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525
  
1/1/2025Rx.01.297CommercialVanHorn, LynnseyQ3-2024
Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin condition that can be life-threatening if untreated. It is characterized by recurrent, widespread eruptions of painful, sterile pustules which is generally accompanied by fever, chills, headache, rapid pulse rate, loss of appetite, nausea and muscle weakness. The severity of GPP flares can vary, relapses are common. GPP is a distinct disease from other forms of psoriasis such as plaque psoriasis. Spesolimab-sbzo (Spevigo) is the first FDA approved treatment for GPP. 

Spesolimab-sbzo is a humanized monoclonal immunoglobulin G1 antibody that inhibits interleukin-36 (IL-36) signaling by specifically binding to the IL36R. Binding of spesolimab-sbzo to IL36R prevents the subsequent activation of IL36R by its ligands (IL-36 α, β and γ) and downstream activation of pro-inflammatory and pro-fibrotic pathways. The precise mechanism linking reduced IL36R activity and the treatment of flares of GPP is unclear.

SPEVIGO is an interleukin-36 receptor antagonist indicated for the treatment of generalized pustular psoriasis (GPP) in adults and pediatric patients 12 years of age and older and weighing at least 40 kg.

Spevigo SQ in used for treatment of GPP when the patient is not experiencing a flare and it is given after IV loading dose. Only Spevigo IV is used for treatment of GPP flare. 



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

INITIAL CRITIERIA: Spesolimab-sbzo (Spevigo®) is medically necessary when ALL of the following are met:

  1. Diagnosis of generalized pustular psoriasis (GPP) as defined by both of the following:
    1. Primary, sterile, macroscopically visible pustules on non-acral skin (excluding cases where pustulation is restricted to psoriatic plaques); and
    2. Disease is relapsing (>1 episode) or persistent (>3 months); and
  2. Subcutaneous formulation will not be used to treat GPP flare; and
  3. Both of the following:
    1. Member is 12 years of age or older; and
    2. Member weighs at least 40 kg; and
  4. Prescribed by or in consultation with a dermatologist

Initial authorization duration: 12 months

REAUTHORIZATION CRITERIA: Spesolimab-sbzo (Spevigo®) is re-approved with documentation of positive clinical response to therapy (e.g., reduction in the number of flares)

Reauthorization duration: 12 months


None

Genetic and Rare Disease Information Center. Generalized pustular psoriasis. Updated September 2024. Available at: https://rarediseases.info.nih.gov/diseases/12819/generalized-pustular-psoriasis. Assessed October 17, 2024

Spevigo (spesolimab-sbzo) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. March 2024. Available at: Prescribing Information (boehringer-ingelheim.com). Accessed October 17, 2024. 


19/12/20249/11/20251/1/2025 1:19 AMNo presence informationsrv_ppsgw_P
​Off-Label Use Rx.01.33
​Brand Name​Generic Name
​Spevigo® SQ​Spesolimab-sbzo

SPEVIGO      INJ 150/1MLSPESOLIMAB-SBZO SUBCUTANEOUS SOLN PREF SYR 150 MG/ML
485
  
1/1/2025Rx.01.87CommercialVanHorn, LynnseyQ3-2024

Parathyroid hormone (PTH) and calcitriol are the two major hormones that regulate calcium and phosphate homeostasis.  PTH maintains serum ionized calcium concentrations in a narrow range by stimulating renal tubular calcium reabsorption and bone resorption.  Chronic exposure to high PTH results in bone resorption, however intermittent administration of recombinant human PTH stimulates bone formation to a greater extent than resorption, at least over the first 12 months of therapy.  While PTH is an effective treatment for osteoporosis, it is generally not a first line drug due to route of administration (subcutaneous), long-term safety concerns, and availability of other agents.

Teriparatide is recombinant human PTH. Abaloparatide is a human parathyroid hormone related peptide (PTHrP(1-34)).

 Teriparatide (Forteo®) is indicated:

  • For the treatment of postmenopausal women with osteoporosis who are at high risk for fracture. These include women with a history of osteoporotic fracture, or who have multiple risk factors for fracture, or who have failed or are intolerant of previous osteoporosis therapy, based upon physician assessment.
  • To increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. These include men with a history of osteoporotic fracture, or who have multiple risk factors for fracture, or who have failed or are intolerant to previous osteoporosis therapy, based upon physician assessment.
  • For treatment of osteoporosis associated with sustained systemic glucocorticoid therapy at high risk fracture.

Abaloparatide (Tymlos™) is indicated: 
  • For the treatment of postmenopausal women with osteoporosis at high risk of fracture or patients who have failed or are intolerant to other available osteoporosis therapy.
  • For the treatment to increase bone density in men with osteoporosis at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy.
The intent of this policy is to communicate the medical necessity criteria for abaloparatide (Tymlos™) and teriparatide (Forteo®) as provided under the member's prescription drug benefit. 


Primary or hypogonadal osteoporosis in men and Glucocorticoid-induced osteoporosis in men or women

INITIAL CRITERIA: Teriparatide (Forteo®) is medically necessary when ALL of the following are met:

  1. The member is 18 years of age or older; and
  2. ONE of the following:
    1. Primary or hypogonadal osteoporosis in men; or
    2. Glucocorticoid-induced osteoporosis in men or women (daily dose greater than or equal to 5mg prednisone or equivalent for at least 3 months); and
  3. ONE of the following:
    1. Member is high risk for fracture defined by ONE of the following:
      1. History of osteoporotic fractures (low-trauma fracture of the hip, spine, proximal humerus, pelvis, or distal forearm); or
      2. At least two risk factors for a fracture (e.g., endocrine disorders, gastrointestinal disorders, use of medications associated with low bone mass or bone loss such as corticosteroids); or
      3. Member has a T score of at least -2.5 standard deviations below the young adult mean (T-score ≤ -2.5); or
    2. Inadequate response or inability to tolerate ONE of the following osteoporosis therapies:
      1. Bisphosphonates; or
      2. Hormone replacement therapy; or
      3. Selective estrogen receptor modulators (SERMs); or
      4. Calcitonin salmon (Miacalcin); or
      5. Denosumab (Prolia); and
  4. For Forteo® only, inadequate response or inability to tolerate Teriparatide® manufactured by Alvogen

Initial Authorization duration: 12 months

REAUTHORIZATION CRITERIA: Teriparatide (Forteo®) is medically necessary when BOTH of the following are met:

  1. Documentation of positive clinical response; and
  2. ONE of the following:
    1. Cumulative lifetime therapy does not exceed 2 years; or
    2. For Forteo® only, member remains at or has returned to having a high risk for fracture despite a total of 24 months of use for parathyroid hormones

Reauthorization duration: 12 months

Postmenopausal osteoporosis

INITIAL CRITERIA: Abaloparatide (Tymlos™) or teriparatide (Forteo®) is medically necessary when ALL of the following are met:

  1. The member is 18 years of age or older; and
  2. Diagnosis of postmenopausal osteoporosis; and
  3. ONE of the following:
    1. Member is high risk for fracture defined by ONE of the following:
      1. Member has a T score of at least -2.5 standard deviation below the young adult mean (T-score ≤ -2.5); or
      2. History of osteoporotic fractures (low-trauma fracture of the hip, spine, proximal humerus, pelvis, or distal forearm); or
      3. At least two risk factors for a fracture (e.g., endocrine disorders, gastrointestinal disorders, use of medications associated with low bone mass or bone loss such as corticosteroids); or
    2. Inadequate response or inability to tolerate ONE of the following osteoporosis therapies:
      1. Bisphosphonates; or
      2. Hormone replacement therapy; or
      3. Selective-estrogen receptor modulators (SERMs); or
      4. Calcitonin-salmon (Miacalcin®); or
      5. Denosumab (Prolia®); and
  4. For Forteo® only, inadequate response or inability to tolerate Teriparatide® manufactured by Alvogen

Initial Authorization duration: 12 months  

REAUTHORIZATION CRITERIA: Abaloparatide (Tymlos™) or teriparatide (Forteo®) is medically necessary when BOTH of the following are met:

  1. Documentation of positive clinical response; and
  2. ONE of the following:
    1. Cumulative lifetime therapy does not exceed 2 years; or
    2. For Forteo® only, member remains at or has returned to having a high risk for fracture despite a total of 24 months of use for parathyroid hormones 

