
      5. Approved length of therapy: 84 days (12 weeks)*

      B. Genotype 3

      Vosevi® is approved when ALL the following are met:

      1. Age 18 years or older; and
      2. Diagnosis of chronic HCV genotype 3 and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Member failed Sofosbuvir-Based therapy or Zepatier (Elbasvir/Grazoprevir); and
      5. Approved length of therapy: 84 days (12 weeks)*

      Glecaprevir/Pibrentasvir Treatment Failures

      A. Genotype 1, 2, 3, 4, 5, 6

      Mavyret™ and Sovaldi® is approved when ALL of the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of chronic HCV genotype 1, 2, 3, 4, 5, 6; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Member failed Mavyret (Glecaprevir/Pibrentasvir); and
      5. Concurrent use of ribavirin; and
      6. Not used in combination with another HCV direct acting antiviral agent; and
      7. Approved length of therapy: 112 days (16 weeks)

      Vosevi® is approved when ALL the following are met:

      1. Age 18 years or older; and
      2. Diagnosis of chronic HCV genotype 1, 2, 3, 4, 5, 6; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis) ; and
      4. Member failed Mavyret (Glecaprevir/Pibrentasvir); and
      5. Approved length of therapy: 84 days (12 weeks)

      Multiple DAA Treatment Failures (All Genotypes), Including Vosevi® (Sofosbuvir/Velpatasvir/Voxilaprevir) or Sofosbuvir Plus Mavyret™ (Glecaprevir/Pibrentasvir)

      A. Genotypes 1, 2, 4, 5, 6

      Mavyret™ and Sovaldi is approved when ALL of the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of chronic HCV genotype 1, 2, 4, 5, 6; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Member failed Mavyret (Glecaprevir/Pibrentasvir) and Sovaldi (sofosbuvir) or Vosevi® (Sofosbuvir/Velpatasvir/Voxilaprevir); and
      5. Concurrent use of ribavirin; and
      6. Not used in combination with another HCV direct acting antiviral agent; and
      7. Approved length of therapy: 112 days (16 weeks)

      Vosevi® is approved when ALL the following are met:

      1. Age 18 years or older; and
      2. Diagnosis of chronic HCV genotype 1, 2, 4, 5, 6; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Member failed Mavyret (Glecaprevir/Pibrentasvir) and Sovaldi (sofosbuvir) or Vosevi® (Sofosbuvir/Velpatasvir/Voxilaprevir; and
      5. Concurrent use of ribavirin (for members with compensated cirrhosis); and
      6. Approved length of therapy: 168 days (24 weeks)

      B. Genotype 3

      Mavyret™ and Sovaldi is approved when ALL of the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of chronic HCV genotype 3; and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      4. Member failed Mavyret (Glecaprevir/Pibrentasvir) and Sovaldi (sofosbuvir) or Vosevi® (Sofosbuvir/Velpatasvir/Voxilaprevir); and
      5. Concurrent use of ribavirin; and
      6. Not used in combination with another HCV direct acting antiviral agent; and
      7. Approved length of therapy:
        1. NO cirrhosis - 112 days (16 weeks)
        2. Compensated cirrhosis up to 168 days (24 weeks)

      Vosevi® is approved when ALL the following are met:

      1. Age 18 years or older; and
      2. Diagnosis of chronic HCV genotype 3 and
      3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis) ; and
      4. Member failed Mavyret (Glecaprevir/Pibrentasvir) and Sovaldi (sofosbuvir) or Vosevi® (Sofosbuvir/Velpatasvir/Voxilaprevir); and
      5. Concurrent use of ribavirin (for members with compensated cirrhosis); and
      6. Approved length of therapy: 168 days (24 weeks)

      DECOMPENSATED CIRRHOSIS (moderate to severe hepatic impairment; Child Turcotte Pugh B or C)
      A. Treatment Naive

      Ledipasvir/ sofosbuvir (Harvoni®) is approved when ALL of the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of chronic HCV genotype 1, 4, 5, or 6; and
      3. Documentation of decompensated cirrhosis (defined as Child Turcotte Pugh class B or C) or hepatocellular carcinoma; and
      4. One of the following:
        1. Concurrent use of ribavirin; or
        2. Member is unable to tolerate ribavirin; and
      5. Prescribed by a hepatitis C expert (i.e., hepatologist, liver transplant surgeon) ; and
      6. Inadequate response or inability to tolerate brand Harvoni® (applies to ledipasvir/sofosbuvir only), details or intolerability must be provided; and
      7. Approved length of therapy:
        1. Without ribavirin: 168 days (24 weeks)*; or
        2. With ribavirin: 84 days (12 weeks)*

      Velpatasvir/sofosbuvir (Epclusa®) is approved when ALL of the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of chronic HCV genotype 1, 2, 3, 4, 5, or 6; and
      3. Documentation of decompensated cirrhosis (defined as Child Turcotte Pugh class B or C) or hepatocellular carcinoma; and
      4. One of the following:
        1. Concurrent use of ribavirin; or
        2. Member is unable to tolerate ribavirin; and
      5. Prescribed by a hepatitis C expert (i.e., hepatologist, liver transplant surgeon) ; and
      6. Inadequate response or inability to tolerate brand Epclusa® (applies to velpatasvir/sofosbuvir only), details of intolerability must be provided; and
      7. Approved length of therapy:
        1. With ribavirin: 168 days (24 weeks)*; or
        2. Without ribavirin: 168 days (24 weeks)*

      B. Retreatment with Prior Sofosbuvir or NS5A inhibitor-base treatment

      Ledipasvir/ sofosbuvir (Harvoni®) is approved when ALL of the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of chronic HCV genotype 1, 4, 5, or 6; and
      3. Documentation of decompensated cirrhosis (defined as Child Turcotte Pugh class B or C) or hepatocellular carcinoma; and
      4. Prescribed by a hepatitis C expert (i.e., hepatologist, liver transplant surgeon); and
      5. Concurrent use of ribavirin; and
      6. Inadequate response or inability to tolerate brand Harvoni® (applies to ledipasvir/sofosbuvir only), details or intolerability must be provided; and
      7. Approved length of therapy: 168 days (24 weeks)*

      Velpatasvir/sofosbuvir (Epclusa®) is approved when ALL of the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of chronic HCV genotype 1, 2, 3, 4, 5, or 6; and
      3. Documentation of decompensated cirrhosis (defined as Child Turcotte Pugh class B or C) or hepatocellular carcinoma; and
      4. Prescribed by a hepatitis C expert (i.e., hepatologist, liver transplant surgeon) ; and
      5. Concurrent use of ribavirin; and
      6. Inadequate response or inability to tolerate brand Epclusa® (applies to velpatasvir/sofosbuvir only) details of intolerability must be provided; and
      7. Approved length of therapy: 168 days (24 weeks)*


      RECURRENT HCV POST LIVER TRANSPLANT

      Genotype 1

      Mavyret™ is approved when there is documentation of ALL of the following:

      1. Age 3 years or older; and 
      2. Diagnosis of HCV genotype 1; and
      3. Documentation of liver transplant; and
      4. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      5. Not used in combination with another HCV direct acting antiviral agent; and
      6. Approved length of therapy: 84 days (12 weeks)*

      Ledipasvir/ sofosbuvir (Harvoni®) is approved when there is documentation of ALL of the following:

      1. Age 3 years or older; and
      2. Diagnosis of HCV genotype 1; and
      3. Documentation of liver transplant; and
      4. Used with ribavirin; and
      5. Inadequate response or inability to tolerate brand Harvoni® (applies to ledipasvir/sofosbuvir only), details of intolerability must be provided; and
      6. Approved length of therapy: 84 days (12 weeks)*

      Viekira Pak® is approved when ALL of the following are met:

      1. Age 18 years or older; and
      2. Diagnosis of HCV genotype 1; and
      3. Documentation of liver transplant; and
      4. Documentation of normal hepatic function; and
      5. Documentation of mild fibrosis; and
      6. Used with ribavirin; and
      7. Documentation of a dispensed prescription for and inability to tolerate glecaprevir/ pibrentasvir (Mavyret™) or brand Harvoni®, details of intolerability must be provided; and
      8. Approval length: 24 weeks

      B. Genotype 2 or 3

      Mavyret™ is approved when ALL of the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of HCV genotype 2 or 3; and
      3. Documentation of liver transplant; and
      4. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      5. Not used in combination with another HCV direct acting antiviral agent; and
      6. Approved length of therapy: 84 days (12 weeks)*

      Velpatasvir/ sofosbuvir (Epclusa®) is approved when ALL the following are met:

      1. Age 3 years or older; and
      2. Diagnosis of HCV genotype 2 or 3; and
      3. Documentation of liver transplant; and
      4. Used with ribavirin; and
      5. Presence of cirrhosis; and
      6. Inadequate response or inability to tolerate brand Epclusa® (applies to velpatasvir/sofosbuvir only), details of intolerability must be provided; and
      7. Approved length of therapy: 84 days (12 weeks)*

      C. Genotype 4, 5 or 6

      Mavyret™ is approved when there is documentation of ALL of the following:

      1. Age 3 years or older; and
      2. Diagnosis of HCV genotype 4, 5, or 6; and
      3. Documentation of liver transplant; and
      4. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      5. Not used in combination with another HCV direct acting antiviral agent; and
      6. Approved length of therapy: 84 days (12 weeks)*

      Ledipasvir/ sofosbuvir (Harvoni®) is approved when there is documentation of ALL of the following:

      1. Age 3 years or older; and
      2. Diagnosis of HCV genotype 4, 5, or 6; and
      3. Documentation of liver transplant; and
      4. Used with ribavirin; and
      5. Inadequate response or inability to tolerate brand Harvoni® (applies to ledipasvir/sofosbuvir only), details of intolerability must be provided; and
      6. Approved length of therapy: 84 days (12 weeks)*

      KIDNEY TRANSPLANT RECIPIENT
      A.    Genotype 1 or 4
      Mavyret™ is approved when there is documentation of ALL of the following:

      1. Age 3 years or older ; and
      2. Diagnosis of HCV genotype 1 or 4; and
      3. Documentation of kidney transplant; and
      4. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      5. Not used in combination with another HCV direct acting antiviral agent; and
      6. Approved length of therapy: 84 days (12 weeks)*  

      Ledipasvir/ sofosbuvir (Harvoni®) is approved when there is documentation of ALL of the following:

      1. Age 3 years or older; and
      2. Diagnosis of HCV genotype 1 or 4; and
      3. Documentation of kidney transplant; and
      4. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      5. Inadequate response or inability to tolerate brand Harvoni® (applies to ledipasvir/sofosbuvir only), details of intolerability must be provided; and
      6. Approved length of therapy: 84 days (12 weeks)*

      B. Genotype 2,3,5, or 6
      Mavyret™ is approved when there is documentation of ALL of the following:

      1. Age 3 years or older; and
      2. Diagnosis of HCV genotype 2,3,5, or 6; and
      3. Documentation of kidney transplant; and
      4. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
      5. Not used in combination with another HCV direct acting antiviral agent; and
      6. Approved length of therapy: 84 days (12 weeks)*

      *Approved length of therapy: if therapy was initiated prior to coverage with the plan, authorization will only be granted to allow completion of the specified therapy.  Authorizations will end 180 days after receipt of request.

      Maximum doses per day apply

       

      DrugMaximum dose per day (tablets)
      velpatasvir/ sofosbuvir (Epclusa®)1
      velpatasvir/ sofosbuvir (Epclusa®) pack 200-50mg2
      velpatasvir/ sofosbuvir (Epclusa®) pack 150-37.5mg1
      Mavyret™3
      Mavyret™ pak 50-20mg5
      Ledipasvir/sofosbuvir (Harvoni®)1

      Sovaldi® 1
      Viekira Pak®6
      Zepatier®1
      Vosevi®1

       

      HCV Treatment Regimens that are not recommended and considered not medically necessary

      1. Sofosbuvir with ribavirin x 24 weeks (except in genotype 2 post liver transplant)
      2. Peg-interferon and ribavirin with or without sofosbuvir, simeprevir, telaprevir, or boceprevir)
      3. Monotherapy with peg-interferon, ribavirin, or a direct-acting antiviral
      4. Simeprevir, paritaprevir, or elbasvir/grazoprevir based regimens in those decompensated cirrhosis

      Epclusa® (velpatasvir/sofosbuvir), Sovaldi® (sofosbuvir), Viekira Pak® (ombitasvir/paritaprevir/ritonavir/dasabuvir), Harvoni® (ledipasvir/sofosbuvir),  Zepatier® (elbasvir/grazoprevir), Mavyret™ (glecaprevir and pivrentasvir) & Vosevi® (sofosbuvir/velpatasvir/voxilaprevir):

      RISK OF HEPATITIS B REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV:
      Hepatitis B virus (HBV) reactivation has been reported, in some cases resulting in fulminant hepatitis, hepatic failure, and death. 

      American Association for the Study of Liver Disease, Infectious Diseases Society or America, International Antiviral Society-USA. Recommendations for testing, managing and treating Hepatitis C. Available from https://www.hcvguidelines.org/.  Accessed July 31, 2024.

      Epclusa® (velpatasvir/sofosbuvir) [package insert]. Forest City, CA: Gilead Sciences, Inc; May, 2022. Available from: https://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/epclusa/epclusa_pi.pdf. Accessed July 31, 2024.

      Harvoni® (ledipasvir/sofosbuvir) [package insert]. Forest City, CA: Gilead Sciences, Inc; March 2020. Available from: https://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/harvoni/harvoni_pi.pdf. Accessed July 31, 2024.

      Hepatitis C Information for Health Professionals. Centers for Disease Control and Prevention. July 2019. Available from: http://www.cdc.gov/hepatitis/HCV/HCVfaq.htm. Accessed July 31, 2024.

      Mavyret™ (glecaprevir/pibrentasvir) [package insert]. North Chicago, IL: AbbVie, Inc.; June 2021. Available from https://www.rxabbvie.com/pdf/mavyret_pi.pdf. Accessed July 31, 2024.

      Sovaldi® (sofosbuvir) [package insert]. Forest City, CA: Gilead Sciences, Inc; April 2021. Available from: https://www.gilead.com/~/media/files/pdfs/medicines/liver-disease/sovaldi/sovaldi_pi.pdf?evo_source=SOVALDI. Accessed July 31, 2024.

      Viekira Pak® (ombitasvir/ paritaprevir/ ritonavir and dasabuvir) [package insert]. North Chicago, IL: AbbVie, Inc; Nov 2020. Available from: https://www.rxabbvie.com/pdf/viekirapak_pi.pdf. Accessed July 31, 2024.

      Vosevi™ (sofosbuvir/velpatasvir/voxilaprevir) [package insert]. Foster City, CA: Gilead Sciences, Inc.; November 2019. Available from: http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/vosevi/vosevi_pi.pdf. Accessed July 31, 2024.

      Zepatier® (elbasvir/ grazeprovir) [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; May 2022. Available from: https://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_pi.pdf. Accessed July 31, 2024.

      		297/1/20246/6/202510/1/2024 1:14 AMNo presence informationsrv_ppsgw_P
      Off-label Drug Use Rx.01.33​
      Brand NameGeneric Name
      Epclusa®velpatasvir/ sofosbuvir
      Harvoni®ledipasvir/ sofosbuvir
      Viekira Pak®
      		ombitasvir/ paritaprevir/ ritonavir and dasabuvir
      Sovaldi®
      		sofosbuvir
      Zepatier®
      		elbasvir/grazoprevir
      ​MavyretTM

      		​glecaprevir/pibrentasvir 
      ​Vosevi®
      		​sofosbuvir/velpatasvir/voxilaprevir 
         
      		Zepatier®, Harvoni®, Viekira Pak®, Sovaldi®, Epclusa®, Mavyret™, Vosevi®elbasvir/ grazeprevir, ledipasvir/ sofosbuvir, ombitasvir/ paritaprevir/ ritonavir and dasabuvir, sofosbuvir, velpatasvir/ sofosbuvir, glecaprevir/pibrentasvir, sofosbuvir/velpatasvir/voxilaprevir
      454
        
      		10/1/2024Rx.01.109CommercialOyenusi, OluwadamilolaQ2-2024

      Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of angioedema. The most frequently implicated areas during an attack of HAE include areas of the skin, gastrointestinal tract, and upper respiratory tract, including the larynx. Involvement of the larynx may lead to fatality by asphyxiation. During episodes of HAE, individuals experience severe edema of the affected areas, characterized by gradual worsening over 24 hours and resolution within 2-5 days without treatment. Importantly, symptoms of HAE exclude urticaria and pruritis.

      Several forms of hereditary angioedema exist, with type I and II being most common. In most cases, individuals with HAE demonstrate a deficiency in C1 inhibitor caused by mutation in the C1 inhibitor gene. .

      Neither anabolic steroids nor antifibrinolytic drugs, used for prophylaxis of HAE attacks, are reliably effective in treating acute HAE attacks.  Epinephrine, corticosteroids, and antihistamines are also not effective for treating HAE attacks and are not recommended by current guidelines.  Guidelines recommend that patients with HAE have access to an "effective, on-demand, HAE-specific agent" to manage acute attacks. 

      Mechanism of Action

      Vasodilation results from excessive bradykinin production, a downstream effect from a deficiency in C1 (a subset of Complement protein) inhibitor protein. C1-inhibitor protein inhibits kallikrein, which is a protease that activates the potent vasodilator, bradykinin.  Modulation of the C1 cascade is a target for the prophylaxis and treatment of acute attacks of HAE.   Patients with HAE have low levels of endogenous or functional C1 esterase inhibitor (C1INH). Although the events that induce attacks of angioedema in HAE patients are not well understood, it is thought that contact system activation occurs. Contact system activation results in increased levels of bradykinin which causes increases in vascular permeability which results in the clinical manifestations of HAE.

      Sajazir™/Firazyr® (icatibant) inhibits bradykinin from binding the B2 receptor and thereby treats the clinical symptoms of an acute, episodic attack of hereditary angioedema.  Icatibant is a bradykinin B2 receptor antagonist indicated for treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older.   

      Haegarda® (C1 esterase inhibitor subcutaneous [human]) is a plasma-derived concentrate of C1 esterase inhibitor (human) that is indicated for routine prophylaxis to prevent HAE attacks in patients 6 years of age and older. 

      Cinryze® (C1 esterase inhibitor [human]) is C1 esterase inhibitor indicated for routine prophylaxis against angioedema attacks in pediatric (6 years old and above), adolescent and adult patients with HAE.

      Berinert® (C1 esterase inhibitor [human] is a plasma-derived C1 esterase inhibitor (human) indicated for the treatment of acute abdominal, facial, or laryngeal HAE attacks in adult and pediatric patients.

      Orladeyo™ (berotralstat) is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older.

      Ruconest® is a C1 esterase inhibitor [recombinant] indicated for the treatment of acute attacks in adults and adolescent patients with HAE.

      Takhzyro® (lanadelumab-flyo) is a human monoclonal antibody that acts to inhibit plasma kallikrein, and is indicated for prevention of HAE in patients 2 years of age and older. Kallikrein is a protease that activates bradykinin, a potent vasodilator implicated in the pathogenesis of angioedema attacks in patients with HAE. Inhibition of kallikrein results in downstream inhibition of bradykinin production.


      The intent of this policy is to communicate the medical necessity criteria for Takhzyro® (lanadelumab-flyo), Haegarda® (C1 esterase inhibitor subcutaneous [human]), Cinryze® (C1 esterase inhibitor [human]), Berinert® (C1 esterase inhibitor [human]), Ruconest® (C1 inhibitor recombinant), Sajazir™/Firazyr® (icatibant), and Orladeyo™ (berotralstat) as provided under the member's pharmacy benefit. 