Reauthorization duration: 12 months

Increase bone density in men with osteoporosis at high risk for fracture

INITIAL CRITERIA: Abaloparatide (Tymlos®) is medically necessary when ALL of the following are met:

  1. Diagnosis of primary or hypogonadal osteoporosis; and
  2. The member is 18 years of age or older; and
  3. Both of the following:
    1. Bone mineral density (BMD) T-score of -2.5 or lower in the lumbar spine, femoral neck, total hip, or radius (one-third radius site); and
    2. One of the following:
      1. History of low-trauma fracture of the hip, spine, proximal humerus, pelvis, or distal forearm; or
      2. Inadequate response or inability to tolerate at least one osteoporosis treatment (e.g., alendronate, zoledronic acid, Prolia [denosumab])

Initial authorization duration: 12 months

REAUTHORIZATION CRITERIA: Abaloparatide (Tymlos®) is medically necessary when BOTH of the following are met:
  1. Documentation of positive clinical response; and
  2. Cumulative lifetime therapy does not exceed 2 years

Reauthorization duration: 12 months

* Coverage duration of Teriparatide and Tymlos™ is limited to 730-day supply max per lifetime. All other treatment durations are considered Experimental/Investigational.

**Osteoporosis defined as T score of the individual's bone mineral density (BMD) is at least -2.5 standard deviations below the young adult mean OR history of osteoporotic fracture (i.e. hip, spine, etc.)

N/A

Forteo® (teriparatide) [package insert]. Indianapolis, IN. Lilly USA, LLC. April 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=aae667c5-381f-4f92-93df-2ed6158d07b0&type=display. Accessed October 14, 2024.

Prolia® (denosumab) [package insert]. Thousand Oaks, CA. Amgen Inc. January 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=49e5afe9-a0c7-40c4-af9f-f287a80c5c88&type=display. Accessed October 14, 2024.

Rosen CJ. Parathyroid hormone/parathyroid hormone-related protein analog for osteoporosis. UpToDate. January 2023. Available at: https://www.uptodate.com/contents/parathyroid-hormone-therapy-for-osteoporosis?source=search_result&search=teriparatide&selectedTitle=4~150. Accessed October 14, 2024.

Tymlos™ (abaloparatide) [package insert]. Waltham, MA: Radius Health, Inc. December 2022. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=712143d9-e21e-4013-bb3b-3426a21060a8&type=display. Accessed October 14, 2024.


189/12/20249/11/20251/1/2025 1:11 AMNo presence informationsrv_ppsgw_P
Rx.01.33 Off-Label Use

​Brand Name​​Generic Name
​Tymlos™
​abaloparatide
​Forteo®​teriparatide

Tymlos™, Forteo®abaloparatide, teriparatide
486
  
1/1/2025Rx.01.148CommercialVanHorn, LynnseyQ3-2024

Actinic keratoses (AKs or solar keratoses) are keratotic macules, papules, or plaques resulting from the intraepidermal proliferation of atypical keratinocytes in response to prolonged exposure to ultraviolet radiation. AKs are a concern because the majority of cutaneous squamous cell carcinoma (SCCs) arise from pre-existing AKs, and AKs that will progress to SCC cannot be distinguished from AKs that will spontaneously resolve or persist.

Cutaneous T cell lymphoma (CTCL) describes a heterogeneous group of neoplasms of skin-homing T cells. CTCL represent approximately 75 to 80 percent of all primary cutaneous lymphomas. Mycosis fungoides (MF) and primary cutaneous CD30+ lymphoproliferative disorders (LPD) account for approximately 90 percent of CTCL.

Ingenol mebutate (Picato®) is indicated for the topical treatment of actinic keratosis (AK).

Ingenol mebutate (Picato®) is an inducer of cell death. The mechanism of action by which ingenol mebutate gel induces cell death in treating AK lesions is unknown.

Diclofenac 3% gel (Solaraze®) is indicated for the topical treatment of AK.

The mechanism of action of diclofenac 3% gel (Solaraze®) in the treatment of AK is unknown.

Tirbanibulin (Klisyri™) is indicated for the topical treatment of actinic keratosis on the face or scalp.

Tirbanibulin is a microtubule inhibitor. The mechanism of action of KLISYRI for the topical treatment of actinic keratosis is unknown. 

 

Imiquimod (Zyclara™) is indicated for the topical treatment of clinically typical visible or palpable, actinic keratoses (AK) of the full face or baling scalp in immunocompetent adults and the treatment of external genital and perianal warts (EGW)/condyloma acuminata in patients 12 years or older.


Imiquimod is a Toll-like receptor 7 agonist. The mechanism of action of Zyclara™ in treating AK and EGW lesions is unknown.


The intent of this policy is to communicate the medical necessity criteria for  ingenol mebutate (Picato®) diclofenac 3% (Solaraze®) tirbanibulin (Klisyri®), and imiquimod (Zyclara™) as provided under the member's prescription drug benefit.

Actinic Keratosis
 
INITIAL CRITERIA Ingenol mebutate (Picato®), diclofenac 3% (Solaraze®) gel, imiquimod (Zyclara®) 3.75%, 2.5%, or tirbanibulin (Klisyri®) is medically necessary when BOTH of the following are met:

  1. Diagnosis of actinic keratosis; and
  2. Member is 18 years of age or older; and 
  3. ONE of the following:
    1. For imiquimod (Zyclara®) 3.75%, 2.5% only, inadequate response or inability to tolerate imiquimod 5%; or
    2. For tirbanibulin (Klisyri®) only, inadequate response or inability to tolerate BOTH of the following generics:
      1. Fluorouracil; and
      2. Imiquimod

Initial authorization duration:
  • 30 days for tirbanibulin (Klisyri®), ingenol mebutate (Picato®) imiquimod (Zyclara®) 3.75%, 2.5%.
  • 3 months for diclofenac 3% (Solaraze®)


REAUTHORIZATION CRITERIA Ingenol mebutate (Picato®), diclofenac 3% (Solaraze®) gel, imiquimod (Zyclara®) 3.75%, 2.5%, or tirbanibulin (Klisyri®) is medically necessary when there is documentation of a diagnosis of actinic keratosis at a different site.

Reauthorization duration:

  • 30 days for tirbanibulin (Klisyri®), ingenol mebutate (Picato®) imiquimod (Zyclara®) 3.75%, 2.5%.
  • 3 months for diclofenac 3% (Solaraze®) 

Genital warts

INITIAL CRITERIA Imiquimod (Zyclara®) 3.75% is medically necessary when BOTH of the following are met:

  1. Diagnosis of genital warts; and
  2. Member is 12 years of age or older; and
  3. Inadequate response or inability to tolerate imiquimod 5%

Initial authorization duration: 30 days
 
REAUTHORIZATION CRITERIA Imiquimod (Zyclara®) 3.75% is medically necessary when there is documentation of positive clinical response to therapy.

 Reauthorization duration: 30 days


Solaraze® (diclofenac 3%):

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial and stroke, which can be fatal. This risk may occur in treatment and may increase with duration of use.

Solaraze® is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Berman B. Treatment of actinic keratosis. UpToDate. July 2024. Available at: https://www.uptodate.com/contents/treatment-of-actinic-keratosis?source=search_result&search=actinic%20keratosis&selectedTitle=1~46. Accessed October 09, 2024.

Picato® (ingenol mebutate) [package insert]. Parsippany, NJ.  Leo Pharma Inc. March 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5accc7a5-8209-4680-b0ae-2a6963500419&type=display.  Accessed October 09, 2024.

Solaraze® (diclofenac 3%) [package insert]. Melville, NY. PharmaDerm. April 2016. Available at:  https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=89a7bfbd-051f-4d87-a642-96b0df81b8e2&type=display. Accessed October 09, 2024.

Willemze R. Classification of primary cutaneous lymphomas. UpToDate. August 2024. Available at: https://www.uptodate.com/contents/classification-of-primary-cutaneous-lymphomas?source=machineLearning&search=CTCL&selectedTitle=7~106&sectionRank=1&anchor=H474649238#H474649238. Accessed October 09, 2024.

Klisyri™ (tirbanibulin) [package insert]. Exton, PA: Almirall; June 2024. Available from: https://klisyrihcp.com/assets/klisyri-prescribing-information.pdf. Accessed October 09, 2024.

Zyclara™ (imiquimod) [package insert]. Bridgewater, NJ: Bausch Health US, LLC; October 2024. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=28cd9b5b-680b-480f-b33d-9c5b52bbf03d. Accessed October 09, 2024.​

149/12/20249/12/20251/1/2025 1:12 AMNo presence informationsrv_ppsgw_P
Off-Label Use policy Rx.01.33
Brand NameGeneric Name
Picato®ingenol mebutate

Solaraze®

Klisyri™

diclofenac 3%

Tirbanibulin

Zyclara™Imiquimod

Picato®, Solaraze®,Klisyri®, and Zyclara™ingenol mebutate, diclofenac 3%, tirbanibulin, and imiquimod
526
  
1/1/2025Rx.01.226CommercialVanHorn, LynnseyQ3-2024

Seizures can result from a shift in the normal balance of excitation and inhibition within the CNS as well as abnormal brain function. Epilepsy is a chronic medical disorder when two or more unprovoked seizures occur that can't be explained by a medical condition. Abnormal, excessive, and hypersynchronous electrical discharge of neurons in the brain can manifest epileptic seizures. Seizure clusters, also known as acute repetitive seizures are frequent seizure activities that are distinct from a patient's usual seizure pattern. Benzodiazepines are used as a rescue medication for seizure clusters in an outpatient setting.

Midazolam (Nayzilam®) nasal spray is a benzodiazepine indicated for the acute treatment of intermittent, stereotypic  episodes of  frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern in patients with epilepsy 12 years of age and older.

Diazepam (Valtoco®) nasal spray is a  benzodiazepine indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern in patients with epilepsy 6 years of age and older.

Diazepam (Libervant™) buccal film is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy 2 to 5 years of age.

The exact mechanism of action for Nayzilam® and Valtoco® is not fully understood, but it is thought to involve potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site of the GABAA receptor.



The intent of this policy is to communicate the medical necessity criteria for midazolam (Nayzilam®) nasal spray, diazepam (Valtoco®) nasal spray, and diazepam (Libervant™) buccal film as provided under the member's prescription drug benefit.

​INITIAL CRITERIA: Midazolam (Nayzilam®), Diazepam (Libervant™) buccal film or Diazepam (Valtoco®) nasal spray is approved when ALL of the following are met:

  1. Diagnosis of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern; and
  2. ONE of the following:
    1. For midazolam (Nayzilam®) only, member is 12 years of age or older; or
    2. For diazepam (Libervant™) only, member is 2 to 5 years of age; or
    3. For diazepam (Valtoco®) only, member is 6 years of age or older; and
  3. Prescribed by or in consultation with a neurologist/epilepsy specialist

Initial Authorization duration: 2 years

REAUTHORIZATION CRITERIA: Midazolam (Nayzilam®) nasal spray, Diazepam (Libervant™) buccal film or diazepam (Valtoco®) nasal spray is reapproved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years


Benzodiazepines (Nayzilam®, Valtoco®, Libervant):

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. 

The unapproved use benzodiazepines (Nazyilam, Valtoco, Libervant) exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Assess each patient’s risk for abuse, misuse, and addiction.

Although benzodiazepine (Nayzilam, Valtoco, Libervant) is indicated only for intermittent use, if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction of benzodiazepine (Nayzilam, Valtoco, Libervant) may precipitate acute withdrawal reactions, which can be life-threatening. For patients using benzodiazepine (Nayzilam, Valtoco, Libervant) more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue benzodiazepine (Nayzilam, Valtoco, Libervant).


Libervant™ (diazepam buccal film) [prescribing information]. Warren, NJ: Aquestive Therapeutics, Inc.; April 2024. Available from libervant-2-to-5-years-of-age-pi-clean-pdf.pdf (aquestive.com). Accessed October 11, 2024.

Nayzilam® (midazolam nasal spray) [prescribing information]. Smyrna, GA: UCB Inc.; January 2023. Available from: https://www.ucb-usa.com/_up/ucb_usa_com_kopie/documents/Nayzilam_PI.pdf. Accessed October 11, 2024. 

Valtoco® (diazepam nasal spray) [prescribing information]. San Diego, CA: Neurelis, Inc.; January 2023. Available from: https://www.valtoco.com/sites/default/files/Prescribing_Information.pdf. Accessed October 11, 2024.

Jafarpour, Saba & Hirsch, Lawrence & Gaínza-Lein, Marina & Kellinghaus, Christoph & Detyniecki, Kamil. (2018). Seizure cluster: Definition, prevalence, consequences, and management. Seizure. 68. 10.1016/j.seizure.2018.05.013. October 11, 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
Nayzilam®Midazolam
Valtoco®Diazepam
Libervant™Diazepam


LIBERVANT    MISDIAZEPAM BUCCAL FILM 10 MG, 12.5 MG, 15 MG, 5 MG, 7.5 MG
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.



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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
Inbrija™Levodopa inhalation
Nourianz™Istradefylline
Apokyn®Apomorphine
Kynmobi™Apomorphine


NANA
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. 


143/14/20243/14/20257/1/2024 1:22 AMNo presence informationsrv_ppsgw_P
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
487
  
1/1/2025Rx.01.267CommercialVanHorn, LynnseyQ3-2024
Testing for genetic mutations in the PIK3CA gene is done at initial MBC diagnosis if tumor is HR+/HER2- following progression on or after an endocrine-based regimen. This gene effects cell growth and development and can contribute to a worse prognosis for patients. Knowledge of the presence of this mutation can inform providers in their treatment selection for these patients.

Alpelisib is a small-molecule phosphatidylinositol-3-kinase (PI3K) inhibitor with selective (and strong) activity against PI3Kα (André 2019). Mutations in the gene encoding the catalytic α-subunit of PI3K (PI3KCA) lead to activation of PI3Kα and Akt-signaling, cellular transformation, and tumor generation. Alpelisib inhibits phosphorylation of PI3K downstream targets (including Akt) and demonstrated activity in cell lines harboring a PIK3CA mutation. When compared with either agent alone, the combination of alpelisib with fulvestrant has synergistic antitumor activity in PIK3CA-mutated, estrogen receptor-positive models.

Activating mutations in PIK3CA may induce a spectrum of overgrowths/malformations comprising clinically recognizable disorders commonly known as PIK3CA-related overgrowth spectrum (PROS). In an animal model PROS phenotype (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal syndrome [CLOVES]), alpelisib inhibited the PI3K pathway, resulting in prevention or improvement of organ abnormalities associated with the disease; findings were reversed following alpelisib withdrawal

Breast cancer, advanced or metastatic: Treatment (in combination with fulvestrant) of HR-positive, HER2-negative, PIK3CA-mutated (as detected by an approved test), advanced or metastatic breast cancer in males and postmenopausal females following progression on or after an endocrine-based regimen.

PIK3CA-related overgrowth spectrum: Treatment of severe manifestations of PIK3CA-related overgrowth spectrum in patients ≥2 years of age who require systemic therapy.