      Prophylaxis against angioedema attacks

      INITIAL CRITERIA: C1 esterase inhibitor (human) (Cinryze® or Haegarda®) is approved when ALL of the following are met:

      1. Diagnosis of hereditary angioedema (HAE); and
      2. One of the following:
        1. Diagnosis has been confirmed by C1 inhibitor (C1-INH) deficiency or dysfunction (Type I or II HAE) as documented by one of the following:

                                    i.      C1-INH antigenic level below the lower limit of normal; or

                                    ii.      C1-INH functional level below the lower limit of normal; or

        1. Diagnosis has been confirmed by both of the following:

                                     i.      Member has normal C1-INH level (HAE-n1-C1INH previously referred to as HAE Type 3); and

                                     ii.      One of the following:

            1. Confirmed presence of a FXII, plasminogen gene mutation, angiopoietin-1 mutation, or kininogen mutation; or
            2. Member has recurrent angioedema attacks that are refractory to high-dose antihistamines (e.g., cetirizine) with a confirmed family history of recurrent angioedema; and

      1. Prescribed by or in consultation with an immunologist, allergist, or pulmonologist; and
      2. Member is 6 years of age or greater; and
      3. For prophylaxis against HAE attacks; and
      4. For Cinryze only, inadequate response or inability to tolerate ONE of the following:
        1. Haegarda; or
        2. Takhzyro; or
        3. Orladeyo

      Initial authorization duration: 2 years
       
      REAUTHORIZATION CRITERIA CI esterase inhibitors (human) (Cinryze® or Haegarda®) is re-approved with documentation of positive clinical response to therapy.

      Reauthorization duration: 2 years

      INITIAL CRITERIA: Lanadelumab-flyo (Takhzyro®) injection or berotralstat (Orladeyo®) is approved when all of the following are met:

      1. Diagnosis of hereditary angioedema (HAE); and
      1. One of the following:
        1. Diagnosis has been confirmed by C1 inhibitor (C1-INH) deficiency or dysfunction (Type I or II HAE) as documented by one of the following:

                                   i.      C1-INH antigenic level below the lower limit of normal; or

                                   ii.      C1-INH functional level below the lower limit of normal; or

        1. Diagnosis has been confirmed by both of the following:

                                    i.      Member has normal C1-INH level (HAE-n1-C1INH previously referred to as HAE Type 3); and

                                   ii. One of the following:

            1. Confirmed presence of a FXII, plasminogen gene mutation, angiopoietin-1 mutation, or kininogen mutation; or
            2. Member has recurrent angioedema attacks that are refractory to high-dose antihistamines (e.g., cetirizine) with a confirmed family history of recurrent angioedema; and
      1. For prophylaxis against HAE attacks; and
      2. One of the following:
        1. For Takhzyro, member is 2 years of age or older; or
        2. For Orladeyo, member is 12 years of age or older; and
      3. Prescribed by or in consultation with an immunologist, allergist, or pulmonologist

      Initial authorization duration: 2 years

      REAUTHORIZATION CRITERIA: Lanadelumab-flyo (Takhzyro®), or berotralstat (Orladeyo®) is re-approved with documentation of positive clinical response to therapy.

      Reauthorization duration: 2 years

      __________________________________________________________________________________________

      Treatment of angioedema attacks

      INITIAL CRITERIA: C1 esterase inhibitor (human) (Berinert®) is approved when ALL of the following are met:

      1. Diagnosis of hereditary angioedema (HAE); and
      2. One of the following:
        1. Diagnosis has been confirmed by C1 inhibitor (C1-INH) deficiency or dysfunction (Type I or II HAE) as documented by one of the following:

                                    i.      C1-INH antigenic level below the lower limit of normal; or

                                    ii.      C1-INH functional level below the lower limit of normal; or

        1. Diagnosis has been confirmed by both of the following:

                                    i.      Member has normal C1-INH level (HAE-n1-C1INH previously referred to as HAE Type 3); and

                                    ii.      One of the following:

            1. Confirmed presence of a FXII, plasminogen gene mutation, angiopoietin-1 mutation, or kininogen mutation; or
            2. Member has recurrent angioedema attacks that are refractory to high-dose antihistamines (e.g., cetirizine) with a confirmed family history of recurrent angioedema; and
      1. Prescribed by or in consultation with an immunologist, allergist, or pulmonologist; and
      2. For the treatment of acute abdominal, facial, or laryngeal HAE attacks; and
      3. One of the following:
        1. Inadequate response or inability to tolerate C1 esterase inhibitor recombinant (Ruconest®); or
        2. One of the following:

                                    i. Member is 12 years of age or younger; or

                                   ii. Documentation that member has history of laryngeal attacks

      Initial authorization duration: 2 years

      REAUTHORIZATION CRITERIA: C1 esterase inhibitors (human) (Berinert®) is re-approved with documentation of positive clinical response to therapy.

      Reauthorization duration: 2 years

      INITIAL CRITERIA: C1 esterase inhibitor recombinant (Ruconest®) is approved when ALL of the following are met:

      1. Diagnosis of hereditary angioedema (HAE); and

      2. One of the following:

      a. Diagnosis has been confirmed by C1 inhibitor (C1-INH) deficiency or dysfunction (Type I or II HAE) as documented by one of the following:

                               i.      C1-INH antigenic level below the lower limit of normal; or

                               ii.      C1-INH functional level below the lower limit of normal; or

                   b. Diagnosis has been confirmed by both of the following:

                                i.      Member has normal C1-INH level (HAE-n1-C1INH previously referred to as HAE Type 3); and

                                ii.      One of the following:

              1. Confirmed presence of a FXII, plasminogen gene mutation, angiopoietin-1 mutation, or kininogen mutation; or
              2. Member has recurrent angioedema attacks that are refractory to high-dose antihistamines (e.g., cetirizine) with a confirmed family history of recurrent angioedema; and
        1. Prescribed by or in consultation with an immunologist, allergist, or pulmonologist; and
        2. Member is 13 years of age or older; and
        3. For the treatment of acute HAE attacks

        Initial authorization duration: 2 years

        REAUTHORIZATION CRITERIA: C1 esterase inhibitor recombinant (Ruconest®) is re-approved with documentation of positive clinical response to therapy

        Reauthorization duration: 2 years

        INITIAL CRITERIA: Icatibant (Firazyr® /Sajazir™) is approved when ALL of the following are met:

        1. Member is 18 years of age or older; and

        2. Diagnosis of hereditary angioedema; and

        3. One of the following:

                   a. Diagnosis has been confirmed by C1 inhibitor (C1-INH) deficiency or dysfunction (Type I or II HAE) as documented by one of the following:

                                 i.      C1-INH antigenic level below the lower limit of normal; or

                                 ii.      C1-INH functional level below the lower limit of normal; or

                     b. Diagnosis has been confirmed by both of the following:

                                  i.      Member has normal C1-INH level (HAE-n1-C1INH previously referred to as HAE Type 3); and

                                  ii.      One of the following:

                1. Confirmed presence of a FXII, plasminogen gene mutation, angiopoietin-1 mutation, or kininogen mutation; or
                2. Member has recurrent angioedema attacks that are refractory to high-dose antihistamines (e.g., cetirizine) with a confirmed family history of recurrent angioedema; and
          1. For the treatment of acute HAE attacks; and
          2. Prescribed by or in consultation with an immunologist, allergist, or pulmonologist

          Initial authorization duration: 2 years

          REAUTHORIZATION CRITERIA Icatibant (Firazyr®/Sajazir™) is re-approved with documentation of positive clinical response to therapy.

          Reauthorization duration: 2 years


          None

          Firazyr® (icatibant) [package insert]. Lexinton MA. Shire Orphan Therapeutics. Oct, 2021  Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=ed6657ca-ab68-477a-9968-e12dc928b540&type=display. Accessed August 4, 2024

          Zuraw BL, Bernstein JA, Lang DM, et al. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema.  J Allergy Clin Immunol. 2013; Volume 131, issue 6, pages 1491-1493.e25. Accessed August 4, 2024.

          Haegarda® (C1 esterase inhibitor subcutaneous [human]). [package insert]. Kanakee, IL: CSL Behring. January 2022. Available at: http://labeling.cslbehring.com/PI/US/HAEGARDA/EN/HAEGARDA-Prescribing-Information.pdf. Accessed August 4, 2024.

          Cinryze® (C1 esterase inhibitor [human]). [package insert]. Lexington, MA: Shire ViroPharma Inc. January 2021. Available at: http://pi.shirecontent.com/PI/PDFs/Cinryze_USA_ENG.pdf. Accessed August 4, 2024.

          Berinert® (C1 esterase inhibitor [human]). [package insert]. Kanakee, IL: CSL Behring. September 2021. Available at: http://labeling.cslbehring.com/PI/US/Berinert/EN/Berinert-Prescribing-Information.pdf. Accessed August 4, 2024

          Orladeyo™ (berotralstat). [prescribing information]. Durham, NC: BioCryst Pharmaceuticals, Inc. March 2022. Available at: https://orladeyohcp.com/wp-content/uploads/ORLADEYO_PI_V1_2020.pdf. Accessed August 4, 2024.  

          Ruconest® (C1 esterase inhibitor [recombinant]). [package insert]. Raleigh, NC: Santarus, Inc. April 2020. Available at: https://www.ruconest.com/PDF/ruconest-pi.pdf. Accessed August 4, 2024

          Sajazir™ (icatibant) [package insert]. Cambridge, United Kingdom. Cycle Pharmaceuticals Ltd. June 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1756aca0-21a1-4898-8d6c-9666738db45c. Accessed August 4, 2024

          Takhzyro®. [package insert]. Lexington, MA: Dyax Corp., wholly-owned subsidiary of Shire US Inc. February 2023. Available at: https://www.shirecontent.com/PI/PDFs/TAKHZYRO_USA_ENG.pdf. Accessed August 4, 2024.

          Zuraw B MD, Farkas H MD. Hereditary angioedema (due to C1 inhibitor deficiency): Pathogenesis and diagnosi. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. Accessed on August 4, 2024


          		217/1/20246/6/202510/1/2024 1:14 AMNo presence informationsrv_ppsgw_P

          Rx.01.33 Off Label Use

          ​Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit


          Brand NameGeneric Name
          Firazyr®/Sajazir™icatibant
          Haegarda®C1 esterase inhibitor subcutaneous [human]
          Cinryze®
          		C1 esterase inhibitor [human]
          Berinert®C1 esterase inhibitor [human]
          Orladeyo™

          berotralstat

           

          Ruconest®C1 esterase inhibitor [recombinant]
          Takhzyro®lanadelumab-flyo

          		NANA
          455
            
          		10/1/2024Rx.01.228CommercialOyenusi, OluwadamilolaQ2-2024

          Elevated triglyceride levels are associated with and appear to be implicated in the pathogenesis of atherosclerosis and cardiovascular disease (CVD). Atherosclerosis is the most common underlying pathology in patients with CVD. Fasting plasma triglyceride concentrations may be categorized according to the National Cholesterol Education Program (NCEP) as normal (<150 mg/dL), borderline (150–199 mg/dL), high triglyceride (HTG; 200–499 mg/dL), and severe HTG (HTG; ≥500 mg/dL). Patients with triglycerides above 500 mg/dL are also at risk of pancreatitis. Elevated plasma triglyceride concentrations contribute to increased risk of cardiovascular disease, both directly and because such elevations are associated with risk factors such as obesity, metabolic syndrome, and type 2 diabetes mellitus. Diet and lifestyle changes along with treatment or elimination of secondary causes are recommended before direct pharmacotherapy. If these changes are not possible or not effective, initiating triglyceride-lowering pharmacotherapy may be required.

          Vascepa® (icosapent ethyl) is indicated:

          1. As an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with elevated triglyceride (TG) levels (≥ 150 mg/dL) and
            1. Established cardiovascular disease or
            2. Diabetes mellitus and 2 or more additional risk factors for cardiovascular disease.
          2. As an adjunct to diet to reduce TG levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia.

           

          The mechanisms of action contributing to reduction of cardiovascular events with Vascepa® (icosapent ethyl) are not completely understood but are likely multi-factorial. Increased omega-3 fatty acid eicosapentaenoic acid (EPA) lipid composition from carotid plaque specimens and increased circulating EPA/arachidonic acid ratio have been observed following EPA treatment. EPA inhibits platelet aggregation under some ex vivo conditions. However, the direct clinical meaning of individual findings is not clear.


          ​The intent of this policy is to communicate the medical necessity criteria for icosapent ethyl (Vascepa®) as provided under the member's prescription drug benefit.

          Severe Hypertriglyceridemia

          INITIAL CRITERIA: Icosapent ethyl (Vascepa®) is approved when ALL of the following are met:

          1. Diagnosis of severe hypertriglyceridemia defined as pre-treatment triglyceride level greater than or equal to 500 mg/dl; and
          2. Member is 18 years of age or older; and  
          3. Medication will be used adjunct to an appropriate lipid-lowering diet; and
          4. Member has an inadequate response or inability to tolerate omega-3-acid ethyl esters (generic Lovaza®); and
          5. For Brand Vascepa® only, inadequate response or inability to tolerate generic Icosapent ethyl capsules

          Initial authorization duration: 6 Months

           

          REAUTHORIZATION CRITERIA: Icosapent ethyl (Vascepa®) is approved when ALL of the following are met:

          1. Documentation of positive clinical response to therapy; and
          2. Member continues to use the medication adjunct to an appropriate lipid-lowering diet

           

          Reauthorization duration: 2 years

          ________________________________________________________________________________________

          Hypertriglyceridemia—Reduction of risk of cardiovascular events

          INITIAL CRITERIA Icosapent ethyl (Vascepa®) is approved when ALL of the following are met:

          1. Diagnosis of hypertriglyceridemia; and
          2. Member is 18 years of age or older; and  
          3. Member has pre-treatment triglyceride level between 150 mg/dL to 499 mg/dL; and
          4. ONE of the following: 
            1. Member has established cardiovascular disease; or
            2. Both of the following:
              1. Diagnosis of diabetes mellitus; and
              2. Member has 2 or more additional risk factors for cardiovascular disease (e.g., cigarette smoking, hypertension, creatinine clearance less than 60 ml/min, etc.); and
          1. One of the following:
            1. Member has been receiving 12 consecutive weeks of statin therapy at maximally tolerated dose and will continue to receive statin therapy at maximally tolerated dose; or
            2. Inability to tolerate statin therapy; and
          2. For Brand Vascepa® only, inadequate response or inability to tolerate generic Icosapent ethyl capsules


          Initial authorization duration: 6 months

          REAUTHORIZATION CRITERIA Icosapent ethyl (Vascepa®) is re-approved when BOTH of the following are met:

          1. Documentation of positive clinical response to therapy; and
          2. One of the following:
            1. Member continues to receive statin therapy at maximally tolerated dose; or
            2. Inability to tolerate statin therapy
               

          Reauthorization duration: 2 years


          N/A

          Skulas-Ray AC, Wilson PWF, Harris WS et al on behalf of the American Heart Association. Omega-3 fatty acids for the management of hypertriglyceridemia. Circulation. 2019;140. Accessed August 4, 2024

          Vascepa® (icosapent ethyl) [prescribing information]. Bridgewater, NJ: Amarin Pharma, Inc.; September 2021. Available from: https://amarincorp.com/docs/Vascepa-PI.pdf. Accessed August 4, 2024

          Yuan, G, Al-Shali, KZ, Hegele, RA. Hypertriglyceridemia: its etiology, effects and treatment. CMAJ. 2007;176:1113–1120. doi: 10.1503/cmaj.060963. Accessed August 4, 2024




          		67/1/20246/6/202510/1/2024 1:15 AMNo presence informationsrv_ppsgw_P
          Off-Label Use Rx.01.33​
          Brand nameGeneric name
          Vascepa®Icosapent ethyl

          		NANA
          456
            
          		10/1/2024Rx.01.184CommercialOyenusi, OluwadamilolaQ2-2024
          An interim clinical policy is the written description of the plan’s utilization management position concerning the use or application of a new or recently introduced product that is covered under the pharmacy benefit. These policies are implemented prior to review by the Pharmacy and Therapeutics Committee. Criteria are based on an initial clinical review performed by Clinical Pharmacy Services. The intent of the interim policy is to provide a means to manage newly approved products while allowing sufficient time for a thorough clinical review and evaluation by the Pharmacy and Therapeutics Committee. The product to which an interim clinical policy applies is considered medically necessary when requested for an indication approved by the Food and Drug Administration and, when available, there is inadequate response or inability to tolerate one generic alternative and one preferred brand with the same indication. The policy is effective as of the date of market entry.  A clinical policy, if issued, will be available when approved by the Pharmacy and Therapeutics Committee within 180 days of the drug market entry, designated by the Medispan release date. If a clinical policy is not approved within 180 days, the interim clinical policy will be retired. Interim clinical policy will remain in effect until the clinical policy effective date.
          ​The intent of this policy is to communicate the medical necessity criteria for new or recently introduced products as provided under the member’s prescription drug benefit.

          A new or recently introduced product is approved when both of the following are met:

          1. Diagnosis of an FDA approved, or compendia supported, indication; and
          2. Inadequate response or inability to tolerate BOTH of the following (when available):
            1. One generic alternative with the same indication; and
            2. One preferred brand with the same indication

          Authorization duration: 1 year

          A new authorized generic/authorized brand alternative is approved when all of the following are met:

          1. Diagnosis of an FDA approved, or compendia supported, indication; and
          2. Submission of documentation (e.g., chart note) or claim history showing at least 3 months of use of the brand product within the previous 365 days; and
          3. Submission of documentation (e.g., chart note) confirming BOTH of the following:
            1. The brand product has not been effective; and
            2. Justification for why the target drug is expected to provide benefit when the brand product has not been shown to be effective

          Authorized duration: 1 year


          None
          None
          		97/1/20246/6/202510/1/2024 1:15 AMNo presence informationsrv_ppsgw_P
          ​Off-Label Use Rx. 01.33
          Applicable drugs will vary as new products are released to market.
          		NANA
          457
            
          		10/1/2024Rx.01.265CommercialOyenusi, OluwadamilolaQ2-2024
          The intent of this policy is to communicate the medical necessity criteria for Mavacamten (Camzyos™) as provided under the member's prescription drug benefit.

          ​Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease characterized by hypertrophy of a nondilated left ventricle in the absence of any other cardiac or systemic disease (such as hypertension) that could account for observed hypertrophy, microvascular dysfunction and myocardial fibrosis. Histopathological features include myofiber disarray and myocardial fibrosis resulting from microvascular ischemia and cell death. HCM is caused largely by mutations in genes encoding thick and thin contractile myofilament proteins of the cardiac sarcomere. Phenotypically, HCM can be obstructive (70% of patients), with presence of left ventricular outflow tract obstruction, or nonobstructive (30% of patients). Complications include syncope, heart failure, and sudden death.


          Mavacamten is an allosteric and reversible inhibitor selective for cardiac myosin. Mavacamten modulates the number of myosin heads that can enter “on actin” (power-generating) states, thus reducing the probability of force-producing (systolic) and residual (diastolic) cross-bridge formation. Excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state are mechanistic hallmarks of HCM. Mavacamten shifts the overall myosin population towards an energy-sparing, recruitable, super-relaxed state. In HCM patients, myosin inhibition with mavacamten reduces dynamic left ventricular outflow tract (LVOT) obstruction and improves cardiac filling pressures.

          Mavacamten is indicated for treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms.