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

INITIAL CRITERIA Alpelisib (Vijoice) is medically necessary when ALL of the following are met:

  1. Diagnosis of PIK3CA-Related Overgrowth Spectrum (PROS); and
  2. Documentation of mutation in the PIK3CA gene; and
  3. Member is 2 years of age or older; and
  4. Documentation of severe clinical manifestations (e.g., Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, Scoliosis/skeletal and spinal [CLOVES], Facial Infiltrating Lipomatosis [FIL], Klippel-Trenaunay Syndrome [KTS], Megalencephaly-Capillary Malformation Polymicrogyria [MCAP]); and
  5. Prescribed by or in consultation with a provider who specialized in the treatment of PROS 


Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA Alpelisib (Vijoice®) is medically necessary when ALL of the following are met:

  1. Documentation of positive clinical response to therapy (e.g., radiological response defined as a ≥ 20% reduction from baseline in the sum of target lesion volume); and
  2. Prescribed by or in consultation with a provider who specializes in the treatment of PROS

Reauthorization duration: 12 months 


N/A

André F, Ciruelos E, Rubovszky G, et al; SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019;380(20):1929-1940.[PubMed 31091374]

Venot Q, Blanc T, Rabia SH, et al. Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature. 2018;558(7711):540-546. doi:10.1038/s41586-018-0217-9[PubMed 29899452]

Vijoice® (alpelisib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; April 2024. Available from: https://www.novartis.com/us-en/sites/novartis_us/files/vijoice.pdf. Accessed October 09, 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
Vijoice®Alpelisib

Vijoice®Alpelisib
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
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
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
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.
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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
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
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
488
  
1/1/2025Rx.01.256CommercialVanHorn, LynnseyQ3-2024

Graft-versus-host disease (GVHD) can develop after allogeneic hematopoietic cell transplant (HCT), when immune cells from a non-identical donor (the graft) initiate an immune reaction against a transplant recipient (the host). Chronic GVHD is a syndrome of variable clinical features that resembles autoimmune and other immunologic disorders (eg, scleroderma, Sjögren's syndrome, primary biliary cirrhosis, bronchiolitis obliterans). Clinical manifestations may be widespread, or they may be restricted to a single organ or site. The primary clinical manifestations are skin involvement (resembling lichen planus or cutaneous scleroderma), dry oral mucosa, gastrointestinal tract ulcerations and sclerosis, elevated serum bilirubin, and bronchiolitis obliterans. Chronic GVHD is a major cause of morbidity and mortality after allogeneic HCT, which worsen with increasing disease severity. Patients have impaired physical, social, and psychological well-being and impaired quality of life.

Belumosudil is an inhibitor of rho-associated, coiled-coil containing protein kinase (ROCK) which inhibits ROCK2 and ROCK1 with IC50 values of approximately 100 nM and 3 μM, respectively. Belumosudil down- regulated proinflammatory responses via regulation of STAT3/STAT5 phosphorylation and shifting Th17/Treg balance in ex-vivo or in vitro-human T cell assays. Belumosudil also inhibited aberrant pro-fibrotic signaling, in vitro. In vivo, belumosudil demonstrated activity in animal models of chronic GVHD.

REZUROCK is a kinase inhibitor indicated for the treatment of adult and pediatric patients 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic therapy.

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

INITIAL CRITERIA Belumosudil (Rezurock™) is medically necessary when ALL of the following are met:

  1. Diagnosis of chronic graft-versus-host disease; and
  2. Member is 12 years of age or older; and
  3. Inadequate response or inability to tolerate two or more lines of systemic therapy (e.g., corticosteroids, mycophenolate, etc.); and
  4. Prescribed by or in consultation with one of the following:
    1. Hematologist; or
    2. Oncologist; or
    3. Physician experienced in the management of transplant patients

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA Belumosudil (Rezurock™) is medically necessary if member does not show evidence of progressive disease while on therapy

Reauthorization duration: 2 years


N/A

Rezurock™ [package insert]. Warrendale, PA: Kadmon Pharmaceuticals. April 2024. Available at: https://www.rezurock.com/full-prescribing-information.pdf. Accessed October 09, 2024.

Zeiser R. Clinical manifestations and diagnosis of chronic graft-versus-host disease. UpToDate website. Last updated February 2024. Available at http://www.uptodate.com/. Accessed October 09, 2024.

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​Rx.01.33 Off Label Use
Brand NameGeneric Name
RezurockTMBelumosudil

Rezurock™Belumosudil
478
  
10/1/2024Rx.01.294CommercialOyenusi, OluwadamilolaQ2-2024
Epidermolysis bullosa (EB) is a group of hereditary rare diseases that cause the skin to be fragile and to blister easily. There are four major types of EB, based upon the ultrastructural level of tissue cleavage in the skin: epidermolysis bullosa simplex (EBS), junctional epidermolysis bullosa (JEB), dystrophic epidermolysis bullosa (DEB), and Kindler epidermolysis bullosa (KEB). There is no cure for EB. The management of patients with EB is largely supportive and includes wound care and prevention and treatment of complications.

The mechanism of action of FILSUVEZ in the treatment of wounds associated with epidermolysis bullosa is unknown.

Filsuvez® is indicated for the treatment of wounds associated with dystrophic and junctional epidermolysis bullosa (EB) in adult and pediatric patients 6 months of age and older.

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

INITIAL CRITERIA: Birch triterpenes (Filsuvez®) is approved when ALL of the following are met:

  1. Diagnosis of one of the following:
    1. Dystrophic epidermolysis bullosa (DEB); or
    2. Junctional epidermolysis bullosa (JEB); and
  2. Disease is confirmed by one of the following:
    1. Genetic testing confirms mutation in one of the following genes:
      1. For Dystrophic epidermolysis bullosa (DEB), collagen type VII (COL7A1); or
      2. For Junctional epidermolysis bullosa (JEB), one of the following:
        1. ITGA6; or
        2. ITGB4; or
        3. Collagen type XVII (COL17A1); or
        4. LAMA3; or
        5. LAMB3; or
        6. LAMC2; or
        7. ITGA3; or
        8. LAMA3A; or
    2. Skin biopsy; and
  3. Member is 6 months of age or older; and
  4. Medication will be used for the treatment of wounds; and
  5. DEB or JEB associated wounds are present for at least 21 days and less than 9 months; and
  6. Member does not have signs of infection for wound being treated; and
  7. Member has no evidence or history of basal or squamous cell carcinoma for wound being treated; and
  8. Member does not have history of stem cell transplant or gene therapy (e.g., Vyjuvek) for the treatment of epidermolysis bullosa; and
  9. Standard wound care management not adequate in healing wounds (e.g., daily wound dressings, pain management, controlling infections); and
  10. Prescribed by or in consultation with a dermatologist with expertise in the treatment of epidermolysis bullosa

 

Initial authorization duration: 3 months

 

REAUTHORIZATION CRITERIA: Birch triterpenes (Filsuvez®) is re-approved when ALL of the following are met:

  1. Member demonstrates positive clinical response to therapy as evidenced by wound is healing but not completely closed; and
  2. Member does not have signs of infection for wound being treated; and
  3. Member has no evidence or history of basal or squamous cell carcinoma for wound being treated; and
  4. Prescribed by or in consultation with a dermatologist with expertise in the treatment of epidermolysis bullosa

 

Reauthorization duration: 6 months


N/A
National Institute of Arthritis and Musculoskeletal and Skin Diseases. Epidermolysis Bullosa. U.S. Department of Health and Human Services, National Institutes of Health. September 2023. Available at: https://www.niams.nih.gov/health-topics/epidermolysis-bullosa. Accessed July 31, 2024.

Murrell DF. Overview of the management of epidermolysis bullosa. In: UpToDate, Connor RF (Ed), Wolters Kluwer. Accessed July 31, 2024.

Filsuvez® (Birch triterpenes) [package insert]. Wahlstedt, Germany: Lichtenheldt GmbH Pharmazeutische Fabrik. May 2024. Available at: 
https://resources.chiesiusa.com/Filsuvez/FILSUVEZ_PI.pdf. Accessed July 31, 2024.


17/1/20246/6/202510/1/2024 1:19 AMNo presence informationsrv_ppsgw_P
Off-Label Use Rx.01.33

Quantity level limits for pharmaceuticals covered under the prescription drug benefit Rx.01.76

​Brand Name​Generic Name
​Filsuvez®​Birch triterpenes

Filsuvez® birch triterpenes
519
  
1/1/2025Rx.01.208CommercialVanHorn, LynnseyQ3-2024

Idiopathic thrombocytopenia purpura (ITP): ITP is an immune disorder in which the blood doesn't clot normally. ITP can cause excessive bruising and bleeding and can be characterized as an unusually low level of platelets, or thrombocytes, in the blood results in ITP.

Thrombocytopenia in patients with hepatitis C: Thrombocytopenia can occur in patients with chronic hepatitis C virus (HCV) infection. The pathophysiology is multifactorial and includes direct bone marrow suppression, an overactive spleen, decreased production of thrombopoietin and therapeutic adverse effect all contributing to thrombocytopenia.

Aplastic Anemia: A blood disorder caused by failure of the bone marrow to make enough new blood cells. Bone marrow is a sponge-like tissue inside the bones that makes stem cells that differentiate into red blood cells, white blood cells, and platelets.

Thrombocytopenia in patients with chronic liver disease: Individuals with chronic liver disease have varying degree of thrombocytopenia which may be caused by impaired platelet production from decreased hepatic synthesis of thrombopoietin. In addition, individuals with advanced liver disease may have reduced platelet function due to coexisting uremia, infection, and/or endothelial abnormalities. These factors combined put the individuals with chronic liver disease at an increased risk for bleeding especially during procedures.

Mechanism of Action:

Eltrombopag olamine (Promacta®) tablets contain a thrombopoietin (TPO) receptor agonist for oral administration. Eltrombopag interacts with the transmembrane domain of the TPO receptor which initiates signaling cascades that induce proliferation and differentiation from bone marrow progenitor cells ultimately increasing platelet production. 

Eltrombopag olamine (Promacta®) is a thrombopoietin receptor agonist indicated for the treatment of:

  1. Thrombocytopenia in adult and pediatric patients 1 year and older with chronic idiopathic thrombocytopenia purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. PROMACTA should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. 
  2. Thrombocytopenia in patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy. PROMACTA should only be used in patients with chronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon-based therapy or limits the ability to maintain interferon-based therapy. 
  3. In combination with standard immunosuppressive therapy for the first-line treatment of adult and pediatric patients 2 years and older with severe aplastic anemia.
  4. Patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.

Fostamatinib disodium (Tavalisse™) is a tyrosine kinase inhibitor with demonstrated activity against spleen tyrosine kinase (SYK). The major metabolite of fostamatinib, R406, inhibits signal transduction of Fc-activating receptors and B-cell receptor. The fostamatinib metabolite R406 reduces antibody-mediated destruction of platelets.

Fostamatinib disodium (Tavalisse™) is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Avatrombopag (Doptelet®) and lusutrombopag (Mupleta®) tablets contain a thrombopoietin (TPO) receptor agonist for oral administration. They stimulate proliferation and differentiation of megakaryocytes from bone marrow progenitor cells resulting in an increased production of platelets. Avatrombopag does not compete with TPO for binding to the TPO receptor and has an additive effect with TPO on platelet production. Lusutrombopag induces megakaryocyte maturation by interacting with the transmembrane domain of human TPO receptor expressed on megakaryocytes.

Avatrombopag (Doptelet®) and Lusutrombopag (Mupleta®)are indicated for the treatment of thrombocytopenia in adult patients  with chronic liver disease who are scheduled to undergo a procedure. ​​

Doptelet® (avatrombopag) is also indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment.

Alvaiz™ (eltrombopag choline) is a thrombopoietin receptor agonist indicated:
  • for the treatment of thrombocytopenia in adult and pediatric patients 6 years and older with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. ALVAIZ should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. 
  • for the treatment of thrombocytopenia in adult patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy. ALVAIZ should be used only in patients with chronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon-based therapy or
  • limits the ability to maintain interferon-based therapy. 
  • for the treatment of adult patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy. 

The intent of this policy is to communicate the medical necessity criteria for eltrombopag choline (Alvaiz™), eltrombopag olamine (Promacta®), fostamatinib disodium (Tavalisse™), avatrombopag (Doptelet®), lusutrombopag (Mulpleta®) as provided under the member's prescription drug benefit.

Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP)

INITIAL CRITERIA: Eltrombopag olamine (Promacta®) or eltrombopag choline (Alvaiz™) is approved when ALL of the following are met:

  1. Diagnosis of relapsed/refractory chronic immune (idiopathic) thrombocytopenic purpura (ITP) for greater than 6 months; and
  2. ONE of the following:
    1. For eltrombopag olamine (Promacta®) only, member is 1 year of age or older; or
    2. For eltrombopag choline (Alvaiz™) only, member is 6 years of age or older; and
  3. Baseline platelet count is less than 30,000/mcL; and
  4. Insufficient response to corticosteroids, immunoglobulins, or splenectomy; and
  5. Prescribed by or in consultation with a hematologist/oncologist ; and
  6. Member's degree of thrombocytopenia and clinical condition increase the risk of bleeding

INITIAL CRITERIA: Fostamatinib (Tavalisse™) is approved when all of the following are met:

  1. Diagnosis of relapsed/refractory chronic immune (idiopathic) thrombocytopenic purpura (ITP); and
  2. Baseline platelet count is less than 30,000/mcL; and
  3. Member's degree of thrombocytopenia and clinical condition increase the risk of bleeding; and
  4. Documentation of an inadequate response or inability to tolerate ONE of the following:
    1. Corticosteroids; or 
    2. Immunoglobulins; or
    3. Splenectomy; or
    4. Thrombopoietin receptor agonists (e.g., Nplate®, Promacta®); or
    5. Rituximab; and
  5. Prescribed by or in consultation with a hematologist/oncologist; and
  6. Member is 18 years of age or older

Initial authorization duration: 2 years
 
INITIAL CRITERIA: Avatrombopag (Doptelet®) is approved when ALL of the following are met:

  1. Diagnosis of relapsed/refractory chronic immune thrombocytopenia purpura (ITP); and
  2. Baseline platelet count is less than 30,000mcL; and
  3. Inadequate response or inability to tolerate ONE of the following: 
    1. corticosteroids; or
    2. immunoglobulins; or
    3. splenectomy; or
    4. Rituxan (rituximab); and
  4. Member's degree of thrombocytopenia and clinical condition increase the risk of bleeding; and
  5.  Prescribed by or in consultation with a hematologist/oncologist; and
  6. Member is 18 years of age or older

Initial authorization duration: 2 years

CONTINUATION CRITERIA: Eltrombopag olamine (Promacta®), eltrombopag choline (Alvaiz™), Fostamatinib (Tavalisse™), avatrombopag (Doptelet®) is re-approved when ALL of the following are met:

  1. Diagnosis of chronic immune (idiopathic) thrombocytopenic purpura; and
  2. Documentation of a positive clinical response to Promacta®, Alvaiz™, Tavalisse™, Doptelet® therapy as evidence by an increase in platelet count to a level sufficient to avoid clinically important bleeding; and
  3. Prescribed by or in consultation with a hematologist/oncologist


Continuation authorization duration: 2 years.

Aplastic anemia
 
INITIAL CRITERIA: Eltrombopag olamine (Promacta®) is approved when ALL of the following are met:

  1. Diagnosis of severe aplastic anemia; and
  2. Member is 2 years of age or older; and
  3. One of the following:
    1. Inadequate response or inability to tolerate immunosuppressive therapy with antithymocyte globulin (ATG) and cyclosporine; or
    2. Documentation that the requested drug will be used in combination with antithymocyte globulin (ATG) and cyclosporin and
  4. Member has thrombocytopenia defined as platelet count less than 30,000/mcL; and
  5. Prescribed by or in consultation with a hematologist/oncologist

Initial authorization duration: 2 years

INITIAL CRITERIA: Eltrombopag choline (Alvaiz™) is approved when ALL of the following are met:

  1. Diagnosis of refractory severe aplastic anemia; and
  2. Member is 18 years of age or older; and
  3. Inadequate response or inability to tolerate immunosuppressive therapy with antithymocyte globulin (ATG) and cyclosporine; and
  4. Member has thrombocytopenia defined as platelet count less than 30,000/mcL; and
  5. Prescribed by or in consultation with a hematologist/oncologist

Initial authorization duration: 16 weeks
 

CONTINUATION CRITERIA: Eltrombopag olamine (Promacta®) or eltrombopag choline (Alvaiz™) is re-approved when ALL of the following are met:

  1. Diagnosis of severe aplastic anemia; and
  2. Documentation of a positive clinical response to therapy as evidenced by an increase in platelet count; and
  3. Prescribed by or in consultation with a hematologist/oncologist

Continuation authorization duration: 2 years

Thrombocytopenia associated with hepatitis C
 
INITIAL CRITERIA: Eltrombopag olamine (Promacta®) or eltrombopag choline (Alvaiz™) is approved when ALL of the following are met:

  1. Diagnosis of thrombocytopenia associated with hepatitis C; and
  2. Member is 18 years of age or older; and
  3. ONE of the following:
    1. Member has thrombocytopenia defined as platelets less than 90,000/mcL for initiation (pre-treatment) of interferon-based therapy; or
    2. Member has thrombocytopenia defined as platelets less than 75,000/mcL for maintenance of optimal interferon-based therapy; and
  4. Prescribed by or in consultation with one of the following:
    1. Hematologist/ oncologist
    2. Gastroenterologist
    3. Hepatologist
    4. Infectious disease specialist
    5. HIV specialist