          INITIAL CRITERIA: Mavacamten (Camzyos™) is approved when ALL of the following are met:

           

          1. Submission of medical records (e.g., chart notes, lab values) confirming a diagnosis of symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM); and 
          2. Members is 18 years of age or older; and 
          3. Member's baseline left ventricular ejection fraction (LVEF) is greater than or equal to 55%; and 
          4. Member has Valsalva left ventricular outflow tract (LVOT) peak gradient greater than or equal to 50 mmHg at rest or with provocation; and
          5. Inadequate response or inability to tolerate BOTH of the following at a maximally tolerated dose:
            1. Non-vasodilating One beta blocker (e.g., bisoprolol, propranolol); and
            2. Calcium channel blocker (e.g., verapamil, diltiazem); and
          6. Prescribed by or in consultation with a cardiologist


          Initial authorization duration: 6 months

           

          REAUTHORIZATION CRITERIA: Mavacamten (Camzyos™) is re-approved when ALL of the following are met:

           

          1. Documentation of positive clinical response to therapy (e.g., improved symptom relief); and
          2. Member's left ventricular ejection fraction (LVEF) is greater than or equal to 50%; and
          3. Prescribed by or in consultation with a cardiologist.

           

          Reauthorization duration: 12 months


          Risk of Heart Failure

          • CAMZYOS can cause heart failure due to systolic dysfunction.
          • Echocardiogram assessments of left ventricular ejection fraction (LVEF) required before and during CAMZYOS use.
          • Initiation in patients with LVEF <55% not recommended. Interrupt if LVEF <50% or if worsening clinical status.
          • Certain CYP450 inhibitors and inducers are contraindicated in patients taking CAMZYOS because of an increased risk of heart failure.

          CAMZYOS is available only through a restricted program called the CAMZYOS REMS Program.


          DynaMed. Hypertrophic Cardiomyopathy. EBSCO Information Services. https://www.dynamed.com/condition/hypertrophic-cardiomyopathy. Accessed August 4, 2024

           

          Camzyos™ (mavacamten) [prescribing information]. Brisbane, CA: MyoKardia, Inc.; June 2023. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214998s000lbl.pdf. Accessed August 4, 2024


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          ​Rx.01.33 Off Label Use

          Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit


          Brand NameGeneric Name
          CamzyosTMMavacamten

          		N/AN/A
          458
            
          		10/1/2024Rx.04.6Claim Payment PolicyOyenusi, OluwadamilolaQ2-2024
          ​Injectable drugs indicated for administration by a healthcare professional are covered under the medical benefit.  There are times when an exception is requested to cover such drugs under the member's prescription drug benefit where they are otherwise excluded.
          The intent of this policy is to describe circumstances when injectable medications typically covered under the medical benefit may be covered under the member’s prescription drug benefit.

          Coverage is subject to the terms, conditions, and limitations of the member's contract.

          The following medications are covered under the medical benefit:

          1. Cyanocobalamin (vitamin B12) injection
          2. Heparin injection
          3. Hydrocortisone injection
          4. Methotrexate injection (vial)
          5. Non-insulin syringes/needles

           

          A benefit exception will be made to cover cyanocobalamin injection, heparin injection, hydrocortisone injection, methotrexate vials under the prescription drug benefit when ALL of the following are met:

          1. The requested drug is being used for a Food and Drug Administration approved indication or compendium supported indication as outlined in Off-label Use policy; and
          2. The prescriber assumes responsibility for teaching the member proper preparation, administration and disposal; and
          3. The prescriber provides a statement indicating the reason prescription drug benefit products are not an option, and
          4. ONE of the following:
            1. Provider does not stock the requested medication; or
            2. Access at the provider's office is not feasible due to frequency of administration

          A benefit exception will be made to cover non-insulin syringes/needles under the prescription drug benefit when required to administer an injectable medication and not supplied with the product.

          Coverage is subject to the terms of the member's prescription drug benefit, including but not limited to cost-share.

          Authorization duration: 2 years


          N/A
          		127/1/20246/6/202510/1/2024 1:15 AMNo presence informationsrv_ppsgw_P
          Rx.01.33 Off-Label Use 
          N/A
          		N/AN/A
          459
            
          		10/1/2024Rx.01.266CommercialOyenusi, OluwadamilolaQ2-2024
          Hemolytic anemia is a disease that results in the premature death (hemolysis) of red blood cells (RBC) at a faster rate than the body can produce. Hemolytic anemia can be categorized as intrinsic and extrinsic. Intrinsic hemolytic anemia is genetically inherited and results in abnormalities in the cell membrane and overall blood cell production. Extrinsic hemolytic anemia is acquired as a secondary effect resulting from certain immunologic diseases, infections and medications. The glycolytic pathway is a metabolic pathway that breaks down glucose into pyruvate via the Pyruvate kinase (PK) enzyme, which leads to the production of ATP and NADH. A deficiency in the pyruvate kinase enzyme in homozygous patients causes a defect in the glycolytic pathway that is known to cause hemolytic anemia. The exact mechanism of hemolysis is unknown.

          Mitapivat is a Pyruvate Kinase activator that targets defective PK enzymes in RBC’s. 

          Mitapivat (Pyrukynd®) is indicated for the treatment hemolytic anemia in adults with a PK enzyme deficiency.



          ​The intent of this policy is to communicate the medical necessity criteria for Mitapivat (Pyrukynd®) as provided under the member's prescription drug benefit. 

          INITIAL CRITERIA: Mitapivat (Pyrukynd®) is approved when ALL of the following are met: 

           

          1. Diagnosis of hemolytic anemia confirmed by the presence of chronic hemolysis (e.g., increased indirect bilirubin, elevated lactated dehydrogenase [LDH], decreased haptoglobin, increased reticulocyte count); and
          2. Diagnosis of pyruvate kinase deficiency confirmed by molecular testing of ALL of the following mutations on the PLKR gene:
            1. Presence of at least 2 variant alleles in the pyruvate kinase liver and red blood cell (PKLR) gene, of which at least 1 was a missense variant; and
            2. Member is not homozygous for the c.1436G>A (p.R479H) variant; and 
            3. Member does not have 2 non-missense variants (without the presence of another missense variant) in the PKLR gene; and 
          3. Hemoglobin is less than or equal to 10g/dL; and 
          4. Member has symptomatic anemia or is transfusion dependent; and 
          5. Other causes of hemolytic anemias (e.g., infections, toxins, drugs) were ruled out; and 
          6. Member is 18 years of age and older; and 
          7. Prescribed by or in consultation with a hematologist 

           

          Initial authorization duration: 6 months 

           

          REAUTHORIZATION CRITERIA: Mitapivat (Pyrukynd®) re-approved when ALL of the following are met: 

          1. Documentation of positive clinical response to therapy (e.g., hemoglobin greater than or equal to 1.5g/dL from baseline sustained on 2 or more follow ups (weeks 16, 20 and 24) during the fixed dose period without transfusions; reduction in transfusions of greater than or equal to 33% in the number of red blood cell units transfused during the fixed dose period compared with the member's historical transfusion burden; improvement in markers of hemolysis from baseline (e.g., bilirubin, lactated dehydrogenase [LDH], haptoglobin, reticulocyte count)); and 
          2. Prescribed by or in consultation with a hematologist 

           

          Reauthorization duration: 12 months 


          None

          Pyrukynd® (mitapivat) [prescribing information]. Agios Pharmaceuticals, Inc.; February 2022. https://www.pyrukynd.com/hcp/. Accessed August 4, 2024

          Braunstein EM. Glycolytic Pathway Defects. Merck & Co., Inc., Rahway, NJ.; June 2022. https://www.merckmanuals.com/professional/hematology-and-oncology/anemias-caused-by-hemolysis/glycolytic-pathway-defects. Accessed August 4, 2024.




          		37/1/20246/6/202510/1/2024 1:16 AMNo presence informationsrv_ppsgw_P
          ​Rx.01.33 Off Label Use​
          ​Brand Name​Generic Name
          ​Pyrukynd​Mitapivat

          		N/AN/A
          460
            
          		10/1/2024Rx.04.2Claim Payment PolicyOyenusi, OluwadamilolaQ2-2024

          Presently, the FDA requires prescription drugs to demonstrate safety and efficacy prior to marketing, however, this was not always mandatory.  In 1906, the Pure Food and Drug Act prohibited adulterated, misbranded, poisonous or deleterious drugs from being manufactured, sold or transported.  The Pure Food and Drug Act was repealed and replaced with the Federal Food, Drug, and Cosmetic Act of 1938, which required evidence of safety for new drugs.  The law was amended further in 1962 to strengthen the requirements for safety and add an additional requirement for a manufacturer to demonstrate efficacy of the drug.

          The Orange Book identifies FDA approved drugs that have undergone the required safety and efficacy requirements of the Federal Food, Drug, and Cosmetic Act.  If a medication is not included in the orange book, it has not demonstrated safety and efficacy in accordance with the Federal Food, Drug, and Cosmetic Act requirements.  Drugs that entered the market based solely on safety and drugs that were on the market prior to 1938 are not included in the Orange Book. 

          Some drugs, mostly older products, are available on the market despite lacking FDA approval for a variety of historical reasons.  Examples include, but are not limited to, a manufacturer combining two approved products into a combination product without obtaining approval and a manufacturer marketing a currently approved product without obtaining FDA approval. 

           

          Prescription Drugs are defined by the plan as:

          A Legend Drug or Controlled Substance, which:

          • Has been approved by the Food and Drug Administration(FDA) for a specific use; and
          • Can, under federal or state law, be dispensed only pursuant to a Prescription Order

           

          A non-FDA approved drug will be considered for formulary inclusion if all the following criteria are met:

          • The drug entered the market prior to 1938; and
          • The drug is not commercially available in an FDA approved form of the same route of administration; and
          • The drug meets the criteria outlined in the Experimental/Investigational Use Policy

          The prescription drug benefit covers certain prescription drugs approved by the FDA pursuant to a prescription order.  Details of covered drugs may be found in the member’s benefit booklet.

           


          The intent of this policy is to communicate the prescription drug benefit coverage based on medical necessity of drugs that are not approved by the Food and Drug Administration (FDA).



          Coverage is subject to the terms, conditions, and limitations of the member's contract.

          Prescription drugs that are commercially available but not approved by the FDA are not considered a covered benefit.

          Some prescription drugs that are not FDA approved, and not otherwise excluded, will be covered under the pharmacy benefit for certain plans as required by the Patient Protection and Affordable Care Act (PPACA) or as defined in the member's benefit booklet. These items include but may not be limited to the following products as listed:

          • Prenatal vitamins, oral
          • Preventative vitamins and minerals as required by the PPACA
          • Cholecalciferol (vitamin D3) 50,000 units*
          • Sulfuric acid/phenolsulfonic acid solution*

           

          Some prescription drugs that came to market prior to 1938, prior to the current FDA approval process, and not otherwise excluded, will be covered under the prescription drug benefit if they are deemed medically accepted as defined in the Off-Label Use policy.  These items include but may not be limited to the following products as listed: 

          • Aluminum chloride topical 
          • Hydrocortisone suppositories
          • Hyoscyamine 
          • Phenobarbital 
          • Opium tincture 
          • Morphine suppositories 
          • Sodium chloride for inhalation 
          • Homatropine ophthalmic
          • Thyroid products (e.g., Armour Thyroid, Nature-Thyroid, NP Thyroid, WP Thyroid) 
          • Phenazopyridine HCL (Pyridium) 100mg and 200mg tablets 
          • Nitro-time CPCR 
          • Salsalate tablet 


          *Exceptions will be made for these products to meet essential health benefit requirements


          Academy of Managed Care Pharmacy. Practice Advisory on Unapproved Medications. Available from: https://www.amcp.org/sites/default/files/2019-03/Practice%20Advisory%20on%20Unapproved%20Meds%20_memohead_.pdf. Accessed August 4, 2024.

          US Food and Drug Administration. Federal Food and Drugs Act of 1906. Available from: https://www.fda.gov/about-fda/changes-science-law-and-regulatory-authorities/part-i-1906-food-and-drugs-act-and-its-enforcement. Accessed August 4, 2024.

          US Food and Drug Administration. Laws Enforced by FDA. Available from https://www.fda.gov/regulatoryinformation/lawsenforcedbyfda/default.htm . Accessed August 4, 2024.

          US Food and Drug Administration. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Available from: http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm. Accessed August 4, 2024.

          US Food and Drug Administration. Orange Book Preface. Available from: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/ucm079068.htm. Accessed August 4, 2024.

          US Food and Drug Administration. Unapproved Prescription Drugs: Drugs Marketed in the United States That Do Not Have Required FDA Approval. Available from: https://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/enforcementactivitiesbyfda/selectedenforcementactionsonunapproveddrugs/default.htm . Accessed August 4, 2024.

          Preventive Health Services. Available from: https://www.healthcare.gov/coverage/preventive-care-benefits/. Accessed August 4, 2024.

          Barowsky H, Schwartz SA. Method for Evaluating Diphenoxylate Hydrochloride: Comparison of Its Antidiarrheal Effect with that of Camphorated Tincture of Opium. JAMA. 1962;180(12):1058-1060.

          Beckwith MC. Diarrhea in Palliative Care Patients. Journal of Pharmaceutical Care in Pain & Symptom Control. 2010;7(4):91-108.​


          		137/1/20246/6/202510/1/2024 1:16 AMNo presence informationsrv_ppsgw_P

          Rx.04.5 Prescription Vitamins, Dietary Supplements, and Medical Foods 

          Rx.01.33 Off-Label Use   


          N/A
          		N/AN/A
          461
            
          		10/1/2024Rx.01.33CommercialOyenusi, OluwadamilolaQ2-2024

          The US Food and Drug Administration (FDA) approves labeling that details uses for which a pharmaceutical agent can be marketed.  The approved uses identify the specific disease states that the agent has been shown to be safe, efficacious and meet all clinical requirements set forth by the FDA. An off-label or unlabeled use of a prescription drug or biologic is a use that has not been approved by the US Food and Drug Administration (FDA) and which is not identified in package labeling. Use of a drug for any indication, dose or dose frequency, treatment duration, patient population, or route of administration other than those approved by the FDA and listed on the label or packaging insert is considered an off-label or unlabeled use.Off-label use of prescription drugs and biologics not meeting the medical necessity criteria is considered experimental/investigational and may not be a covered by the prescription drug benefit.
           
          In determining whether there is clinical evidence to support a medical necessity determination, the pharmacy benefits manager ​ will consider the quality of the published evidence as well as an assessment of the following information as submitted by the requesting physician. Off-label uses are medically accepted if they are supported in either of the following:

          (1) one or more authoritative compendia, and none list it as not indicated, unsupported, not recommended, or equivalent terms; or

          (2) in peer-reviewed medical literature.

          Reliable evidence must demonstrate that the proposed off-label use for the specified medical condition is safe and effective and that the treatment's beneficial effects outweigh its risks.

          Peer-reviewed medical literature includes scientific, medical, and pharmaceutical publications in which original manuscripts are published only after having been critically reviewed for scientific accuracy, validity, and reliability by unbiased, independent experts prior to publication. In order for a use to be supported by clinical research, it must have been studied in at least two clinical trials conducted at different centers, and the results must have been published in national or international peer-reviewed journals with an editorial committee composed of physicians. Peer-reviewed medical literature does not include in-house publications of pharmaceutical manufacturing companies or abstracts (including meeting abstracts).

          According to the National Cancer Institute, clinical trials are usually conducted in a series of steps called phases. These are outlined as follows:

          Phase 0 trials are the first step in testing a new agent in people. Phase 0 trials will evaluate how the new agent is processed in the body and how it exerts its clinical effects in the body. Phase 0 trials enroll a small number of individuals (10-15 individuals) who are administered a very small amount of the new agent.

          Phase I trials evaluate what dose is safe, how a new agent should be given (by mouth, injected into a vein, or injected into the muscle), and how often. Researchers watch closely for any harmful side effects. Phase I trials usually enroll a small number of individuals (20 or more individuals) and take place at only a few locations. The dose of the new therapy or technique is increased a little at a time. The highest dose with an acceptable level of side effects is determined to be appropriate for further testing.

          Phase II trials study the safety and effectiveness of an agent or intervention and evaluate how it affects the human body. Phase II studies usually focus on a particular aspect of a disease and include fewer than 100 patients.

          Phase III trials compare a new agent or intervention (or new use of a standard one) with the current standard therapy. Participants are randomly assigned to the standard group or the new group, usually by computer. This method, called randomization, helps to avoid bias and ensures that human choices or other factors do not affect the study's results. In most cases, studies move into Phase III testing only after they have shown promise in Phases I and II. Phase III trials often include large numbers of individuals across the country.

          Phase IV trials are conducted to further evaluate the long-term safety and effectiveness of a treatment. They usually take place after the treatment has been approved for standard use. Several hundred to several thousand people may take part in a Phase IV study. These studies are less common than Phase I, II, or III trials.


          Prescription pharmaceutical agents available in the United States have FDA approved labeling. The label specifies which disease states a drug can be used to treat. However, use of a pharmaceutical agent may expand past the approved labeling and into what is known as off-label use. Coverage for off-label or experimental use will require Prior Authorization.  

          Off-label uses are medically accepted and thus approved when ONE of the following is met:

          1. The narrative text in American Hospital Formulary Service--Drug Information (AHFS-DI®) is supportive of the use; or
          2. The use is classified as Category 1 or 2A by National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium™; or
          3. The use is classified as Class I or Class IIa in Micromedex®; or
          4. Adequate published clinical research (supplied by the provider) as defined below:

          Authorization duration: 2 years

          PUBLISHED CLINICAL RESEARCH

          In order for an off-label use to be supported by published clinical research, all of the following criteria must be met:

          A. The prescription drug or biologic must have been studied in at least two clinical trials conducted at different centers and the results must have been published in a national or international peer-reviewed journals with an editorial committee composed of physicians.  Peer-reviewed medical literature includes scientific, medical, and pharmaceutical publications.  It does not include in-house publications of pharmaceutical manufacturing companies or abstracts (including meeting abstracts).

          1. A use is considered supported by clinical research when it appears in at least two Phase III clinical trials that have definitively demonstrated its safety and effectiveness as an appropriate medical treatment for the condition.  If no Phase III trial evidence is available, at least two Phase II clinical trials with reasonably large patient samples showing consistent results of safety and efficacy may be considered in certain instances (e.g. rare diseases in which a Phase III study might be difficult to complete in a reasonable period of time after completion of the Phase II studies. Or when overwhelmingly good evidence of safety and effectiveness is noted in Phase II studies)

          B. Reliable evidence must demonstrate that the proposed off label use for the specified medical condition is safe and effective and that the beneficial effects of the treatment outweigh its risks.
          C. In determining whether there is supportive clinical evidence for a particular use of a prescription drug or biologic, the Company considers the quality of the evidence in published, peer-reviewed medical literature.  Among other things, such consideration involves the assessment of the following:

          1. The prevalence and life history of the disease when evaluating the adequacy of the number of subjects and the response rate
          2. The effect on the individual's well-being and other responses to therapy that indicate effectiveness (e.g. reduction in mortality, morbidity, and signs and symptoms)
          3. Whether the clinical characteristics of the beneficiary and the indication are adequately represented in the published evidence
          4. Whether the study is appropriate to address the clinical question, such as:
            1. If the study design is appropriate to address investigative questions (e.g. in some clinical studies, it may be unnecessary or not feasible to use randomized, double-blind trial, placebos, or crossover)
            2. If non-randomized clinical trials with a significant number of subjects may be a basis for supportive clinical evidence for determining accepted uses of drugs
            3. Generally, case reports are considered uncontrolled, are based on anecdotal information, and do not provide adequate supportive clinical evidence for determining accepted uses of drugs.
          5. The off-label use is supported by published clinical research and the results have been published in major, peer-reviewed medical journals such as, but not limited to:

           

          American Journal of MedicineGynecologic Oncology
          American Journal of PsychiatryInternational Journal of Radiation, Oncology, Biology and Physics
          Annals of Internal MedicineJournal of Clinical Oncology
          Annals of OncologyJournal of Obstetrics and Gynecology
          Annals of Surgical OncologyJournal of Pediatrics
          Archives of Pediatric and Adolescent MedicineJournal of the National Cancer Institute
          Biology of Blood and Marrow TransplantationJournal of the National Comprehensive Cancer Network (NCCN)
          British Journal of CancerJournal of Urology
          British Journal of HematologyLancet
          British Medical JournalLancet Oncology
          CancerLeukemia
          Clinical Cancer ResearchPediatrics
          DrugsRadiation Oncology
          European Journal of CancerThe Journal of the American Medical Association
          Bone Marrow TransplantationThe New England Journal of Medicine

           

          EXPERIMENTAL/INVESTIGATIONAL

          Prescription drugs that are considered experimental/investigational are not covered because the safety and/or efficacy of the drug for those purposes cannot be established by a review of the available published peer reviewed literature.  Prescription drugs and biologics are considered experimental/investigational for any of the following:

          1. The prescription drug or biologic has not received FDA approval for any use
          2. The off-label use of the prescription drug or biologic does not meet the medical necessity criteria listed in this policy or in any other specific Company Pharmacy Policy addressing a drug and/or biologic (i.e. the off-label use is not recognized by the appropriate compendia or published clinical research). This includes products granted orphan designation by the FDA.
          3. The FDA determined the prescription drug or biologic to be contraindicated for specific condition(s) or specific off-labels use(s)
          4. The off-label use is not medically accepted or not indicated by a compendium for specific conditions (i.e. the indication is Category 3 in NCCN, Class III in Micromedex®) or when the narrative text in AHFS-DI® is not supportive)
            1. The absence of narrative text for an off-label use is considered neither supportive nor non-supportive

           

          REQUIRED DOCUMENTATION

          The individual's medical record must reflect the medical necessity for the care provided.  These medical records may include but are not limited to records from the professional provider's office, hospital, nursing home, home health agency, therapies, and test reports.