Initial authorization duration: 48 weeks


CONTINUATION CRITERIA: Eltrombopag olamine (Promacta®) or eltrombopag (Alvaiz®) is re-approved when ALL of the following are met:

  1. Diagnosis of thrombocytopenia associated with hepatitis C; and
  2. ONE of the following:
    1. For members that started treatment with eltrombopag olamine (Promacta®) or eltrombopag choline (Alvaiz™) prior to initiation of treatment with interferon, BOTH of the following:
      1. Member is currently on antiviral interferon therapy for treatment of chronic hepatitis C, and
      2. Member reached a threshold platelet count that allows initiation of antiviral interferon therapy with eltrombopag olamine (Promacta®) or eltrombopag choline (Alvaiz™) treatment by week 9; or
    2. For members that started treatment with eltrombopag olamine (Promacta®) or eltrombopag choline (Alvaiz™) while on concomitant treatment with interferon, member is currently on antiviral interferon therapy for treatment of chronic hepatitis C; and
  3. Prescribed by or in consultation with one of the following:
    1. Hematologist/ oncologist
    2. Gastroenterologist
    3. Hepatologist
    4. Infectious disease specialist
    5. HIV specialist

Continuation authorization duration: 48 weeks

Thrombocytopenia in Chronic Liver Disease Prior to Planned Procedure

Lusutrombopag (Mulpleta®) or Avatrombopag (Doptelet®) is approved when ALL of the following are met:

  1. Diagnosis of thrombocytopenia; and
  2. Member has chronic liver disease; and
  3. Member is scheduled to undergo a procedure; and
  4. Baseline platelet count is less than 50,000/mcL; and
  5. Member is 18 years of age or older; and

  6. For Lusutrombopag (Mulpleta®) only, inadequate response or inability to tolerate avatrombopag (Doptelet®)

Approval duration: 1 month

Promacta® (eltrombopag olamine):
WARNING: RISK FOR HEPATIC DECOMPENSATION IN PATIENTS WITH CHRONIC HEPATITIS C and RISK OF HEPATOTOXICITY
In patients with chronic hepatitis C, PROMACTA in combination with interferon and ribavirin may increase the risk of hepatic decompensation. PROMACTA may increase the risk of severe and potentially lifethreatening hepatotoxicity. Monitor hepatic function and discontinue 
dosing as recommended. 

Alvaiz™ (eltrombopag choline): 
WARNING: RISK FOR HEPATIC DECOMPENSATION IN PATIENTS WITH CHRONIC HEPATITIS C and RISK OF HEPATOTOXICITY
In patients with chronic hepatitis C, ALVAIZ in combination with interferon and ribavirin may increase the risk of hepatic decompensation. ALVAIZ may increase the risk of severe and potentially life-threatening hepatotoxicity. Monitor hepatic function and discontinue dosing as recommended. 

“Aplastic Anemia." Genetic and Rare Diseases Information Center, National Institute of Health, 5 July 2017, rarediseases.info.nih.gov/diseases/5836/aplastic-anemia. Accessed October 10, 2024.

Dahal, Sumit, et al. “Thrombocytopenia in Patients with Chronic Hepatitis C Virus Infection." Advances in Pediatrics., U.S. National Library of Medicine, 1 Mar. 2017, www.ncbi.nlm.nih.gov/pmc/articles/PMC5333732/. Accessed October 10, 2024.

Doptelet® (avatrombopag) [package insert]. Durham, NC. AkaRx, Inc. July 2021. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=e2d5960d-6c18-46cc-86bd-089222b09852&type=display. Accessed October 10, 2024.

Eltrombopag olamine (Promacta®) [package insert]. Basel, Switzerland. Novartis Pharmaceuticals Co. Ltd. March 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=7714a0ed-34bb-46e6-a0a5-b363908b22c2&type=display. Accessed October 10, 2024.

Mulpleta® (lusutrombopag) [package insert]. Florham Park, NJ. Shionogi Inc., April 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f9fd0cfd-717d-4a87-99bc-de7b38807e55&type=display. Accessed October 10, 2024.

Shah, N. MD, Intagliata, N, MD. March 2024. Hemostatic abnormalities in patients with liver disease. UpToDate. Access October 10, 2024.

“Idiopathic Thrombocytopenic Purpura (ITP)." Mayo Clinic, Mayo Foundation for Medical Education and Research, June 2023, www.mayoclinic.org/diseases-conditions/idiopathic-thrombocytopenic-purpura/diagnosis-treatment/drc-20352330. Accessed October 10, 2024.

Tavalisse™ (fostamatinib) [package insert]. San Francisco, CA. Rigel Pharmaceutical, Inc. November 2020. Available from: https://tavalisse.com/downloads/pdf/Tavalisse-Full-Prescribing-Information.pdf. Accessed October 10, 2024.

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Rx.01.33 Off Label Use

​Brand Name​Generic Name
​Promacta®​Eltrombopag olamine
​Tavalisse™​fostamatinib
​Doptelet®​avatrombopag
​Mulpleta®​lusutrombopag
​Alvaiz™​eltrombopag choline

N/AN/A
477
  
10/1/2024Rx.01.293CommercialOyenusi, OluwadamilolaQ2-2024
Eosinophilic esophagitis (EoE) is a chronic allergic/immune condition of the esophagus. In EoE, large number of eosinophils are found in the inner lining of the esophagus resulting in inflammation which causes symptoms such as chest pain ,heartburn, difficulty swallowing, or impaction. roton pump inhibitors (PPIs) are among first line treatment options, together with dietary modification and topical glucocorticoids. Clinical manisfestations in adults include: dysphagia, food impaction, chest pain that is often centrally located and may not respond to antacids, gastroesophageal reflux disease-like symptoms/refractory heartburn, and upper abdominal pain.

Budesonide is an anti-inflammatory corticosteroid and has a high glucocorticoid effect and a weak mineralocorticoid effect, and the affinity of budesonide to glucocorticoid receptors, which reflects the intrinsic potency of the drug, is about 200-fold that of cortisol and 15-fold that of prednisolone.

The precise mechanism of corticosteroid actions on inflammation in EoE is not known. Inflammation is an important component in the pathogenesis of EoE. Corticosteroids have a wide range of inhibitory activities against multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukocytes and cytokines) involved in allergic inflammation.

Eohilia™ is indicated for 12 weeks of treatment in adult and pediatric patients 11 years of age and older with eosinophilic esophagitis (EoE).

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

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

  1. Diagnosis of eosinophilic esophagitis (EoE); and
  2. Member has symptoms of esophageal dysfunction (e.g., dysphagia, food impaction, heartburn, abdominal pain); and
  3. Member has at least 15 intraepithelial eosinophils per high power field (HPF); and
  4. Other causes of esophageal eosinophilia have been ruled out; and
  5. Member is 11 years of age or older; and
  6. Inadequate response or inability to tolerate a minimum 8-week duration of both of the following:
    1. Proton pump inhibitor (e.g., pantoprazole, omeprazole); and
    2. Topical (esophageal) corticosteroid (e.g., budesonide, fluticasone); and
  7. Prescribed by or in consultation with one of the following:
    1. Allergist/immunologist; or
    2. Gastroenterologist

Authorization duration: 12 weeks


N/A
Bonis PA, Gupta SK. Clinical manifestations and diagnosis of eosinophilic esophagitis (EoE). In: UpToDate, Connor RF (Ed), Wolters Kluwer. Accessed July 31, 2024.

Bonis PA, Gupta SK. Treatment of eosinophilic esophagitis (EoE). In: UpToDate, Connor RF (Ed), Wolters Kluwer. Accessed July 31, 2024.

Eohilia™ (budesonide oral suspension) [package insert]. Lexington, MA: Takeda Pharmaceuticals America, Inc. February 2024. Available at: https://content.takeda.com/?contenttype=PI&product=EOH&language=ENG&country=USA&documentnumber=1. Accessed July 31, 2024.
17/1/20246/6/202510/1/2024 1:19 AMNo presence informationsrv_ppsgw_P
Off-Label Use Rx.01.33

Quantity level limits for pharmaceuticals covered under the prescription drug benefit Rx.01.76



​Brand Name​Generic Name
​Eohilia™​Budesonide oral suspension

Eohilia™ budesonide
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. 