          The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider.  All documentation is to be available to the Company upon request.  Failure to produce the requested information may result in a denial for the service.


          N/A
          N/A
          		167/1/20246/6/202510/1/2024 1:16 AMNo presence informationsrv_ppsgw_P
          N/A
          This policy applies to all drugs that have clinical management policies addressing them.
          		N/AN/A
          462
            
          		10/1/2024Rx.01.197CommercialOyenusi, OluwadamilolaQ2-2024

          Opioid analgesics are classified as full agonists, mixed agonist-antagonists, or partial agonists by their activity at opioid receptors. There are three major classes of opioid receptors in the central nervous system (CNS): mu, kappa, and delta. Mu-receptor activation causes analgesia, respiratory depression, miosis, reduced GI motility, and euphoria.  Kappa-receptor activation also causes analgesia, but may also produce effects such as dysphoria and hallucinations, which limit use.  Delta-receptor activation produces some analgesia but may also cause seizures at high doses and has some antidepressant effects.  Morphine-like opioid agonists have activity at the mu, kappa, and delta receptors, but have the highest affinity for the mu receptors1. Opioid agonists include natural opium alkaloids (e.g., codeine, morphine), semisynthetic analogs (e.g., hydrocodone, hydromorphone, oxycodone, oxymorphone), and synthetic compounds (e.g., fentanyl, levorphanol, methadone, sufentanil, tapentadol, tramadol). There is no defined maximum dose for most opioids. The ceiling to analgesic effectiveness is imposed only by adverse reactions. Adverse effects of opioids include constipation, nausea and vomiting, dizziness, sedation, respiratory depression2. Long-term use of high dose narcotics may also have significant adverse effects including but not limited to endocrinological effects, such as, hypogonadism, impotence in males, menstrual irregularities, and galactorrhea in women; and opioid induced hyperanalgesia caused by damage to the nociceptors thus increasing pain sensitivity3. 

          Opioid analgesics are commonly prescribed in pain management.  Pain is classified into non-cancer and cancer related pain. Non-cancer related pain may be acute or chronic while cancer-related pain may be a mixture of both2. When using opioid agents to manage pain, the choice should be made based on patient acceptance, pain intensity, analgesic effectiveness, pharmacodynamic, pharmacokinetic and side effect profiles. Like the treatment of many disease states, pain treatment should be initiated with the most effective agent with minimal side effects. Prior to starting patient on opioid pain management, pain severity and intensity should be thoroughly assessed using patient medical history, physical examination and different pain assessment tools4. In the management of mild non-cancer pain, the American Pain Society recommends the use of non-opioid analgesics such as acetaminophen and NSAIDs as first line agents. If pain relief is not adequate, opioid analgesics could be considered as the next line of treatment. Combination treatments of opioid with acetaminophen or NSAIDs are recommended when treating moderate to severe non-cancer pain. Common opioid analgesics like oxycodone and hydrocodone are often co-formulated with acetaminophen or NSAIDs and have a maximum dose to limit the amount of acetaminophen and NSAIDs exposure. It is recommended not to exceed 4000 mg of acetaminophen per day, 3200 mg of ibuprofen or 4000 mg (3900mg for controlled-, extended-, and delayed-release products) of aspirin daily.

          Pain that is associated with cancer or a malignant condition is known as cancer related pain. Cancer related pain may be acute and/or chronic. Pain related to cancer is usually the result of damage to parts of the body from cancer metastasis or therapies such as chemotherapy, radiation and surgical procedures. Opioid analgesics play an important role in pain management for oncology patients. The World Health Organization (WHO) developed a pain relief regimen known as the WHO's Pain Relief Ladder which provides guidelines for pain management in cancer patients5. Like non-cancer related pain, opioid analgesics are reserved for moderate to severe cancer pain. Patients with mild pain should try non-opioid analgesics such as acetaminophen, ibuprofen, or naproxen first. Opioid agents or opioid combination are reserved for moderate to severe cancer pain or when inadequate pain relief is not achieved with non-opioid analgesics.

          The potency of opioids is not consistent across all medications.  Morphine milligram equivalents (MME) is a conversion factor used to standardize the dose of an opioid into the equivalent dose of morphine to easily compare doses of different opioid agents and assess the risk of the doses.  Conversion factors are included in the table below. 

          Several utilization tools are in place to prevent abuse and overuse of opioids.  These include MME limits, days' supply limits, and quantity limits.

          1. MME limits: MME Limits are in place to limit the total dosage of opioids a patient can receive in a day. Regimens, whether single drug or multiple drugs, that exceed 90 MME are subject to MME limit.  Higher doses of opioids, along with other factors, are associated with increased risk of opioid overdose.  The threshold of 90 MME is based on the recommendations from the Centers for Disease Control and Prevention: “When opioids are started, clinicians should prescribe the lowest effective dosage. Clinicians should use caution when prescribing opioids at any dosage, should carefully reassess evidence of individual benefits and risks when considering increasing dosage to ≥50 morphine milligram equivalents (MME)/day, and should avoid increasing dosage to ≥90 MME/day or carefully justify a decision to titrate dosage to ≥90 MME/day."   
          2. Days' Supply Limits: Day supply limits are in place to limit the total days a patient can receive opioids. “The probability of long-term opioid use increases most sharply in the first days of therapy, particularly after 5 days or 1 month of opioids have been prescribed," according to the Centers for Disease Control and Prevention (CDC).  Long-term opioid use often begins with treatment of acute pain. To address these statistics, all opioids individual opioids with a dose less than or equal to 90 morphine milligram equivalents (MME) are subject to 5 days' supply limit.  Continuation beyond five days requires review.
          3. Quantity Limits: Quantity limits are in place to optimize doses and achieve the prescribed dose using the least number of tablets, capsules, patches, films, liquids, suppositories, etc. that a patient can receive in a day. Opioids are subject to limits on the quantity per day. While opioid doses are variable and may have no true maximum, quantity limits are in place to address safety concerns, including abuse, addiction, and diversion. The limits in this policy restrict quantities to either the daily MME of 90 mg of a single agent or the FDA limit of additional product components such as 4 grams of acetaminophen, 3.2 grams of ibuprofen or 4 grams of aspirin

          Morphine Milligram Equivalent (MME) Conversion Factors for Commonly Prescribed Opioid Analgesics

          Opioid Oral Morphine Milligram Equivalent (MME) Conversion Factors12​
          Type of Opioid (strength units)MME Conversion Factor
          Buprenorphine film/tablet (mg)30
          Buprenorphine patch (mcg/hr)12.6
          Buprenorphine film* (mcg)0.03 
          Butorphanol (mg)7 
          Codeine (mg)0.15 
          Dihydrocodeine (mg)0.25 
          Fentanyl buccal or SL tablets, or lozenge/troche (mcg)0.13 
          Fentanyl film or oral spray (mcg)0.18 
          Fentanyl nasal spray (mcg)0.16 
          Fentanyl patch** (mcg)7.2
          Hydrocodone (mg)1 
          Hydromorphone (mg)5
          Levorphanol tartrate (mg)11 
          Meperidine hydrochloride (mg)0.1 
          Methadone (mg)4.7
          Morphine (mg)1 
          Opium (mg)1 
          Oxycodone (mg)1.5 
          Oxymorphone (mg)3 
          Pentazocine (mg)0.37 
          Tapentadol (mg)0.4 
          Tramadol (mg)0.2 


          These conversion factors will be used to determine the MME/day of all opioids being prescribed.  Calculate the total daily dose of the opioid in the left column and multiply by the conversion factor to determine to MME/ day.  If multiple agents are being used, add the MME of the individual agents to get the total MME of the regimen.    These values do not constitute clinical guidance or recommendations for converting patients from one form of opioid analgesic to another.  Extra caution applies to methadone (conversion factor depends on dose) and fentanyl (patches are dosed in mcg/hour rather than mg/day).  Please consult the manufacturer's full prescribing information for such guidance. 

          12 These conversion factors are based on CMS “Opioid Oral Morphine Milligram Equivalent (MME) Conversion Factors" found here: https://www.cms.gov/Medicare/Prescription-Drug-Coverage/PrescriptionDrugCovContra/Downloads/Opioid-Morphine-EQ-Conversion-Factors-Aug-2017.pdf

          *The MME conversion factor for buprenorphine patches is based on the assumption that one milligram of parenteral buprenorphine is equivalent to 75 milligrams of oral morphine and that one patch delivers the dispensed micrograms per hour over a 24 hour day. Example: 5 ug/hr buprenorphine patch X 24 hrs = 120 ug/day buprenorphine = 0.12 mg/day = 9 mg/day oral MME. In other words, the conversion factor not accounting for days of use would be 9/5 or 1.8. However, since the buprenorphine patch remains in place for 7 days, we have multiplied the conversion factor by 7 (1.8 X 7 = 12.6). In this example, MME/day for four 5 µg/hr buprenorphine patches dispensed for use over 28 days would work out as follows: Example: 5 ug/hr buprenorphine patch X (4 patches/28 days) X 12.6 = 9 MME/day. Please note that because this allowance has been made based on the typical dosage of one buprenorphine patch per 7 days, you should first change all Days Supply in your prescription data to follow this standard, i.e., Days Supply for buprenorphine patches= # of patches x 7

          **The MME conversion factor for fentanyl patches is based on the assumption that one milligram of parenteral fentanyl is equivalent to 100 milligrams of oral morphine and that one patch delivers the dispensed micrograms per hour over a 24 hour day. Example: 25 ug/hr fentanyl patch X 24 hrs = 600 ug/day fentanyl = 60 mg/day oral morphine milligram equivalent. In other words, the conversion factor not accounting for days of use would be 60/25 or 2.4. However, since the fentanyl patch remains in place for 3 days, we have multiplied the conversion factor by 3 (2.4 X 3 = 7.2). In this example, MME/day for ten 25 µg/hr fentanyl patches dispensed for use over 30 days would work out as follows: Example: 25 ug/hr fentanyl patch X (10 patches/30 days) X 7.2 = 60 MME/day. Please note that because this allowance has been made based on the typical dosage of one fentanyl patch per 3 days, you should first change all Days Supply in your prescription data to follow this standard, i.e., Days Supply for fentanyl patches= # of patches X 3.

          Butalbital containing products in tension-type headache

          Butalbital is a barbiturate that is commonly prescribed in combination with acetaminophen and caffeine to treat different types of headaches such as tension-type and migraines. It works by decreasing motor activity and depress the sensory cortex causing CNS depression ranging from sedation to general anesthesia6. The analgesia effect of barbiturate is unknown. However, there are limited studies that show the efficacy of butalbital in the treatment of tension type headache and migraine7. In addition, overuse of barbiturate products could lead to dependency, withdrawal, and drug-induced headache. Therefore, when selecting a treatment for tension-type headache as well as other types of headaches, butalbital containing products should only be used if first line analgesics like acetaminophen or NSAIDs provide insufficient relief. In acute management, butalbital products should not be used more than 3 days7. 

          Opioid Containing Cough and cold products

          Opioid containing cough and cold products are thought to suppress cough via action on the central cough center. While the products are widely used, data are limited regarding efficacy.  Like opioids used to treat pain, cough and cold products containing an opioid are subject to days' supply limits, quantity limits, and morphine milligram equivalent (MME) limits.

           

          Days' Supply and Quantity limits

          Quantity limits are designed to allow a sufficient supply of medication based upon FDA-approved or medically accepted maximum daily doses and length of therapy of a particular drug. Quantity limits may be expressed as quantity over time or maximum daily dose.  Additionally, there are some medications to which a limit on the days' supply is applied.

          1. Quantity over time: This quantity limit is based on dosing guidelines over a rolling time period, usually 30 days.
          2. Maximum daily dose (maximum quantity per day): This quantity limit is based on maximum number of units of the drug allowed per day.
          3. Days' supply limit: This limits the numbers of days of therapy within a defined period of time. Maximum daily dose applies to days' supply limits.

          Summary Of Utilization Managment

          Summary Table of Criteria on Opioid Medications​​​
          CriteriaShort Acting OpioidsLong Acting Opioids (including opioid patches)Transmucosal Immediate Release Fentanyl (TIRF)
          MME LimitYesYesYes
          Day Supply LimitYes*NoNo
          Quantity LimitYesYesYes
          Opioid Prior AuthorizationNo*YesYes

          *Note: short-acting opioids are available without prior authorization for two 5-day supplies within 60 days or less. Greater than a total of a 10 day supply within 60 days requires prior authroization.


          ​The intent of this policy is to communicate the medical necessity criteria including prior authorization, quantity limits, and days’ supply for opioid analgesics, buprenorphine containing medication assistant treatments, and butalbital containing headache medications as provided under the member's prescription drug benefit.



          PRIOR AUTHORIZATION

          I. Transmucosal Immediate Release Fentanyl (TIRF) Product fentanyl citrate is considered medically necessary when:
          A. INITIAL CRITERIA [Authorization duration: 1 year]: Transmucosal Immediate Release Fentanyl (TIRF) Products are considered medically necessary when there is documentation of ALL of the following:

          1. Use for breakthrough pain associated with active cancer treatment or cancer not in remission in members who are receiving long-acting opioid therapy; and

          2. Member is 18 years of age or older (16 years of age and older for fentanyl citrate); and

          3. Member is tolerant to current opioid therapy (i.e., adherence to one of the following regimens for one week or longer: 25mcg of transdermal fentanyl hourly, 30mg of oxycodone daily, 60mg of oral morphine daily, 8mg of oral hydromorphone daily, 25mg of oral oxymorphone daily; or an equianalgesic dose of another opioid)

          B. REAUTHORIZATION CRITERIA [Authorization duration: 1 year]:  Transmucosal Immediate Release Fentanyl (TIRF) product is re-approved when there is documentation of continued use for breakthrough pain associated with active cancer treatment or cancer not in remission in members who are currently receiving long-acting opioid therapy
          II. Opioid regimens containing greater than 90 morphine milligram equivalents per day, long acting opioids, and short acting opioids for continuation beyond 30 days [Authorization duration: 1 year] - are considered medically necessary as follows:

          A. INITIAL CRITERIA: The requested product or regimen is considered medically necessary when there is ONE of the following:  
          1. Pain associated with active cancer treatment, cancer not in remission, or sickle cell anemia (regardless of age); OR
          2. Severe, persistent chronic pain with documentation of diagnosis associated with pain and ALL of the following:

              1. Documentation of a current patient-prescriber opioid treatment agreement (signed within one year of request); and
              2. ONE of the following
                1. Regimen prescribed by or in consultation with a pain management specialist within last 6 months. Must provide name of physician and date of last visit. Physician must be Board Certified by one of the following:
                  1. American Board of Anesthesiology- Pain Management; or
                  2. American Board of Psychiatry & Neurology- Pain Management; or
                  3. American Board of Physical Medicine & Rehabilitation; or
                  4. American Osteopathic Association- Pain Management

                    or
                2. The member has been evaluated for at least TWO of the following therapies:
                  1. Physical therapy; or
                  2. Psychotherapy; or
                  3. Adjuvant medications specific to causative condition including but not limited to any of the following: antidepressants, anticonvulsants, muscle relaxants, anti-inflammatory agents.

          B. REAUTHORIZATION CRITERIA [Authorization duration: 1 year]:  Re-authorization of the requested opioid product or regimen containing greater than 90 morphine milligram equivalents per day, long acting opioids, and short acting opioids for continuation beyond 30 days is considered medically necessary when there is documentation of ONE of the following:

          1. Pain associated with active cancer treatment, cancer not in remission, or sickle cell anemia (regardless of age) AND documentation that a urine drug screen (UDS) will performed by prescriber within 1 year of request.

          OR

                2. Severe, persistent chronic pain with documentation of diagnosis associated with pain and ALL of the following:

            1. Documentation of a current patient-prescriber opioid treatment agreement (signed within one year of request); and
            2. documentation that a urine drug screen (UDS) will be performed by prescriber within 1 year of request.

          III. Appropriate Utilization with Medication Assistant Treatments (MAT) for opioid use disorder - [Authorization duration: 2 months] - Opioid analgesics will require prior authorization for medical necessity when filled within two months of a paid claim for either buprenorphine/naloxone (Bunavail®/Suboxone®/Zubsolv®) or buprenorphine sublingual tablet. Opioid analgesic products are approved in patients that have received buprenorphine/naloxone or buprenorphine in the previous two months when there is documentation of a treatment plan showing discontinuation of buprenorphine containing MAT.
           
          DAYS' SUPPLY AND QUANTITY LIMITS
           
          I. Day supply limit Criteria
          A. Short-acting opioids for short term use (greater than two 5-day fills within 60 days for 18 and older, and greater than two 3-day fills within 60 days for age less than 18)  [Authorization duration: 1 month for a 30 days' supply] - an exception is approved when ALL of the following are met:
          INITIAL CRITERIA

          1. Diagnosis of acute pain; and
          2. Prescriber reviewed member's history in state Prescription Drug Monitoring Program website; and
          3. Prescriber counseled member (or member's representative) on risk of addiction; and
          4. Substance abuse screening done by prescriber

          REAUTHORIZATION CRITERIA see Opioid regimens containing greater than 90 morphine milligram equivalents per day, long acting opioids, and short acting low dose opioids for continuation beyond additional 30 days Prior Authorization criteria under section under section II.A above 

          B. Opioid containing cough and cold products are limited to two five (5) day fills within 60 days for 18 and older and two 3-day fills within 60 days for age less than 18 - an exception is approved when
          INITIAL CRITERIA: there is documentation of inadequate response or inability to tolerate non-opioid therapies for the indication [Authorization duration 1 month]
          EAUTHORIZATION CRITERIA: Documentation the underlying etiology of cough has been identified and treated, if applicable (e.g,, allergic rhinitis, asthma, GERD) [Authorization duration 6 months]

          C. Butalbital containing headache products are limited to one five (5) day fill within 30 days.  Opioid containing headache products are limited to one three (3) day fill within 30 days for less than 18 years of age, an exception is approved as follows: 

          INITIAL CRITERIA [Authorization duration: 3 months]: All of the following:

            1. Diagnosis of one of the following:
              1. Tension-type or muscular headache
              2. Migraine headache
            2. Member is 12 years of age or older
            3. Inadequate response or inability to tolerate TWO of the following:
              1. At least two triptans
              2. Non-steroid anti-inflammatory drugs (e.g., ibuprofen, naproxen)
              3. Neuroleptics (e.g., prochlorperazine, metoclopramide)
              4. Dihydroergotamine

           REAUTHORIZATION CRITERIA: [Authorization duration: 1 year]: All of the following:

            1. Diagnosis of one of the following:
              1. Tension-type or muscular headache
              2. Migraine headache
            2. Member is 12 years of age or older
            3. Prescribed by or in consultation with a neurologist or a headache specialist, or pain specialist
            4. Inadequate response or inability to tolerate NSAIDs
            5. Ongoing assessment of medication-overuse headache

          II. Quantity limit Criteria –
          A. Opioid pain products [authorization duration = 1 year] An increased quantity of an opioid medication is approved when there is documentation of ALL of the following:

          1. Current patient-prescriber opioid treatment agreement (signed within one year of request); and
          2. The requested dose and frequency do not exceed FDA approved dosing or are supported by compendia; and
          3. ONE of the following:
            1. The dose cannot be achieved with commercially available clinical dosage forms; or
            2. Documentation indicating medical necessity for a quantity that exceeds the plan limit (e.g. GI malabsorption).

          B. Cough and cold products [Authorization duration: 1 month for initial; 6 months for reauthorizations] - An increased quantity of an opioid containing cough and cold medication is approved when there is documentation of ALL of the following:

          1. The requested dose and frequency do not exceed FDA approved dosing or are supported by compendia; and
          2. Documentation of diagnosis requiring long-term therapy with requested cough/ cold medications; and
          3. Inadequate response or inability to tolerate non-opioid therapies for the indication

          C. Butalbital containing headache products [Authorization duration:1 year] - An increased quantity of a butalbital containing headache medication is approved when there is documentation of ALL of the following:

          1. The requested dose and frequency do not exceed FDA approved dosing or are supported by compendia; and
          2. Inadequate response or inability to tolerate prophylactic therapy; and
          3. Prescribed by or in consultation with a neurologist, headache specialist or pain specialist.

          D. Buprenorphine/ naloxone (Bunavail®/Suboxone®/Zubsolv®) and buprenorphine sublingual tablet [Authorization duration: 6 months]: buprenorphine/ naloxone or buprenorphine for the treatment of opioid use disorder are approved in quantities greater than those specified in the policy when ALL of the following are met:

            1. The requested dose and frequency do not exceed FDA approved dosing or are supported by compendia; and
            2. The dose cannot be achieved with commercially available dosage forms; and
            3. Inadequate response to lower doses 

          All products containing the active ingredients in the chart below are subject to the following:

          • Opioid regimens containing greater than 90 morphine milligram equivalents per day
          • Appropriate Utilization with Medication Assistant Treatments (MAT) for opioid use disorder
          Active ingredient
          Benzhydrocodone
          Codeine

          Dihydrocodeine
          Fentanyl
          Hydrocodone
          Hydromorphone
          Levorphanol                                    
          Meperidine                                                
          Methadone                                                      
          Morphine
          Opium
          Oxycodone                                                     
          Oxymorphone                         
          Tapentadol
          Tramadol                                               

           
          The table below identifies medications that are found in the following sections of this policy:

          • Transmucosal Immediate Release Fentanyl (TIRF) Products (¥ identifies impacted medications)
          • Opioid regimens containing greater than 90 morphine milligram equivalents per day, long acting opioids, and short acting low dose opioids for continuation beyond 30days (*identifies impacted long acting opioids)
          • Days' Supply and Quantity Limits
          Drug NameDays' Supply Limit Maximum Quantity per DayQuantity limit per rolling 30 days, unless otherwise specified (tablet, capsule)
          Acetaminophen/codeine #2 300/15mg tabtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812 
          Acetaminophen/codeine #3 300/30mg tabtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812 
          Acetaminophen/codeine #4 300/60mg tabtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
          Acetaminophen/codeine liquidtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1890mL 
          Benzhydrocodone/acetaminophen (Apadaz®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812 
          Buprenorphine film* (Belbuca®)No2​
          Buprenorphine patch* (Butrans®)No​4 patches
          Buprenorphine sublingual tablet 2mgNo4 
          Buprenorphine sublingual tablet 8mgNo3​
          Buprenorphine/naloxone (Suboxone® 2/0.5mg, 4/1mg)No4​
          Buprenorphine/ naloxone (Suboxone® 8/2mg)No3​
          Buprenorphine/ naloxone (Suboxone® 12/3mg)No2​
          Buprenorphine/naloxone (Zubsolv® 1.4/0.36mg, 2.9-0.71mg)No4​
          Buprenorphine/naloxone (Zubsolv® 5.7/1.4mg, 0.7/0.18mg)No3​
          Buprenorphine/naloxone (Zubsolv® 8.6/2.1mg)No2​
          Buprenorphine/naloxone (Zubsolv® 11.4-2.9mg)No1​
          Buprenorphine/naloxone 2.1/0.3mgNo4​
          Buprenorphine/naloxone 4.2/0.7mgNo3​
          Buprenorphine/naloxone 6.3/1mgNo1​
          Butalbital/apap (Allzital®)one 5-day fill per 30 days6 
          Butalbital/apap/caffeine without codeine (Esgic®, Fioricet®)one 5-day fill per 30 days6 
          Butalbital/apap/caffeine with codeine (Esgic®, Fioricet®/codeine)one 5-day fill per 30 days for 18 and over; one 3-day fill per 30 days for less than 186 
          Butalbital/asa/caffeine without codeine  one 5-day fill per 30 days6 
          Butalbital/asa/caffeine with codeineone 5-day fill per 30 days for 18 and over; one 3-day fill per 30 days for less than 186 
          Carisoprodol/ aspirin/ codeinetwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 188 
          Codeine sulfate tablets 15mg, 30mgtwo 5-day fills per 60 for 18 and older; two 3-day fills per 60 days for less than 1812 
          Codeine sulfate tablets 60mgtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
          Codeine/chlorpheniramine (Tuxarin® ER)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 182 
          Codeine/chlorpheniramine tabletstwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1820mL 
          Codeine/ chlorpheniramine solutiontwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860mL 
          Dihydrocodeine/ acetaminophen/ caffeine (Trezix®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1810 
          Fentanyl IR¥ (Actiq®, Fentora®)No4​
          Fentanyl nasal solution¥No1​
          Fentanyl patch*No​15 patches
          Guaifenesin/ codeine (Coditussin® AC)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860mL 
          Guaifenesin/ codeine (MAR-COF® CG)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1845mL 
          Guaifenesin/ codeinetwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1890mL 
          Hydrocodone bitartrate ER* (Hysingla® ER)No1 
          Hydrocodone bitartrate ER*No2​
          Hydrocodone/acetaminophen 2.5/325mg, 5/300mg,7.5/300mg, 5/325mg, 7.5/325mg tab (Xodol®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812​
          Hydrocodone/apap 10/325mg, 10/300mg tab (Xodol®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
          Hydrocodone/apap liquid (10mg/325mg/15ml, 2.5mg/167mg/5ml, 5mg/333mg/10ml, 7.5mg/325mg/15ml, 10mg/300mg/15ml)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1890mL 
          Hydrocodone/chlorpheniraminetwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1810mL 
          Hydrocodone/chlorpheniraminetwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 182 
          Hydrocodone/ homatropine (Hydromet®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1830mL 
          Hydrocodone/ homatropinetwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
          Hydrocodone/ibuprofen  two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 185 
          Hydromorphone (Dilaudid®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
          Hydromorphone 1mg/1ml liquid (Dilaudid®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812mL 
          Hydromorphone extended release* (Exalgo®)No2 
          Levorphanol tartrate 2mgtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
          Levorphanol tartrate 3mgtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 184 
          Meperidine 50mg/5ml liquidtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1867mL 
          Meperidine HCL (Demerol®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
          Methadone* tabs 5mg, 10mgNo6 
          Methadone solution* 5mg/5mlNo60mL 
          Methadone solution* 10mg/5mlNo30mL 
          Methadone solution* (Methadose concentrate,
          Methadose sugar-free concentrate) 10mg/1ml          		No6mL 
          Morphine 10mg/5ml liquidtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1845 mL 
          Morphine 20mg/5ml liquidtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1823 mL 
          Morphine concentrate 20mg/1ml, 10mg/0.5ml, 5mg/0.25ml liquidtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186mL 
          Morphine sulfate IR (MSIR®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186​
          Morphine sulfate ER capsules*No1​
          Morphine sulfate ER capsules* No2 
          Morphine sulfate SR* No3​
          Morphine sulfate SR* (MS Contin®)No3​
          Morphine sulfate/naltrexone*No2​
          Morphine suppositories 5mgtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1818 
          Morphine suppositories 10mgtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
          Morphine suppositories 20mg, 30mg two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
          Opium tincturetwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 18N/A 
          Oxycodone 7.5mg tab (Oxaydo®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 188 
          Oxycodone HCL (Oxy® IR/Roxicodone®/Oxaydo®, Roxybond®) 5mg caps/tabstwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812 
          Oxycodone HCL (Oxy® IR/Roxicodone®, Roxybond®), 10mg, 15 mg, 30mg caps/tabstwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
          Oxycodone 5mg/5ml liquidtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860 mL 
          Oxycodone highly concentrated liquid 20mg/1ml liquid two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186mL 
          Oxycodone HCL ER* (Oxycontin®)No3​
          Oxycodone ER* (Xtampza® ER)No2 
          Oxycodone/Acetaminophen, Endocet® (Percocet®, Nalocet®, Prolate®) 2.5/325mg tab, 2.5/300mg tab, 5/300mg, 5/325mg tabtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812 
          Oxycodone/Acetaminophen (Prolate®) 7.5/300mg tab, 10/300mg tabtwo 5-day fills
          per 60 days for
          18 and older;
          two 3-day fills
          per 60 days for
          less than 18          		6 
          Oxycodone/acetaminophen 7.5/325mg tab (Endocet®/Percocet®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 188 
          Oxycodone/acetaminophen 10/325mg tab (Endocet®/Percocet®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
          Oxycodone/acetaminophen 5mg/325mg/5ml liquidtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860 
          Oxycodone/aspirin 4.8355/325mg tabtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812 
          Oxycodone/Acetaminophen (Prolate®) 10-300mg/5ml solnTwo 5-days fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1830 ml 
          Oxymorphone HCLtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
          Oxymorphone HCL ER* No3 
          Phenylephrine/ brompheniramine/ codeinetwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1890mL 
          Phenylephrine/ chlorpheniramine/ codeine (Capcof®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860mL 
          Phenylephrine/ dexchlorpheniramine/ codeine (Pro-red® AC)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860mL 
          Promethazine/codeine 6.25-10mg/5mL syruptwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1830mL 
          Pseudoephedrine/ brompheniramine/ codeine (MAR-COF® BP)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860mL 
          Pseudoephedrine/codeine/ guaifenesin solution 30-10-100 MG/5MLtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1840mL 
          Pseudoephedrine/ dexbrompheniramine/ codeinetwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860mL 
          Tapentadol (Nucynta®) 50mgtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 184 
          Tapentadol (Nucynta®) 75mg, 100mgtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
          Tapentadol ER* (Nucynta® ER)No2 
          Tramadol 50mg, 25mg 8 
          Tramadol (Conzip®) 1 
          Tramadol/acetaminophen 8​
          Tramadol/celecoxib (Seglentis®)No4 
          Tramadol 100 mg 4 
          Tramadol (Qdolo®) 80ml 

          ​1. Respiratory depression: 21, 22, 30, 31, 32, 33, 34, 35, 40, 43  TIRFs (Actiq®, Fentora®, Subsys®), Lazanda®, Duragesic®, Hydromorphone (Dilaudid, Exalgo®), Methadone, Morphine Sulfate: ArymoTM ER, Avinza®, Kadian®, and MS Contin®, Morphabond ER®, Nucynta ER®/ Opana ER®, Oxycodone (Oxycontin®, oxycodone concentrate, OxaydoTM, Roxybond®), Zohydro ER™ (hydrocodone ER), Buprenorphine (Belbuca and Butrans), benzhydrocodone/acetaminophen (Apadaz®), codeine polistirex and chlorpheniramine (Tuzistra XR), codeine phosphate and chlorpheniramine maleate (Tuxarin®), levorphanol, Qdolo® (tramadol), Seglentis® (tramadol/celecoxib)


          Fatal respiratory depression has occurred in patients treated with the above listed opioid products, including following use in opioid-intolerant patients and improper dosing. Be sure to monitor for sign and symptoms of respiratory depression, especially during initiation of the drugs. The substitution of fentanyl sublingual/buccal for any other fentanyl product may result in fatal overdose. Because of the risk of respiratory depression, fentanyl products are contraindicated for use as an as-needed analgesic, or in the management of acute or postoperative pain, including headache/migraine and in opioid-intolerant patients. In addition, the concomitant use of fentanyl sublingual with CYP3A4 inhibitors may result in an increase in fentanyl plasma concentrations and may cause potentially fatal respiratory depression.

          For hydromorphone and ER products like morphine ER, oxycodone ER, hydrocodone ER, tapentadol ER, and oxymorphone ER products, instruct patients to swallow a whole tablet. Crushing, chewing, snorting, or dissolving tablets can cause rapid release and absorption that could lead to fatal overdose and even death. Note: Avinza® capsule contents may be sprinkled on applesauce and swallowed without chewing19. Hydromorphone is a potent Schedule II controlled opioid agonist. Schedule II opioid agonists have the highest potential for abuse and risk of producing respiratory depression. Alcohol, other opioids, and CNS depressants (sedative-hypnotics) potentiate the respiratory depressant effects of hydromorphone, increasing the risk of respiratory depression that might result in death.
           
          2. Medication errors: 32, 33 TIRFs (Actiq®, Fentora®, Subsys®), Lazanda®, codeine phosphate and chlorpheniramine maleate (Tuxarin®), codeine polistirex and chlorpheniramine (Tuzistra XR), Qdolo® (tramadol)

          Substantial differences exist in the pharmacokinetic profile of fentanyl sublingual/buccal compared with other fentanyl products that result in clinically important differences in the extent of absorption of fentanyl that could result in fatal overdose. When prescribing, do not convert patients on a mcg-per-mcg basis from any other fentanyl products to fentanyl sublingual/buccal. When dispensing, do not substitute a fentanyl sublingual/buccal prescription for other fentanyl products.

          3. Addiction and Abuse potential: 21, 22, 30, 31, 32, 33, 34, 42, 43 TIRFs (Actiq®, Fentora®, Subsys®), Lazanda®, Duragesic®, Hydromorphone (Dilaudid, Exalgo®), Methadone, Morphine Sulfate: ArymoTM ER, Avinza®, Kadian®, and MS Contin®, Morphabond ER®​, Nucynta ER®/ Opana ER®, Oxycodone (Oxycontin®, oxycodone concentrate, OxaydoTM, Roxybond®), Zohydro ER™ (hydrocodone ER), Buprenorphine (Belbuca and Butrans), benzhydrocodone/acetaminophen (Apadaz®), codeine phosphate and chlorpheniramine maleate (Tuxarin®), codeine polistirex and chlorpheniramine (Tuzistra XR), levorphanol, Qdolo® (tramadol), Seglentis® (tramadol/celecoxib)​

           All opioid analgesics regardless of formulation are classified as Schedule II controlled substance, with high abuse liability. They expose patients and drug users to the risk of opioid addiction, abuse, and misuse, which can lead to overdose and death. Diversion, addiction, and abuse potential should be considered when prescribing or dispensing opioid analgesics. Providers must monitor all patients regularly for the development of these behaviors or conditions. Due to the risk for misuse, abuse, addiction, and overdose, some products such as fentanyl sublingual/buccal is available only through a restricted program required by the Food and Drug Administration, called a Risk Evaluation and Mitigation Strategy (REMS). Under the Transmucosal Immediate Release Fentanyl (TIRF) REMS Access Program, outpatients, health care providers who prescribe to outpatients, pharmacies, and distributors must enroll in the program. Further information is available at http://www.TIRFREMSaccess.com or by calling 1-866-822-1483. 
           
          4. Cytochrome P450 3A4 interaction: 30, 31  TIRFs (Actiq®, Fentora®, Subsys®), Lazanda®, Duragesic®, Oxycodone (Oxycontin®, oxycodone concentrate, OxaydoTM ,Roxybond®), Zohydro ER™ (hydrocodone ER), benzhydrocodone/acetaminophen (Apadaz®), codeine polistirex and chlorpheniramine (Tuzistra XR), codeine phosphate and chlorpheniramine maleate (Tuxarin®), Qdolo® (tramadol), Seglentis® (tramadol/celecoxib)

          The concomitant use of fentanyl, oxycodone ER and hydrocodone ER with all cytochrome P450 3A4 (CYP3A4) inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving oxycodone ER and any CYP3A4 inhibitor or inducer.
           
          5. Accidental exposure 21, 22, 30, 31, 32, 33, 34, 42, 43: Duragesic®, Hydromorphone (Dilaudid, Exalgo®), Methadone, Morphine Sulfate: ArymoTM ER, Avinza®, Kadian®, and MS Contin®, Morphabond ER® , Nucynta ER®/ Opana ER®, Oxycodone (Oxycontin®, oxycodone concentrate, OxaydoTM Roxybond®), Zohydro ER™, Buprenorphine (Belbuca and Butrans), benzhydrocodone/acetaminophen (Apadaz®), codeine polistirex and chlorphniramine (Tuzistra XR), codeine phosphate and chlorpheniramine maleate (Tuxarin®), levorphanol, Qdolo® (tramadol), Seglentis® (tramadol/celecoxib)

          Deaths due to a fatal overdose of the above listed opioid analgesics have occurred when children and adults were accidentally exposed to the drugs. Strict adherence to the recommended handling and disposal instructions is of the utmost importance to prevent accidental exposure. Accidental ingestion of even 1 dose, especially in children, can result in a fatal overdose and death.

          6. Neonatal opioid withdrawal syndrome: 21, 22, 30, 31, 32, 33, 34, 44, 43 
          Prolonged use of opioid analgesics especially Duragesic®,  Hydromorphone (Dilaudid, Exalgo®), Methadone, Morphine Sulfate: ArymoTM ER, Avinza®, Kadian®, and MS Contin®, Morphabond ER® , Nucynta ER®/ Opana ER® (tapentadol ER, and oxymorphone ER), Zohydro ER™, Oxycodone (Oxycontin®, oxycodone concentrate, OxaydoTM, Roxybond®), Buprenorphine (Belbuca and Butran), benzhydrocodone/acetaminophen (Apadaz®), codeine phosphate and chlorpheniramine maleate (Tuxarin®), codeine polistirex and chlorpheniramine (Tuzistra XR), Qdolo® (tramadol), levorphanol , Seglentis® (tramadol/celecoxib)can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
           
          7. Exposure to heat: Duragesic® (31)
          Exposure of the fentanyl application site and surrounding area to direct external heat sources, such as heating pads or electric blankets, heat or tanning lamps, sunbathing, hot baths, saunas, hot tubs, and heated water beds may increase fentanyl absorption and has resulted in fatal overdose of fentanyl and death. Patients wearing fentanyl systems who develop fever or increased core body temperature due to strenuous exertion are also at risk for increased fentanyl exposure and may require an adjustment in the dose of fentanyl to avoid overdose and death.