33/14/20243/14/20257/1/2024 1:23 AMNo presence informationsrv_ppsgw_P
​Rx.01.33 Off Label Use​
Brand NameGeneric Name
Tarpeyo™Budesonide

NANA
489
  
1/1/2025Rx.01.10CommercialVanHorn, LynnseyQ3-2024

Hyperammonemia is a urea cycle disorder due to a deficiency of an enzyme in the pathway that can cause life-threatening metabolic decompensations in infancy. Survivors frequently have severe neurologic injury. Frequent vomiting and poor appetite with food refusal and protein aversion are common in patients with UCD. In newborns, central hyperventilation leading to respiratory alkalosis is an early sign of hyperammonemia. Infants become symptomatic after feeding in which initial signs include somnolence, inability to maintain normal body temperature, poor feeding followed by vomiting lethargy and coma.

N-acetylglutamate synthetase (NAGS) deficiency is a rare, autosomal, recessive genetic disorder in which lack of NAGS enzyme leads to hyperammonemia (excess ammonia).  NAGS deficiency is one of several urea cycle disorders.

Carglumic acid (Carbaglu®) is a synthetic structural analogue of N-acetylglutamate (NAG), which is produced from glutamate and acetyl-CoA in a reaction catalyzed by N-acetylglutamate synthase (NAGS), a mitochondrial liver enzyme. NAG acts as an essential allosteric activator of carbamoyl phosphate synthetase 1 (CPS 1) in liver mitochondria. CPS 1  catalyzes the first reaction  of the urea cycle, . NAG is the product of NAGS, a mitochondrial liver enzyme. Carglumic acid acts as a CPS 1 activator   in NAGS deficiency patients , thereby facilitating ammonia detoxification and urea production by removing the block in the urea cycle

Carglumic Acid (Carbaglu®) is indicated for adjunctive therapy in the treatment of acute hyperammonemia due to NAGS deficiency, propionic acidemia (PA) or methylmalonic acidemia (MMA), and maintenance therapy of chronic hyperammonemia due to the deficiency of the hepatic enzyme NAGS.


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

Acute Hyperammonemia due to N-acetylglutamate Synthase (NAGS) Deficiency

APPROVAL CRITERIA: Carglumic Acid (Carbaglu®) is medically necessary when all of the following are met:

  1. Diagnosis of acute hyperammonemia due to N-acetylglutamate synthase (NAGS) deficiency; and 
  2. Medication will be used as adjunctive therapy to other ammonia lowering therapies (e.g., protein restriction, ammonia scavengers, dialysis) 
  3. Prescribed by or in consultation with a provider who specializes in the treatment of metabolic disorders

Authorization duration: 3 months

Acute Hyperammonemia due to Propionic Acidemia (PA) or Methylmalonic Acidemia (MMA)

APPROVAL CRITERIA: Carglumic Acid (Carbaglu®) is medically necessary when all of the following are met:

  1. Diagnosis of acute hyperammonemia due to propionic acidemia (PA) or methylmalonic acidemia (MMA); and
  2. Medication will be used as adjunctive therapy to other ammonia lowering therapies (e.g., intravenous glucose, insulin, protein restriction, dialysis); and
  3. Patient's plasma ammonia level is greater than or equal to 50 micromol/L; and
  4. Medication will be used for a maximum duration of 7 days; and
  5. Prescribed by or in consultation with a provider who specializes in the treatment of metabolic disorders

Authorization duration: 3 months

Chronic Hyperammonemia due to N-acetylglutamate Synthase (NAGS) Deficiency

INITIAL CRITERIA: Carglumic Acid (Carbaglu®) is medically necessary when all of the following are met:

  1. Diagnosis of chronic hyperammonemia due to N-acetylglutamate synthase (NAGS) deficiency; and
  2. NAGS deficiency has been confirmed by genetic/mutational analysis; and
  3. Medication will be used as maintenance therapy; and
  4. Prescribed by or in consultation with a provider who specializes in the treatment of metabolic disorders

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: Carglumic acid (Carbaglu®) is medically necessary when there is documentation of positive clinical response to therapy (e.g., plasma ammonia level within the normal range).

Reauthorization duration: 2 years


N/A

Carbaglu® [package insert]. Lebanon NJ. Recordati Rare Diseases, Inc. January 2024. Available at: hhttps://www.carbaglu.com/wp-content/uploads/Carbaglu-Prescribing-Information-Current.pdf. Accessed October 10, 2024.

N-acetylglutamate synthetase deficiency. National organization for rare disorders. Available at: http://rarediseases.org/rare-diseases/n-acetylglutamate-synthetase-deficiency/. Accessed October 10, 2024.

Lee B. Urea cycle disorders: clinical features and diagnosis. UpToDate website. October 2023. Available at http://www.uptodate.com/. Accessed Accessed October 10, 2024.


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Off-Labe Use Rx01.33
Brand NameGeneric Name
Carbaglu®Carglumic Acid

Carbaglu®Carglumic acid
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
490
  
1/1/2025Rx.01.22CommercialVanHorn, LynnseyQ3-2024
Individuals, who are transfusion-dependent, receive excess iron with each transfusion.  In non-transfusion-dependent thalassemia (NTDT), elevated iron levels are related to suppression of hepcidin levels, increased intestinal iron absorption, and increased release of recycled iron from the reticuloendothelial system.  The excess iron accumulates in various tissues, including cardiac, liver, pulmonary, and endocrine glands, due to lack of an active mechanism to excrete iron.  The goal of iron chelation therapy in iron overload is to reduce iron levels, prevent complications, and reduce morbidity.

Deferasirox (Exjade®/ Jadenu®) is indicated for the treatment of transfusional hemosiderosis (chronic iron overload due to blood transfusions) in individuals who are 2 years of age or older and for the treatment of chronic iron overload in patients 10 years of age and older with NTDT syndromes and with a liver iron concentration (LIC) of at least 5 mg Fe per gram of dry weight (Fe/ g dw) and a serum ferritin greater than 300 mcg/L.

Deferiprone (Ferriprox®) is an iron chelator indicated for the treatment of patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate.

Deferasirox (Exjade®/Jadenu®) is an orally active chelator that is selective for iron (as Fe3+). It is a tridentate ligand that binds iron with high affinity in a 2:1 ratio. Although deferasirox has very low affinity for zinc and copper, there are variable decreases in the serum concentration of these trace metals after the administration of deferasirox. The clinical significance of these decreases is uncertain.

Deferiprone (Ferriprox®) is a chelating agent with an affinity for ferric ion (iron III). Deferiprone binds with ferric ions to form neutral 3:1 (deferiprone:iron) complexes that are stable over a wide range of pH values.


The intent of this policy is to communicate the medical necessity criteria for deferasirox (Exjade®/ Jadenu®) and deferiprone (Ferriprox®) as provided under the member's prescription drug benefit.

Chronic iron overload in blood transfusions dependent anemia

INITIAL CRITERIA: Deferasirox (Exjade®/Jadenu®) is medically necessary when ALL of the following are met:

  1. Diagnosis of chronic iron overload due to blood transfusions; and
  2. Member is 2 years of age or older; and
  3. Serum ferritin levels are consistently greater than 1000 mcg/L (as demonstrated with at least two lab values within two months prior to treatment)
  4. For Brand Exjade and Brand Jadenu only, inadequate response or inability to tolerate generic deferasirox

Initial authorization duration: 12 months
 
CONTINUATION CRITERIA: Deferasirox (Exjade®/Jadenu®) is medically necessary there is documentation of a decreased serum ferritin level compared with baseline level for transfusion dependent anemia.

Continuation duration: 2 years

INITIAL CRITERIA: Deferiprone (Ferriprox®) is medically necessary when all of the following are met:

  1. Diagnosis of transfusional iron overload due to Sickle Cell disease or other transfusion-dependent anemia; and
  2. Member is 3 years of age or older; and
  3. Inadequate response or inability to tolerate one of the following chelation therapy:
    1. Generic deferoxamine; or
    2. generic deferasirox; and
  4. For Brand Ferriprox tablets only, Inadequate response or inability to tolerate generic deferiprone tablets; and
  5. Current chelation therapy is inadequate

Initial authorization duration: 12 months

CONTINUATION CRITERIA: Deferiprone (Ferriprox®) is medically necessary when there is documentation of positive clinical response to therapy (e.g., decline in serum ferritin levels from baseline).