          8. Life-threatening QT prolongation: Methadone 29

          QT interval prolongation and serious arrhythmia like torsades de pointes have occurred during treatment with methadone. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Closely monitor patients for changes in cardiac rhythm during initiation and titration of methadone.
           
          9. Treatment of opioid addiction: Methadone29

          For detoxification and maintenance of opioid dependence, methadone should be administered in accordance with the treatment standards cited in 42 CFR Section 8, including limitations on unsupervised administration.
           
          10. Interaction with alcohol 21, 22, 30, 31, 32, 33, 34, 35, 40: Morphine Sulfate: Avinza®, Kadian®, and MS Contin®, Nucynta ER®/ Opana ER®, Zohydro ER™, Oxycodone (Oxycontin®, oxycodone concentrate, OxaydoTM, Roxybond®), Buprenorphine (Belbuca and Butran), benzhydrocodone/acetaminophen (Apadaz®)

           When using with alcohol, all opioid analgesic products have the potential to cause excessive sedation and may increase blood concentration of certain opioids like tapentadol, oxymorphone, and morphine. This could lead to fatal overdose and death. Instruct patients to avoid alcoholic beverages or use prescription or nonprescription products that contain alcohol while taking opioid analgesics. 

          11. Information about oral morphine and oxycodone solution23, 29  : Morphine Sulfate: Avinza®, Kadian®, and MS Contin®, Oxycodone (Oxycontin®, oxycodone concentrate, OxaydoTM, Roxybond®)

           Morphine oral solution is available in 10 mg per 5 mL, 20 mg per 5 mL, and 100 mg per 5 mL (20 mg/mL) concentrations. The 100 mg per 5 mL (20 mg/mL) concentration is indicated for use in opioid-tolerant patients only. Take care when prescribing and administering morphine oral solution to avoid dosing errors due to confusion between different concentrations and between milligrams and milliliters, which could result in accidental overdose and death. Take care to ensure the proper dose is communicated and dispensed. Keep morphine oral solution out of the reach of children. In case of accidental ingestion, seek emergency medical help immediately.

          Oxycodone concentrated oral solution is available as a 20 mg/mL concentration and is indicated for use in opioid-tolerant patients only. Take care when prescribing and administering oxycodone concentrated oral solution to avoid dosing errors due to confusion between milligram and milliliter, and other oxycodone solutions with different concentrations, which could result in accidental overdose and death. Take care to ensure the proper dose is communicated and dispensed. Keep oxycodone out of the reach of children. In case of accidental ingestion, seek emergency medical help immediately.
           
          12. Abuse Deterrent Technology: Oxaydo™ (37)

           This formulation incorporates Acura's patented AVERSION® (abuse-deterrent) Technology which Acura states is a patented mixture of gelling ingredients and nasal irritants designed to address common forms of opioid abuse. OXAYDO can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing in situations where there is concern about an increased risk of misuse or abuse. OXAYDO may be abused by crushing, chewing, snorting or injecting the product and these practices pose a significant risk to the abuser that could result in overdose and death.

           A Risk Evaluation and Mitigation Strategy (REMS) is included in the label of the several medications.  A REMS is a safety strategy to manage known or potential serious risks associated with a medication and to enable patients to have continued access to such medicines by managing their safe use.  Refer to the individual product labels for details on the REMS programs.
           

          13. Risks from Concomitant Use with Benzodiazepines or other CNS Depressants: ArymoTM ER 42, Morphabond ER® 43, benzhydrocodone/acetaminophen (Apadaz®), codeine polistirex and chlorphniramine (Tuzistra XR), codeine phosphate and chlorpheniramine maleate (Tuxarin®), levorphanol, Qdolo® (tramadol), Seglentis® (tramadol/celecoxib) 

          Concomitant use of opioid with benzodiazepines or other CNS depressants may result in profound sedation, respiratory depressions, coma, and death.

          14. Life threatening respiratory depression and death have occurred in children who received codeine; most cases followed tonsillectomy and/or adenoidectomy and many of the children had evidence of being an ultra-rapid metabolizer of codeine due to a CYP2D6 polymorphism. TUXARIN ER, TUZISTRA XR are contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of TUXARIN ER, TUZISTRA XR for adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine. Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol.

          Life-threatening respiratory depression and death have occurred in children who received Qdolo® (tramadol). Some of the reported cases followed tonsillectomy and/or adenoidectomy; in at least one case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism. Qdolo® is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of Qdolo® in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol.

          15. Hepatotoxicity: benzhydrocodone/acetaminophen (Apadaz®)

          APADAZ contains acetaminophen. Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed

          4000 milligrams per day, and often involve more than one acetaminophen-containing product.


          16. Cardiovascular thrombotic events (Seglentis®)


          Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke, which can be fatal. This risk may occur early in the treatment and may increase with duration of use. SEGLENTIS is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

          17. Gastrointestinal bleeding, ulceration, and perforation (Seglentis®)

          NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms.
          Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious (GI) events.

          18. Ultra-rapid metabolism of tramadol and other risk factors for life-threatening respiratory depression in children (Seglentis®)

          Life-threatening respiratory depression and death have occurred in children who received tramadol. Some of the reported cases followed tonsillectomy and/or adenoidectomy; in at least one case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism. SEGLENTIS is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of SEGLENTIS in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol.




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          Roxybond® (oxycodone hydrochloride) [package insert]. Basking Ridge, NJ: Daiichi Sankyo, Inc. February 2022. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209777lbl.pdf. Accessed August 4, 2024.

          Levorphanol [prescribing information]. Solana Beach, CA: Sentynl Therapeutics, Inc. October 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=77f4a54a-6901-46d9-93db-ad4be7eae6c3. Accessed August 4, 2024.

          Tuxarin® (codeine phosphate and chlorpheniramine maleate) [package insert]. Irvine, CA: Nexgen Pharma, Inc. June 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206323s006lbl.pdf. Accessed August 4, 2024.

          Apadaz® (benzhydrocodone and acetaminophen) [prescribing information]. Coralville, IA: KemPharm, Inc. October 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208653s005lbl.pdf. Accessed August 4, 2024.

          Qdolo® (tramadol). Athena Bioscience, Inc. September 2020. Available at: https://qdolo.com/wp-content/uploads/2020/10/QDOLO-Prescribing-Information.pdf. Accessed August 4, 2024.

          Seglentis® (tramadol/celecoxib) [package insert]. Montgomery, AL: Kowa Pharmaceuticals America, Inc.; October 2021. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213426s000lbl.pdf. Accessed August 4, 2024

           

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          Rx.01.202 Prior Authorization Requirements for Select Drugs 

          Rx.01.33 Off-Label Use 


          Refer to table in the policy section. 
          		N/AN/A
          463
            
          		10/1/2024Rx.01.66CommercialOyenusi, OluwadamilolaQ2-2024

          BEDAQUILINE (SIRTURO®)

          Bedaquiline (Sirturo®) is indicated as part of combination therapy in adults and pediatric patients (5 years and older and weighing at least 15 kg) with pulmonary multi-drug resistant tuberculosis (MDR-TB). Reserve Sirturo® for use when an effective treatment regimen cannot otherwise be provided

          Bedaquiline (Sirturo®) is a diarylquinoline antimycobacterial drug that inhibits mycobacterial ATP synthase, an enzyme that is essential for the generation of energy in Mycobacterium tuberculosis.

          ISAVUCONAZONIUM (CRESEMBA®)

          Isavuconazonium (Cresemba®) is indicated for the treatment of invasive aspergillosis and invasive mucormycosis.

          Isavuconazonium (Cresemba®) is the prodrug of isavuconazole, an azole antifungal.  Isavuconazole inhibits the synthesis of ergosterol, a key component of the fungal cell membrane, through the inhibition of cytochrome P-450 dependent enzyme lanosterol 14-alpha-demethylase. This enzyme is responsible for the conversion of lanosterol to ergosterol. An accumulation of methylated sterol precursors and a depletion of ergosterol within the fungal cell membrane weakens the membrane structure and function.

          TEDIZOLID (SIVEXTRO®)

          Tedizolid (Sivextro®) is indicated for the treatment of adult and pediatric patients 12 years of age and older for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible bacteria.

          Tedizolid (Sivextro®) binds to the 50S bacterial ribosomal subunit. This prevents the formation of a functional 70S initiation complex that is essential for the bacterial translation process and subsequently inhibits protein synthesis. Tedizolid is bacteriostatic against enterococci, staphylococci, and streptococci.

          PRETOMANID

          Pretomanid is indicated for the treatment of adults with pulmonary extensively drug resistant (XDR) or treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB) as part of a combination regimen with bedaquiline and linezolid. Pretomanid is indicated for use in a limited and specific population of patients

           

          Pretomanid is a nitroimidazooxazine antimycobacterial drug. Pretomanid kills actively replicating M. tuberculosis by inhibiting mycolic acid biosynthesis, thereby blocking cell wall production. Under anaerobic conditions, against non-replicating bacteria, Pretomanid acts as a respiratory poison following nitric oxide release.

          OMADACYCLINE (NUZYRA®)

          NUZYRA is a tetracycline class antibacterial indicated for the treatment of adult patients with the following infections caused by susceptible microorganisms:

          • Community-acquired bacterial pneumonia (CABP)
          • Acute bacterial skin and skin structure infections (ABSSSI)

          The intent of this policy is to communicate the medical necessity criteria for bedaquiline (Sirturo®), isavuconazonium (Cresemba®), tedizolid (Sivextro®), omadacycline (Nuzyra®) and pretomanid as provided under the member's prescription drug benefit. 

          BEDAQUILINE (SIRTURO®)

          Bedaquiline (Sirturo®) is approved when ALL of the following are met:

          1. Diagnosis of pulmonary multi-drug resistant tuberculosis (MDR-TB), for which an effective treatment regimen cannot otherwise be established; and
          2. Member is 5 years of age or older and weighing at least 15kg; and
          3. Prescribed by or in consultation with an infection disease specialist or pulmonologists; and
          4. Bedaquiline is used as combination therapy as defined by ONE of the following:
            1. With at least 3 other drugs to which the member's MDR-TB isolate has been shown to be susceptible in vitro; or
            2. With at least 4 other drugs to which the patient's MDR-TB isolate is likely to be susceptible

           

          Authorization duration: 24 weeks


          ISAVUCONAZONIUM (CRESEMBA®)
          Isavuconazonium (Cresemba®) is approved when ALL of the following are met:

          1. Member is 18 years of age or older; and
          2. Prescribed by or in consultation with  an infectious diseases specialist; and 
          3. Diagnosis of ONE of the following:
            1. Treatment of invasive aspergillosis and inadequate response or inability to tolerate voriconazole; or
            2. Treatment of invasive mucormycosis

           

          Authorization duration: 12 months


          TEDIZOLID (SIVEXTRO®)
          Tedizolid (Sivextro®) is approved when ALL of the following are met:

          1. Member is 12 years of age or older; and
          2. Prescribed by or in consultation with an infectious diseases specialist; and 
          3. Documentation of use for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of Gram-positive microorganisms and ONE of the following:
            1. Inadequate response or inability to tolerate ALL antibiotics to which the organism is susceptible; or
            2. Tedizolid is the only antibiotic to which the organism is susceptible; or
            3. There is a contraindication to using an alternative antibiotic to which the organism is susceptible to (e.g., drug-drug interaction concern with the alternative antibiotic and member's existing drug regimen)

           

          Authorization duration: 4 weeks

           

          PRETOMANID

          Pretomanid is approved when ALL of the following are met:

          1. Diagnosis of pulmonary extensively drug resistant (XDR), treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB); and
          2. Medication will be used as part of combination regiment with bedaquiline (Sirturo®) and linezolid; and
          3. Member is 18 years of age or older; and
          4. Prescribed by or in consultation with an infectious disease specialist


          Authorization duration: 26 weeks

           

          OMADACYCLINE (NUZYRA®)

          Omadacycline (Nuzyra®) is approved when ALL of the following are met:

          1. Member is 18 years of age or older; and
          2. Prescribed by or in consultation with an infectious disease specialist; and
          3. One of the following:
            1. Documentation of use for the treatment of community-acquired bacterial pneumonia; or
            2. Documentation of use for the treatment of acute bacterial skin and skin structure infections (ABSSSI); and
          4.  ONE of the following:
            1. Inadequate response or inability to tolerate ALL antibiotics to which the organism is susceptible; or
            2. Omadacycline is the only antibiotic to which the organism is susceptible; or
            3. There is a contraindication to using an alternative antibiotic to which the organism is susceptible to (e.g., drug-drug interaction concern with the alternative antibiotic and member's existing drug regimen)

           

          Authorization duration: 4 weeks


          BEDAQUILINE (SIRTURO®)

          An increased risk of death was seen in the bedaquiline group (11.4%) compared with the placebo group (2.5%) in 1 placebo-controlled trial. Only use SIRTURO in patients 5 years of age and older when an effective treatment regimen cannot otherwise be provided..

          QT prolongation can occur with bedaquiline. Use with drugs that prolong the QT interval may cause addictive QT prolongation. Monitor ECGs. Discontinue SIRTURO if significant ventricular arrhythmia or QTcF interval >500 ms develops.


          Pretomanid [prescribing information]. India: Mylan, Laboratories Limited; April 2019. Available from: https://www.tballiance.org/sites/default/files/assets/Pretomanid_Full-Prescribing-Information.pdf. Accessed August 4, 2024

          Cresemba® (isavuconazonium) [package insert]. Northbrook, IL. Astellas Pharma US. December 2023.  Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8f7f73b8-586a-4df0-935f-fecd4696c16c&type=display. Accessed August 4, 2024

          Sirturo® (bedaquiline) [package insert]. Janssen Therapeutics; Titusville, NJ. October 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1534c9ae-4948-4cf4-9f66-222a99db6d0e&type=display.  Accessed August 4, 2024

          Sivextro® (tidizolid) [package insert]. White House Station, NJ: Merc and Co, Inc. March 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=75672079-589f-451a-bdbf-eaebcfcc80a9&type=display. Accessed August 4, 2024

          Nuzyra® (omadacycline) [package insert]. Boston, MA: Paratek Pharmaceutical, Inc. May 2021. Available at: https://www.nuzyra.com/nuzyra-pi.pdf. Accessed August 4, 2024


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          Rx.01.33 Off Label Use

          Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit​

          Brand NameGeneric Name
          Cresemba®isavuconazonium
          Sirturo®bedaquiline
          Sivextro®tedizolid
           Pretomanid
          Nuzyra®omadacycline

          		NANA
          464
            
          		10/1/2024Rx.01.272CommercialOyenusi, OluwadamilolaQ2-2024
          Vulvovaginal candidiasis (VVC) is one of the most common causes of vulvovaginal itching and discharge. The disorder is characterized by inflammation in the setting of Candida species. Treatment is indicated for the relief of symptoms. Recurrent vulvovaginal candidiasis (RVVC) is defined as three or more episodes of symptomatic infection within one year.

          Oteseconazole is an antifungal drug. It is an azole metalloenzyme inhibitor that inhibits the enzyme CYP51 (also known as 14α demethylase). It demethylates the 14-α position of lanosterol to yield ergosterol, a compound that plays a key role in maintaining the integrity of cell membranes in yeast and fungi, thereby inhibiting fungal growth.

          Vivjoa™ is indicated to reduce the incidence of recurrent vulvovaginal candidiasis (RVVC) in females with a history of RVVC who are NOT of reproductive potential.



          The intent of this policy is to communicate the medical necessity criteria for oteseconazole (Vivjoa™) as provided under the member's prescription drug benefit. 

          INITIAL CRITERIA: Oteseconazole (Vivjoa™) is approved when ALL of the following are met:

          1. Diagnosis of recurrent vulvovaginal candidiasis (RVVC); and
          2. Member is not of reproductive potential; and
          3. Diagnosis of RVVC is confirmed by ONE of the following:
            1. Positive potassium hydroxide (KOH) preparation; or
            2. Vaginal fungal culture; and
          4. Member has experienced 3 or more symptomatic episodes of vulvovaginal candidiasis (VVC) within the past 12 months; and
          5. Inadequate response or inability to tolerate BOTH of the following:
            1. One intravaginal product (e.g., clotrimazole, miconazole, terconazole); and
            2. Oral fluconazole

           

          Authorization duration: 4 months 


          None

          Sobel J. Candida vulvovaginitis: Treatment. UpToDate. Revised December 2022. Available from: uptodate.com. Accessed August 4, 2024

          VivjoaTM (oteseconazole) [package insert]. Durham, NC: Mycovia Pharmaceuticals, Inc; April 2022. Available at https://vivjoa.com/pi/VIVJOA-Full-Prescribing-Information.pdf. Accessed August 4, 2024


          		27/1/20246/6/202510/1/2024 1:17 AMNo presence informationsrv_ppsgw_P

          Rx.01.33 Off Label Use

          Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit​



          ​Brand Name​Generic Name
          ​Vivjoa​oteseconazole




          		NANA
          465
            
          		10/1/2024Rx.01.240CommercialOyenusi, OluwadamilolaQ2-2024

          Blepharoptosis, or ptosis of the eyelid, refers to drooping of the upper eyelid that usually results from a congenital or acquired abnormality of the muscles that elevate the eyelid. Ptosis may be the presenting sign or symptom of serious neurologic disease. Depending on the degree of ptosis, presenting symptoms may range from an asymptomatic subtle cosmetic defect to significant visual deficits. Standard of care is surgery. While effective in improving visual function and quality-of-life measures, there are risks associated with surgical intervention. The Müller muscle, an accessory smooth muscle, maintains upper eyelid elevation and is innervated by the sympathetic nervous system. Therefore, the Müller muscle is a common surgical and pharmacological target. 

          Oxymetazoline is an alpha adrenoceptor agonist targeting a subset of adrenoreceptors in Mueller's muscle of the eyelid. Oxymetazoline (Upneeq™) is indicated for the treatment of acquired blepharoptosis in adults.

          Oxymetazoline (Upneeq™), when used solely to change the appearance of any portion of the face, without improving the physiologic functioning of that portion of the body, is considered cosmetic use. 


          ​The intent of this policy is to communicate the medical necessity criteria for Oxymetazoline (Upneeq™) as provided under the member's prescription drug benefit. 

          INITAL CRITERIA: Oxymetazoline (Upneeq™) is approved when ALL of the following are met:

          1. Diagnosis of acquired blepharoptosis; and
          2. Request is not for an excluded benefit (i.e. cosmetic - solely for lifting the eyelid to improve appearance); and
          3. Member has obstructed visual field in primary gaze or down gaze due to blepharoptosis; and
          4. One of the following:
            1. Marginal reflex distance-1 (MRD-1) is less than or equal to 2mm in primary gaze; or
            2. Marginal reflex distance-1 (MRD-1) is less than or equal to 2mm in down gaze; or
            3. Superior visual field loss of at least 12 degrees or 24 percent; and
          5. Other treatable causes of blepharoptosis have been ruled out (e.g., recent botulinum toxin injection, myasthenia gravis); and
          6. Prescribed by or in consultation with an ophthalmologist or optometrist

           

          Initial authorization duration: 3 months

          REAUTHORIZATION CRITERIA: Oxymetazoline (Upneeq™) is re-approved when BOTH of the following are met:

          1. Documentation of positive clinical response to therapy (e.g., improvement in superior visual field, increase in Marginal reflex distance-1 [MRD-1]); and
          2. One of the following:
            1. Marginal reflex distance-1 (MRD-1) is less than or equal to 2mm in primary gaze; or
            2. Marginal reflex distance-1 (MRD-1) is less than or equal to 2mm in down gaze; or
            3. Superior visual field loss of at least 12 degrees or 24 percent

          Reauthorization duration: 12 months


          None

          Upneeq™ (oxymetazoline hydrochloride ophthalmic solution) [prescribing information]. Bridgewater, NJ: RVL Pharmaceuticals, Inc; May 2023. Available from: https://www.upneeq.com/Upneeq-PI.pdf. Accessed August 4, 2024

          Slonim CB, Foster S, Jaros M, et al. Association of Oxymetazoline Hydrochloride, 0.1%, Solution Administration With Visual Field in Acquired Ptosis: A Pooled Analysis of 2 Randomized Clinical Trials [published online ahead of print, 2020 Oct 1]. JAMA Ophthalmol. 2020;138(11):1168-1175. doi:10.1001/jamaophthalmol.2020.3812

          Lee, MS. Overview of ptosis. UpToDate Web site. March 2023. www.uptodate.com. Accessed August 4, 2024


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          ​Rx.01.33 Off Label Use
          Brand NameGeneric Name
          Upneeq™Oxymetazoline hydrochloride

          		NANA
          466
            
          		10/1/2024Rx.01.261CommercialOyenusi, OluwadamilolaQ2-2024

          The normal eye creates a clear image by bending (refracting) light in order to focus it onto the retina. Refractive errors occur when a component of the eye's optical system fails to focus the optical image. Presbyopia ("aging sight") is a non-refractive error that also affects visual acuity. Presbyopia occurs when the lens loses its normal accommodating power and can no longer focus on objects viewed at arm's length or closer. Approximately 128 million adults in the United States are living with presbyopia. Presbyopia has traditionally been treated with corrective lenses or surgery.

          Pilocarpine (Vuity™) is indicated for the treatment of presbyopia in adults.

          Pilocarpine hydrochloride is a cholinergic muscarinic agonist which activates muscarinic receptors located at smooth muscles such as the iris sphincter muscle and ciliary muscle. Vuity contracts the iris sphincter muscle, constricting the pupil to improve near and intermediate visual acuity while maintaining some pupillary response to light. Vuity also contracts the ciliary muscle and may shift the eye to a more myopic state.


          ​The intent of this policy is to communicate the medical necessity criteria for Pilocarpine (Vuity™) as provided under the member's prescription drug benefit. 

          INITIAL CRITERIA: Pilocarpine (Vuity™) is approved when ALL of the following are met:

          1. Diagnosis of presbyopia; and
          2. Prescribed by or in consultation with ONE of the following:
            1. Ophthalmologist; or
            2. Optometrist; and
          3. Member is unable to use corrective lenses (e.g., eyeglasses or contact lenses)


          Initial authorization duration: 1 month 

          REAUTHORIZATION CRITERIA: Pilocarpine (Vuity™) is re-approved when BOTH of the following are met:

          1. Documentation of positive clinical response to therapy (e.g., improvement in near vision in low light conditions without loss of distance vision); and
          2. Prescribed by or in consultation with one of the following:
            1. Ophthalmologist; or
            2. Optometrist

           

          Reauthorization duration: 6 months


          None

          Mian, SI. Visual impairment in adults: Refractive disorders and presbyopia. UpToDate. September 2022. Available at: https://www.uptodate.com/contents/visual-impairment-in-adults-refractive-disorders-and-presbyopia?search=presbyopia&source=search_result&selectedTitle=1~17&usage_type=default&display_rank=1. Accessed August 4, 2024

          Vuity (pilocarpine hydrochloride) [prescribing information]. North Chicago, IL: AbbVie Inc; March 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8d806897-8a2a-4518-8c68-0ec3b778de50 . Accessed August 4, 2024


          		37/1/20246/6/202510/1/2024 1:17 AMNo presence informationsrv_ppsgw_P
          ​Rx.01.33 Off Label Use
          Brand NameGeneric Name
          ​Vuity™​Pilocarpine

          		NANA
          467
            
          		10/1/2024Rx.04.5Claim Payment PolicyOyenusi, OluwadamilolaQ2-2024

          A dietary supplement is defined by the Food and Drug Administration as "a product intended for ingestion that contains a 'dietary ingredient' intended to add further nutritional value to (supplement) the diet. A 'dietary ingredient' may be one, or any combination, of the following substances:

          • a vitamin
          • a mineral
          • an herb or other botanical
          • an amino acid
          • a dietary substance for use by people to supplement the diet by increasing the total dietary intake
          • a concentrate, metabolite, constituent, or extract"

          The US Food and Drug Administration (FDA) defines a medical food as a "food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation." FDA section 5(b) of the Orphan Drug Act (21 U.S.C. 360ee (b) (3)). The FDA further defines medical foods as "foods that are specially formulated and processed (as opposed to a naturally occurring foodstuff used in a natural state) for a patient who is seriously ill or who requires use of the product as a major component of a disease or condition's specific dietary management." Medical foods are "intended for the dietary management of a patient who, because of therapeutic or chronic medical needs, has limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or who has other special medically determined nutrient requirements, the dietary management of which cannot be achieved by the modification of the normal diet alone." They also "provide nutritional support specifically modified for the management of the unique nutrient needs that result from the specific disease or condition, as determined by medical evaluation."

          Current benefit language states the plan will not cover:

          • Dietary supplements
          • Amino acid supplements
          • Medical foods (exceptions may apply; refer to benefit language for details)
          • Prescription vitamins except for pre-natal and pediatric vitamins

          The intent of this policy is to communicate the coverage of prescription vitamins, dietary supplements, and medical foods under the member’s prescription drug benefit.

          Coverage is subject to the terms, conditions, and limitations of the member's contract.

          Prescription vitamins, dietary supplements, and medical foods are not covered under the pharmacy benefit.

          An exception to allow coverage under the member's plan will be in place for prescription medication that are either mandated when used as a preventive medication as described in the Patient Protection and Affordable Care Act (PPACA) or medically necessary for the treatment of a specific illness as determined by the plan.

          The following prescription products are covered under the member's prescription benefit:

          ProductsClinical Use
          Calcitriol oralManagement of secondary hyperparathyroidism and resultant metabolic bone disease in patients with moderate to severe chronic renal failure (creatinine clearance 15 to 55 mL/min) not yet on dialysis.
          Cholecalciferol (vitamin D3) 50,000 unitsTreatment of hypoparathyroidism, refractory rickets, also known as vitamin D resistant rickets, and familial hypophosphatemia. This is an over the counter preparation included to meet essential health benefit requirements.
          Cyanocobalamin inhaledMaintenance of normal hematologic status in pernicious anemia patients who are in remission following intramuscular (IM) vitamin B12 therapy and who have no nervous system involvement
          Dialysis vitamins oral as identified by indication in product labelWasting syndrome in chronic renal failure, uremia, and impaired metabolic function of the kidney
          Doxercalciferol oralSecondary hyperparathyroidism (dialysis patients): Treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.
          Secondary hyperparathyroidism (predialysis patients): Treatment of secondary hyperparathyroidism in patients with stage 3 or 4 chronic kidney disease.
          Ergocalciferol oralTreatment of hypoparathyroidism, refractory rickets, also known as vitamin D resistant rickets, and familial hypophosphatemia.
          Paricalcitol oralHyperparathyroidism: For the prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease stage 3 and 4, and chronic kidney disease stage 5 in patients on hemodialysis or peritoneal dialysis.
          Pediatric vitaminsNutritional supplement for children
          Phytonadione oralAnticoagulant-induced prothrombin deficiency caused by coumarin or indandione derivatives.
          Coagulation disorders: Phytonadione is indicated in the following coagulation disorders which are due to faulty formation of factors II, VII, IX and X when caused by vitamin K deficiency or interference with vitamin K activity.
          Potassium aminobenzoate oralThe treatment of scleroderma, dermatomyositis, morphea, linear scleroderma, pemphigus, and Peyronie's disease.
          Prenatal vitaminsNutritional supplement used prior to conception, during pregnancy, and in the postnatal period
          Prescription electrolytesElectrolyte repleters (i.e., potassium) and electrolyte depleters (i.e., calcium acetate)

          Medical food guidance documents & regulatory information. Available from: http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/MedicalFoods/. Accessed August 4, 2024.

          Preventive Health Services. Available from: https://www.healthcare.gov/coverage/preventive-care-benefits/. Accessed August 4, 2024.

          Dietary supplements. Available from: https://www.fda.gov/food/dietarysupplements/. Accessed August 4, 2024.


          		107/1/20246/6/202510/1/2024 1:17 AMNo presence informationsrv_ppsgw_P
          Formulary Exception policy Rx.06.61
           

          Medical Foods (ie, Enteral Nutrition and Nutritional Formulas) and Low-Protein Modified Food Products 08.00.18j

          Non-FDA Approved Products Rx.04.2 

          Off-Label Use Rx. 01.33


          N/A
          		NANA
          471
            
          		10/1/2024Rx.01.182CommercialOyenusi, OluwadamilolaQ2-2024

          Irritable bowel syndrome (IBS), a common, functional gastrointestinal disorder, is defined as abdominal discomfort associated with altered bowel habits.  Three subtypes of IBS exist: IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), and mixed type (IBS-M).  Diagnosis of IBS is based solely on clinical criteria as there are no radiologic or endoscopic abnormalities in IBS and no biomarker has proven reliable for diagnosis.  Approximately 10-15% of the general adult population is affected by IBS.

          Hepatic encephalopathy (HE) is defined as brain dysfunction caused by liver insufficiency and/or portosystemic shunting.  It manifests as a wide spectrum of neurological or psychiatric abnormalities ranging from subclinical alterations to coma.

          Small Bowel Bacterial Overgrowth (SBBO)/Small Intestinal Bacterial Overgrowth (SIBO) is a condition in which the small bowel is colonized by excessive aerobic and anaerobic microbes. Therapy is typically begun after confirming SBBO/SIBO by breath test. Patients with SBBO/SIBO could present with bloating, flatulence, abdominal discomfort, or chronic watery diarrhea.

          Rifaximin (Xifaxan®), a semisynthetic antibiotic, is derived from rifampin.  It inhibits bacterial protein synthesis and growth by binding to the beta-subunit of bacterial DNA-dependent RNA polymerase, blocking one of the steps in transcription.  Rifaximin is indicated for reduction in risk of overt HE recurrence in adults, treatment of IBS-D in adults, and Small Bowel Bacterial Overgrowth (SBBO)/Small Intestinal Bacterial Overgrowth (SIBO).  When treating IBS-D, the course of therapy is 14 days.  The regimen may be repeated up to 2 times.   


          The intent of this policy is to communicate the medical necessity criteria for rifaximin (Xifaxan®) as provided under the member’s prescription drug benefit.

          Hepatic disease with risk of hepatic encephalopathy

          INITIAL CRITERIA: Rifaximin (Xifaxan®) 550 mg is approved when BOTH of the following are met:

          1. Diagnosis of hepatic disease with risk for hepatic encephalopathy (i.e., previous episode of hepatic encephalopathy, advanced liver disease, hepatocellular carcinoma); and
          2. Member is 18 years of age or older; and
          3. Inadequate response or inability to tolerate lactulose

           

          Initial authorization duration: 2 years (Maximum daily dose 2/day)

          REAUTHORIZATION CRITERIA Rifaximin (Xifaxan®) 550mg is re-approved when there is documentation of positive clinical response to therapy.

          Reauthorization duration: 2 years (Maximum daily dose 2/day)

          ________________________________________________________________________________________
          Irritable Bowel Syndrome with Diarrhea

          INITIAL CRITERIA: Rifaximin (Xifaxan®) 550mg is approved when All of the following are met:

          1. Diagnosis of irritable bowel syndrome- diarrhea; and
          2. Inadequate response or inability to tolerate an antispasmodic; and
          3. Member is 18 years of age or older; and
          4. Member does not exceed 3 courses (42 days) of therapy

          Initial authorization duration: 3 months (max of 14 days/84 days; Maximum daily dose 3/day)

          REAUTHORIZATION CRITERIA: Rifaximin (Xifaxan®) 550mg is re-approved when ALL of the following are met:

          1. Diagnosis of irritable bowel syndrome – diarrhea; and
          2. Symptoms of Irritable Bowel Syndrome continue to persist; and
          3. Member demonstrates positive clinical response to therapy as evidenced by both of the following:
            1. Improvement in abdominal pain; and
            2. Reduction in the Bristol Stool Scale; and
          4. Inadequate response or inability to tolerate an antispasmodic; and
          5. BOTH of the following:
            1. Member does not exceed 3 courses (42 days) of therapy; and
            2. No documentation of rifaximin (Xifaxan®) treatment within the last 10 weeks.

          Reauthorization duration: 3 months (max of 14 days/84 days; Maximum daily dose 3/day)

          ___________________________________________________________________________________________

          Small Bowel Bacterial Overgrowth (SBBO)/Small Intestinal Bacterial Overgrowth (SIBO)

          INITIAL CRITERIA: Rifaximin (Xifaxan®) 550mg is approved when ALL of the following are met:

          1. Diagnosis of Small Bowel Overgrowth (SBBO)/Small Intestinal Bacterial Overgrowth (SIBO); and
          2. Inadequate response or inability to tolerate two of the following antibiotics:
            1. Neomycin; or
            2. Amoxicillin/clavulanic acid (Augmentin); or
            3. Ciprofloxacin (Cipro); or
            4. Trimethoprim-sulfamethoxazole (Bactrim); or
            5. Doxycycline (Vibramycin) or minocycline (Minocin) or tetracycline; or
            6. Metronidazole (Flagyl); or
            7. Cephalexin (Keflex)

          Initial authorization duration: 3 months (Maximum daily dose 3/day)

          REAUTHORIZATION CRITERIA: Rifaximin (Xifaxan®) 550mg is re-approved when all of the following are met:

          1. Diagnosis of Small Bowel Overgrowth (SBBO)/Small Intestinal Bacterial Overgrowth (SIBO); and
          2. Member demonstrates positive clinical response to therapy (e.g., resolution of symptoms); and
          3. Member experiences relapse with Xifaxan discontinuation

          Reauthorization duration: 3 months (Maximum daily dose 3/day)


          None

          American Association for the Study of Liver Diseases and European Association for the Study of the Liver. Hepatic Encephalopathy in Chronic Liver Disease: 2014 Practice Guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. Journal of Hepatology. Available from: http://www.easl.eu/medias/cpg/Hepatic-Encephalopathy-Chronic-Liver-Disease/English-report.pdf. Accessed August 4, 2024.

          Ford AC, Moayyedi P, Lacy, BE, et al. American College of Gastroenterology Monograph on the Management of Irritable Bowel Syndrome and Chronic Idiopathic Constipation. Am J Gastroenterol. 2014: 109:S2-S26; doi: 1001038/ajg.2014.187

          Weinberg DS, Smalley W, Heidelbaugh JJ, et al. American Gastroenterological Association Institute Guideline on the Pharmacological Management of Irritable Bowel Syndrome. Gastroenterology. 2014; 147(5):1146-48.

          Xifaxan® (rifaximin) [prescribing information]. Bridgewater, NJ: Salix Pharmaceuticals; September 2022. Available from: https://shared.salix.com/shared/pi/xifaxan550-pi.pdf. Accessed August 4, 2024.

          Pimentel M. Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, February 2022. Accessed August 4, 2024.

           


          		137/1/20246/6/202510/1/2024 1:18 AMNo presence informationsrv_ppsgw_P
          Off-Label Use Rx.01.33
          Brand Name
          		​Generic Name
          ​Xifaxan®
          		​Rifaximin

          		NANA
          472
            
          		10/1/2024Rx.01.215CommercialOyenusi, OluwadamilolaQ2-2024

          Hereditary transthyretin amyloidosis (hATTR) is a rare autosomal dominant, progressively debilitating, and often fatal genetic disease characterized by the accumulation of abnormal amyloid protein in tissues. Transthyretin (TTR) is produced primarily by the liver and is responsible for the transport of thyroxine and retinol binding protein-vitamin A complex. The hATTR genetic mutations lead to mutated TTR protein which results in destabilization from the TTR tetramer into monomers and oligomers, protein misfolding, and aggregation resulting in formation of TTR amyloid fibrils.   hATTR can present with peripheral and/or autonomic neuropathy, infiltrative cardiomyopathy, vitreous amyloid, or leptomenigeal disease.

          Inotersen (Tegsedi™) is an antisense oligonucleotide that causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.

          Inotersen (Tegsedi™) is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.  

          Transthyretin-mediated amyloidosis with cardiomyopathy (ATTR-CM) occurs when amyloidosis occurs in the cardiac tissue.  Wild type ATTR-CM typically presents in men aged 65 years and older, but it can occur in women and in younger patients. Amyloid accumulates in the cardiac tissue leading to atrial and ventricular wall thickening and diastolic dysfunction, arrhythmias, and preserved ejection fraction heart failure.  For wild type ATTR-CM, the median survival is reported to be 3.6 years.

           

          Patients with wild type ATTR may also present with bilateral carpal tunnel syndrome as an initial symptom years before the onset of cardiac symptoms (Sekijima 2015).

          Due to the lack of effective therapy, testing for ATTR-CM has been underutilized. Testing may include echocardiogram, cardiac magnetic resonance imaging (MRI), and nuclear scintigraphy. Tissue biopsy, either endomyocardial tissue or other locations such as abdominal fat pad, is the gold standard for diagnosis of amyloidosis. A non-invasive test to identify those with ATTR-CM is radiotracer 99mtechnetium pyrophosphate scan (99mTc-PYP). The FDA-has not yet approved 99mTc-PYP test for the diagnosis of ATTR-CM, but it is being used in clinical practice (Vyndaqel Dossier 2019).

          Tafamidis meglumine (Vyndaqel®, Vyndamax ®) is a selective transthyretin (TTR) stabilizer, limiting the dissociation of the native TTR tetramer into monomers, which reduces TTR amyloid fibril formation.

          Tafamidis meglumine (Vyndaqel®, Vyndamax ®) is indicated for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. 

          Eplontersen is an antisense oligonucleotide-GalNAc conjugate that causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.

          WAINUA is a transthyretin-directed antisense oligonucleotide indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.



          ​The intent of this policy is to communicate the medical necessity criteria for inotersen (Tegsedi) ), tafamidis meglumine (Vyndamax®, Vyndaqel®), eplontersen (Wainua) as provided under the member's prescription drug benefit.

          INITIAL CRITERIA Tegsedi™ (inotersen) is approved when ALL of the following are met:

          1. Diagnosis of polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis with transthyretin mutation (e.g., V30M) confirmed by molecular genetic testing; and
          2. Documentation of ONE of the following baseline ambulation parameters in either the Familial Amyloid Polyneuropathy (FAP) Stage or Polyneuropathy Disability (PND) Score
            1. Stage 1 (unimpaired ambulation) or 2 (assisted ambulation) on the Familial Amyloid Polyneuropathy (FAP) staging tool; or
            2. Score I, II, IIIa, or IIIb on the Polyneuropathy Disability (PND) scoring tool; AND
          3. Documented presence of cardiac or renal manifestations, or motor, sensory, or autonomic neuropathy related to the hATTR amyloidosis with polyneuropathy (e.g., neuropathic pain, muscle weakness that affects daily living, orthostatic hypotension, diarrhea, nausea, vomiting, heart failure, arrhythmias, proteinuria, renal failure; vision disorders, such as vitreous opacity, dry eyes, glaucoma, or pupils with an irregular or scalloped appearance; and
          4. Documentation confirming the member has not had a liver transplant; and
          5. Prescribed by or in consultation with a neurologist, geneticist, or professional provider specializing in the treatment of amyloidosis; and
          6. Member is 18 years of age or older; and
          7. No concurrent use with another TTR silencer (e.g., patisiran (Onpattro), vutrisiran (Amvuttra), eplontersen (Wainua)) or with a TTR stabilizer (e.g., Vyndaqel, Vyndamax)

           

          Initial authorization duration: 16 months


          CONTINUATION CRITERIA Tegsedi™ (inotersen) is re-approved when BOTH of the following are met:

          1. Documentation of one of the following
            1. Stage 1 (unimpaired ambulation) or 2 (assisted ambulation) on the Familial Amyloid Polyneuropathy (FAP) staging tool; or
            2. Score I, II, IIIa, or IIIb on the Polyneuropathy Disability (PND) scoring tool; and
          2. Documented improvement or stability in the signs and symptoms hATTR amyloidosis with polyneuropathy (e.g., neuropathic pain, muscle weakness that affects daily living, orthostatic hypotension, diarrhea, nausea, vomiting, heart failure, arrhythmias, proteinuria, renal failure; vision disorders, such as vitreous opacity, dry eyes, glaucoma, or pupils with an irregular or scalloped appearance), based on objective or standard evaluation scales; and
          3. No concurrent use with another TTR silencer (e.g., patisiran (Onpattro), vutrisiran (Amvuttra), eplontersen (Wainua)) or with a TTR stabilizer (e.g., Vyndaqel, Vyndamax)

          Continuation authorization duration: 2 years

          INITIAL CRITERIA Tafamidis meglumine (Vyndamax®, Vyndaqel®) is approved when ALL of the following are met:

          1. Member is 18 years of age or older; and
          2. Diagnosis of transthyretin-mediated amyloidosis with cardiomyopathy (ATTR-CM) confirmed by ONE of the following:
            1. Member has a transthyretin (TTR) mutation (e.g., V122I), or
            2. Cardiac or noncardiac tissue biopsy demonstrating histologic confirmation of TTR amyloid deposits, or
            3. All of the following: echocardiogram or cardiac magnetic resonance image suggestive of amyloidosis, scintigraphy scan suggestive of cardiac TTR amyloidosis, and absence of light-chain amyloidosis; and
          3. Prescribed by or in consultation with a cardiologist; and
          4. One of the following:
            1. History of heart failure (HF), with at least one prior hospitalization for HF, or
            2. Presence of clinical signs and symptoms of HF (e.g., dyspnea, edema); or
          5. Member has New York Heart Association (NYHA) Functional Class I, II, or III heart failure; and
          6. No concurrent use with a TTR silencer (e.g., patisiran (Onpattro), vutrisiran (Amvuttra), eplontersen (Wainua), inotersen (Tegsedi))

          Initial authorization duration: 12 months

          REAUTHORIZATION CRITERIA: Tafamidis meglumine (Vyndamax®, Vyndaqel®) is re-approved when ALL of the following are met:

          1. Positive clinical response to therapy; and
          2. Member continues to have NYHA Functional Class I, II, or III heart failure; and
          3. Prescribed by or in consultation with a cardiologist; and
          4. No concurrent use with a TTR silencer (e.g., patisiran (Onpattro), vutrisiran (Amvuttra), eplontersen (Wainua), inotersen (Tegsedi))

          Reauthorization duration: 12 months

          INITIAL CRITERIA: Eplontersen (Wainua™) is approved when ALL of the following are met:

          1. Diagnosis of hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) with polyneuropathy; and
          2. Member is 18 years of age or older; and
          3. Member has a transthyretin (TTR) mutation (e.g., V30M); and
          4. One of the following:
            1. Member has a baseline familial amyloidotic polyneuropathy (FAP) stage of 1 or 2; or
            2. Member has a baseline neuropathy impairment score (NIS) greater than or equal to 10 and less than or equal to 130; or
            3. Member has a baseline Karnofsky Performance Status score greater than 50%; and
          5. Presence of clinical signs and symptoms of the disease (e.g., neuropathy); and
          6. Member has not had a liver transplant; and
          7. Prescribed by or in consultation with a neurologist; and
          8. No concurrent use with another TTR silencer (e.g., patisiran (Onpattro), vutrisiran (Amvuttra), inotersen (Tegsedi)) or with a TTR stabilizer (e.g., Vyndaqel, Vyndamax)

          Initial authorization duration: 12 months

          CONTINUATION CRITERIA: Eplontersen (Wainua™) is re-approved when ALL of the following are met:

          1. Member demonstrates positive clinical response to therapy as evidenced by an improvement in clinical signs and symptoms from baseline (e.g., neuropathy, quality of life, lower serum TTR level); and
          2. One of the following:
            1. Member continues to have a familial amyloidotic polyneuropathy (FAP) stage of 1 or 2; or
            2. Member continues to have a neuropathy impairment score (NIS) greater than or equal to 10 and less than or equal to 130; or
            3. Member continues to have a Karnofsky Performance Status score greater than 50%; and
          3. Member has not had a liver transplant; and
          4. Prescribed by or in consultation with a neurologist; and
          5. No concurrent use with another TTR silencer (e.g., patisiran (Onpattro), vutrisiran (Amvuttra), inotersen (Tegsedi)) or with a TTR stabilizer (e.g., Vyndaqel, Vyndamax)

          Continuation approval duration: 12 months


          ​WARNING: THROMBOCYTOPENIA AND GLOMERULONEPHRITIS

          Thrombocytopenia

          • TEGSEDI causes reductions in platelet count that may result in sudden and unpredictable thrombocytopenia, which can be life-threatening.
          • Testing prior to treatment and monitoring during treatment is required

          Glomerulonephritis
          • TEGSEDI can cause glomerulonephritis that may require immunosuppressive treatment and may result in dialysis-dependent renal failure.
          • Testing prior to treatment and monitoring during treatment is required

          Gorevic PD. Genetic factors in the amyloid diseases. UpToDate Web site. Updated December 18, 2018. Available from: http://www.uptodate.com/. Accessed August 4, 2024.

          Grogan M, Scott CG, Kyle RA, et al. Natural history of wild type transthyretin cardiac amyloidosis and risk stratification using a novel staging system. J Am Coll Cardiol. 2016;68:1014-1020.

          Hawkins PN, Ando Y, Dispenzeri A, et al. Evolving landscape in the management of transthyretin amyloidosis. Ann Med. 2015;47:625-638.

          Klaassen SHC, Tromp J, Nienhuis HLA, et al. Involvement at presentation in hereditary transthyretin-derived amyloidosis and the value of N-terminal pro-B-type natriuretic peptide. Am J Cardiol. 2018;121:107-112.

          Maurer MS, Grogan DR, Judge DP, et al. Tafamidis in transthyretin amyloid cardiomyopathy. Effects on transthyretin stabilization and clinical outcomes. Circ Heart Fail. 2015;8:519-526.

          Maurer MS, Hanna M, Grogan M, et al. Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016;68(2):161-172.

          Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379:1007-1016.

          Fontana M. Cardiac amyloidosis: Epidemiology, clinical manifestations, and diagnosis. UpToDate Web site. Updated August 2022. Available from: https://www.uptodate.com/contents/cardiac-amyloidosis-clinical-manifestations-and-diagnosis?search=clinical-manifestations-and-diagnosis-of-amyloid-cardiomyopathy&source=search_result&selectedTitle=1~80&usage_type=default&display_rank=1. Accessed August 4, 2024.

          Merlini G, Planté-Bordeneuve V, Judge DP, et al. Effects of tafamidis on transthyretin stabilization and clinical outcomes in patients with non-Val30Met transthyretin amyloidosis. J Cardiovasc Trans Res. 2013;6:1011-1020.

          Mundayat R, Steward M, Alvir J, et al. Positive effectiveness of tafamidis in delaying disease progression in transthyretin familial amyloid polyneuropathy up to 2 years: an analysis from the Transthyretin Amyloidosis Outcomes Survey (THAOS) Neurol Ther. 2018;7:87-101.

          Nativi-Nicolau J, Maurer MS. Amyloidosis cardiomyopathy: update in diagnosis and treatment of the most common types. Curr Opin Cardiol. 2018;33(5):571-579.

          Pfizer Press Release. FDA issues complete response letter for Pfizer's tafamidis meglumine new drug application. https://investors.pfizer.com/investor-news/press-release-details/2012/FDA-Issues-Complete-Response-Letter-For-Pfizers-Tafamidis-Meglumine-New-Drug-Application/default.aspx. June 18, 2012. Accessed August 4, 2024.

          Plante-Bordeneuve V. Update in the diagnosis and management of transthyretin familial amyloid polyneuropathy. J Neurol. 2014;261:1227-1233.

          Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129-2200.

          Seferović PM, Polovina M, Bauersachs J, et al. Heart failure in cardiomyopathies: a position paper from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2019;21:553-576.

          Sekijima Y. Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments. J Neurol Neurosurg Psychiatry. 2015;86:1036-1043.

          Siddiqi OK, Ruberg FL. Cardiac amyloidosis: an update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med. 2018;28:10-21.

          Tegsedi™ (inotersen) [prescribing information]. Boston MA. Akcea Therapeutics, Inc. June 2022. Available at: https://tegsedi.com/wp-content/uploads/2018/10/prescribing-information.pdf. Accessed August 4, 2024.

          Vyndaqel and Vyndamax (tafamidis, tafamidis meglumine )[prescribing information]. New York, NY: Pfizer Pharmaceuticals, Inc. April 2023. Available from: labeling.pfizer.com/ShowLabeling.aspx?id=11685. Accessed August 4, 2024.

          Wainua (eplontersen) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP. December 2023. Available at: WAINUA Full Prescribing Information (den8dhaj6zs0e.cloudfront.net). Accessed August 4, 2024. 


          		87/1/20246/6/202510/1/2024 1:18 AMNo presence informationsrv_ppsgw_P
          Off-Label Use Rx.01.33
          Brand NameGeneric Name
          Tegsedi™Inotersen
          Vyndamax®, Vyndaqel®Tafamidis meglumine
          Wainua™eplontersen

          		N/AN/A
          474
            
          		10/1/2024Rx.01.45CommercialOyenusi, OluwadamilolaQ2-2024
          Intranasal steroids are used for a variety of disorders including nasal polyps, non-allergic rhinitis, perennial allergic rhinitis and seasonal allergic rhinitis.  

          Intranasal steroids provide anti-inflammatory effects on the nasal mucosa. Their exact mechanism is unknown but corticosteroids have been shown to have a wide range of actions on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation.  

          The intent of this policy is to communicate the medical necessity criteria for beclomethasone (Beconase AQ®), fluticasone propionate (Xhance™), beclomethasone (Qnasl®/ Qnasl®Children's), azelastine hydrochloride and fluticasone propionate (Dymista®), and olopatadine hydrochloride and mometasone furoate (Ryaltris®) as provided under the member's prescription drug benefit. 



          ​Nasal polyps

          INITIAL CRITERIA: Beconase AQ®, or fluticasone propionate (Xhance™) is approved when BOTH of the following are met:

          1. Diagnosis of nasal polyps; and
          2. Submission of documentation (e.g., chart note) or paid claim history showing inadequate response or inability to tolerate generic fluticasone propionate (trial for at least 90 days within the previous 365 days) 

          Initial authorization duration: 2 years

          REAUTHORIZATION CRITERIA: Beconase AQ®, or fluticasone propionate (Xhance®) is reapproved when there is documentation of positive clinical response to therapy.

          Reauthorization duration: 2 years

          Allergic Rhinitis
          INITIAL CRITERIA: Beconase AQ®, Children's Qnasl®*, azelastine hydrochloride and fluticasone propionate (Dymista), Qnasl®, or Ryaltris® is approved when BOTH of the following are met:

          1. Diagnosis of allergic rhinitis; and
          2. Inadequate response or inability to tolerate BOTH of the following generic nasal sprays:
            1. Flunisolide; and
            2. Fluticasone propionate

          Initial authorization duration: 2 years

          REAUTHORIZATION CRITERIA: Beconase AQ®, Children's Qnasl®*, azelastine hydrochloride and fluticasone propionate (Dymista®), Qnasl®, or Ryaltris® is re-approved when there is documentation of positive clinical response to therapy.
          Reauthorization duration: 2 years

          *Fluticasone propionate is approved for children under 6 years of age

          Chronic rhinosinusitis without nasal polyps

          INITIAL CRITERIA: Fluticasone propionate (Xhance™) is approved when BOTH of the following are met:

          1. Diagnosis of chronic rhinosinusitis without nasal polyps; and
          2. Submission of documentation (e.g., chart notes) or paid claim history showing inadequate response or inability to tolerate generic fluticasone propionate (trial of at least 90 days within the previous 365 days)

          Initial authorization duration: 2 years


          REAUTHORIZATION CRITERIA: Fluticasone propionate (Xhance™) is re-approved with documentation of positive clinical response to therapy
           

          Reauthorization duration: 2 years


          None

          Beconase AQ (beclomethasone dipropionate) [package insert]. Research Triangle Park, NC. GlaxoSmithKline. April 2019. https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Beconase_AQ/pdf/BECONASE-PI-PIL.PDF Accessed August 4, 2024.

          Dymista (azelastine hydrochloride and fluticasone propionate) [package insert]. Somerset, NJ. Meda Pharmaceutical. September 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/202236s008lbl.pdf. Accessed August 4, 2024.

          Qnasl® (beclomethasone) [package insert]. Northridge, CA. Teva Respiratory, LLC. March 2018.  Available at: http://qnasl.com/Content/pdf/pi.pdf Accessed August 4, 2024.

          Ryaltris® (olopatadine hydrochloride and mometasone furoate monohydrate nasal spray) [package insert]. Columbus, OH: Hikma Specialty USA Inc. January 2022. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=382eac74-a7ce-4f42-ac0a-b253308f335f. Accessed August 4, 2024.

          Seidman MD et al. Clinical practice guideline: allergic rhinitis executive summary. Otolaryngol Head Neck Surg. 2015 Feb; 152(2): 197-206.

          Wallace DV et al. Pharmacologic treatment of seasonal allergic rhinitis: synopsis of guidance from the 2017 Joint Task Force on practice parameters. Ann Intern med. 2017 Dec 19; 167(12):867-881

          Peters AT et al. Diagnosis and management of rhinosinusitis: a practice parameter update. Ann Allergy Asthma Immunol. 2014 Oct; 113(4): 347-85.

          Xhance (fluticasone propionate) [prescribing information]. Yardley, PA: OptiNose US. Inc. March 2024. Availabel at: Approval [Rx ONLY] (xhance.com). Accessed August 4, 2024. 
          . 

           

          		267/1/20243/14/202510/1/2024 1:18 AMNo presence informationsrv_ppsgw_P
          Rx.01.33 Off-Label Use 
          Beconase AQ®beclomethasone
          Dymista®azelactine hydrochloride and fluticasone propionate
          Qnasl®beclomethasone dipropionate
          Qnasl®Childrensbeclomethasone dipropionate
          Xhance™Fluticasone propionate
          Ryaltris®olopatadine hydrochloride and mometasone furoate monohydrate

          		Xhance® fluticasone propionate
          475
            
          		10/1/2024Rx.01.257CommercialOyenusi, OluwadamilolaQ2-2024
          Alagille syndrome (AGS), also known as arteriohepatic dysplasia, is a multisystem autosomal dominant disorder that largely affects the liver. Alagille syndrome causes intractable pruritus and disfiguring xanthomas because of retained bile acids and cholesterol. Pruritus is a common symptom in patients with ALGS and the pathophysiology of pruritus in patients with ALGS is not completely understood.

          Maralixibat is a reversible inhibitor of the ileal bile acid transporter (IBAT). It decreases the reabsorption of bile acids (primarily the salt forms) from the terminal ileum. Although the complete mechanism by which maralixibat improves pruritus in ALGS patients is unknown, it may involve inhibition of the IBAT, which results in decreased reuptake of bile salts, as observed by a decrease in serum bile acids.

          Maralixibat (Livmarli®​) is indicated for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) 3 months of age and older. It is also indicated for the treatment of cholestatic pruritus in patients 5 years of age and older with progressive familial intrahepatic cholestasis (PFIC)

          The intent of this policy is to communicate the medicalnecessity criteria for Maralixibat (Livmarli®) as provided under the member's prescription drug benefit.

          ​

          Alagille Syndrome (ALGS)

          INITIAL CRITERIA Maralixibat (Livmarli®) is approved when ALL of the following are met:

          1. Diagnosis of Alagille Syndrome (ALGS) as confirmed by BOTH of the following:
            1. Molecular genetic testing confirms mutations in the JAG1 or NOTCH2 gene; and
            2. One of the following:
              1. Total serum bile acid > 3x the upper limit of normal (ULN); or
              2. Conjugated bilirubin > 1 mg/dL; or
              3. Fat soluble vitamin deficiency otherwise unexplainable; or
              4. Gamma-glutamyl transpeptidase (GGT) > 3x ULN; and
          2. Member is experiencing moderate to severe cholestatic pruritus; and
          3. Member is 3 months of age or older; and
          4. Prescribed by or in consultation with a hepatologist or gastroenterologist; and
          5. Member has had an inadequate response or inability to tolerate at least two of the following treatments used for the relief of pruritus:
            1. Ursodeoxycholic acid (e.g., Ursodiol); or
            2. Antihistamines (e.g., diphenhydramine, hydroxyzine); or
            3. Rifampin; or
            4. Bile acid sequestrants (e.g., cholestyramine, colestipol, colesevelam)

          Initial authorization duration: 6 months

          REAUTHORIZATION CRITERIA Maralixibat (Livmarli™) is re-approved with documentation of positive clinical response to therapy (e.g., reduced bile acids, reduced pruritus severity score)
          Reauthorization duration: 2 years

          Progressive Familial Intrahepatic Cholestasis (PFIC)

          INITIAL CRITERIA: Maralixibat (Livmarli™) is approved when ALL of the following are met:

          1. Both of the following:
            1. Diagnosis of Progressive familial intrahepatic cholestasis (PFIC); and
            2. Molecular genetic testing confirms mutations in the ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, or MYO5B; and
          2. Member is experiencing both of the following:
            1. Moderate to severe pruritus; and
            2. Member has a serum bile acid concentration above the upper limit of the normal reference for the reporting laboratory; and
          3. Member is 5 years of age or older; and
          4. Member has had an inadequate response to at least two of the following treatments used for the relief of pruritus:
            1. Ursodeoxycholic acid (e.g., Ursodiol)
            2. Antihistamines (e.g., diphenhydramine, hydroxyzine)
            3. Rifampin
            4. Bile acid sequestrants (e.g., Questran, colestid, Welchol); and
          5. Prescribed by or in consultation with one of the following:
            1. Hepatologist; or
            2. Gastroenterologist

          Initial authorization duration: 6 months

          REAUTHORIZATION CRITERIA: Maralixibat (Livmarli™) is re-approved with documentation of positive clinical response to therapy (e.g., reduced serum bile acids, improved pruritus)

          Reauthorization duration: 2 years


          None
          Wehrman A, Loomes KM. Causes of cholestasis in neonates and young infants. UpToDate. July 2023. Available at: https://www.uptodate.com. Accessed August 4, 2024

          Ben Ameur, S.; Chabchoub, I.; Telmoudi, J.; Belfitouri, Y.; Rebah, O.; Lacaille, F.; Aloulou, H.; Mehrzi, A.; Hachicha, M. (2016). Management of cholestatic pruritus in children with Alagille syndrome: Case report and literature review. Archives de Pédiatrie, 23(12), 1247–1250. doi:10.1016/j.arcped.2016.09.004

          Livmarli® (maralixibat) [package insert]. Foster City, CA. Mirum Pharmaceuticals Inc. March 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=64000394-1ef6-4e76-8ba8-11f25ba1b167. Accessed August 4, 2024



          		57/1/202412/18/202410/1/2024 1:19 AMNo presence informationsrv_ppsgw_P
          Rx.01.33 Off Label Use
          Brand NameGeneric Name
          Livmarli™maralixibat

          		Livmarli® maralixibat
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