Continuation duration: 2 years

Chronic iron overload in non-transfusion-dependent Thalassemia Syndrome

INITIAL CRITERIA: Deferasirox (Exjade®/Jadenu®) is medically necessary when ALL of the following are met:

  1. Diagnosis of chronic iron overload in Non-Transfusion-Dependent Thalassemia Syndromes; and
  2. Member is 10 years of age or older; and
  3. Serum ferritin levels are consistently greater than 300 mcg/L and liver iron concentration (LIC) of at least 5 milligrams of iron per gram of liver dry weight (mg Fe/g dw) (as demonstrated with at least two lab values within 2 months prior to treatment)

Initial authorization duration: 12 months

CONTINUATION CRITERIA: Deferasirox (Exjade®/Jadenu®) is medically necessary when there is documentation of a decreased serum ferritin level compared with the baseline level or reduction in LIC (liver iron concentration) for non-transfusion dependent Thalassemia Syndrome

Continuation duration: 2 years

INITIAL CRITERIA: Deferiprone (Ferriprox®) is medically necessary when ALL of the following are met:

  1. Diagnosis of transfusional iron overload due to Thalassemia Syndrome; and
  2. Member is 3 years of age or older; and
  3. Inadequate response or inability to tolerate one of the following chelation therapy:
    1. Generic deferoxamine; or
    2. Generic deferasirox; and
  4. For Brand Ferriprox tablets only, Inadequate response or inability to tolerate generic deferiprone tablets; and
  5. Current chelation therapy is inadequate


Initial authorization: 12 months

CONTINUATION CRITERIA: Deferiprone (Ferriprox®) is medically necessary when there is documentation of positive clinical response to therapy (e.g., greater than or equal to 20% decline in serum ferritin levels from baseline).

Continuation duration: 2 years


Deferasirox (Exjade/ Jadenu)

Renal failure: Deferasirox can cause acute renal failure and death, particularly in patients with comorbidities and those who are in the advanced stages of their hematologic disorders. Deferasirox is contraindicated in adults and pediatric patients with eGFR less than 40 ml/min/1.73m2. Use caution in pediatric patients with eGFR between 40 and 60 ml/min/1.3m2. For patients with renal impairment (eGFR 40-60 ml/min/1.73m2) reduce starting dose by 50%. Measure serum creatinine and determine creatinine clearance (CrCl)prior to initiation of therapy and monitor renal function at least monthly thereafter. For patients with baseline renal impairment or increased risk of acute renal failure, monitor creatinine weekly for the first month, then at least monthly thereafter. Monitor serum ferritin monthly to evaluate for overchelation. Use the minimum dose to establish and maintain a low iron burden. Consider dose reduction, interruption, or discontinuation based on increases in serum creatinine. Interrupt deferasirox therapy when acute kidney injury is suspected and during volume depletion.

Hepatic failure: Deferasirox can cause hepatic injury including hepatic failure and death. Measure serum transaminases and bilirubin in all patients prior to initiating treatment, every 2 weeks during the first month, and at least monthly thereafter. Avoid use of deferasirox in patients with severe (Child-Pugh class C) hepatic impairment and reduce the dose in patients with moderate (Child-Pugh class B) hepatic impairment. Interrupt deferasirox therapy when acute liver injury is suspected and during volume depletion.

GI hemorrhage: Deferasirox can cause GI hemorrhages, which may be fatal, especially in elderly patients who have advanced hematologic malignancies and/or low platelet counts. Monitor patients and discontinue deferasirox for suspected GI ulceration or hemorrhage.

Deferiprone (Ferriprox)

Agranulocytosis/Neutropenia: Deferiprone can cause agranulocytosis that can lead to serious infections and death. Neutropenia may precede the development of agranulocytosis. Measure the absolute neutrophil count (ANC) before starting deferiprone therapy and monitor the ANC weekly during therapy. Interrupt deferiprone therapy if neutropenia develops. If infection develops, interrupt deferiprone and monitor the ANC more frequently. Advise patients taking deferiprone to report immediately any symptoms indicative of infection. For neutropenia, instruct the patient to immediately discontinue deferiprone and all other medications with potential to cause neutropenia. Obtain a complete blood count (CBC), white blood count (WBC corrected for the presence of nucleated red blood cells, ANC and a platelet count daily until recovery. For agranulocytosis, consider hospitalization and other clinically appropriate management.

Exjade (deferasirox) [package insert]. East Hanover NJ. Novartis Pharmaceuticals Corporation.  Revised July 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=3495a70c-870c-4968-940e-8baea152cf85&type=display. Accessed October 10, 2024.

Ferriprox (deferiprone) [package insert]. Rockville MD. ApoPharma USA, Inc.  Revised  May 2020.  Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=97f7bfcb-8666-464c-87b6-9621ceca5ee2&type=display. Accessed October 10, 2024.

 Gilroy RK. Wilson Disease. Available at: http://emedicine.medscape.com/article/183456-overview#a1. Accessed October 10, 2024.

Jadenu (deferasirox) [package insert]. East Hanover NJ. Novartis Pharmaceuticals Corporation. Revised July 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fee89140-fff1-4443-9f42-24ac004fcda1. Accessed October 10, 2024.

 Mir M. Transfusion induced iron overload. Available at: http://emedicine.medscape.com/article/1389732-overview. Accessed October 10, 2024.

Musallam KM, Rivella S, Vichinsky E, Rachmilewitz. Non-transfusion-dependent thalassemias. Haematologica. June 2013;98:833-844. DOI: 10.3324/haematol.2012.066845
169/12/20249/11/20251/1/2025 1:12 AMNo presence informationsrv_ppsgw_P
Off-Label Use policy Rx.01.33
Brand NameGeneric Name
ExjadeDeferasirox
JadenuDeferasirox
Ferriprox
Deferiprone

Exjade®/Jadenu® and Ferriprox®deferasirox and deferiprone
442
  
10/1/2024Rx.01.131CommercialOyenusi, OluwadamilolaQ2-2024
Lomitapide a synthetic lipid-lowering agent, directly binds and inhibits microsomal triglyceride transfer protein, which resides in the lumen of the endoplasmic reticulum, thereby preventing the assembly of apo B-containing lipoproteins in enterocytes and hepatocytes. This inhibits the synthesis of chylomicrons and very low-density lipoprotein (VLDL). The inhibition of the synthesis of VLDL leads to reduced levels of plasma LDL-C.

Lomitapide (Juxtapid®) is indicated as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available, to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH).

Proprotein convertase subtilisin/ kexin type 9 (PCSK9) is a serine protease synthesized primarily by the liver and intestines.  PCSK9 promotes the degradation of low density lipoprotein (LDL) receptors, thus preventing them from being recycled back to the plasma membrane where they can bind more LDL. Inhibitors of PCSK9 increase recycling of LDL receptors which in turn increases the capacity to remove LDL cholesterol (LDL-C) from the blood. These agents are monoclonal antibodies administered subcutaneously.

Alirocumab (Praluent®) is indicated:
  • To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease.
  • As adjunct to diet, alone or in combination with other low-density lipoprotein cholesterol (LDL-C)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C.
  • As an adjunct to other LDL-C-lowering therapies in adult patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C. 
  • As an adjunct to diet and other LDL-C-lowering therapies in pediatric patients aged 8 years and older with HeFH to reduce LDL-C.
Evolocumab (Repatha®) is indicated:
  • in adults with established cardiovascular disease (CVD) to reduce the risk of myocardial infarction, stroke, and coronary revascularization.
  • As adjunct to diet, alone or in combination with other low-density lipoprotein cholesterol (LDL-C)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C.
  • As an adjunct to diet and other LDL-C-lowering therapies in pediatric patients aged 10 years and older with HeFH, to reduce LDL-C. 
  • As an adjunct to other LDL-C-lowering therapies in adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C.
According to current guidelines, HMG-CoA reductase inhibitors (statins) are the mainstay of pharmacologic therapy for treating elevated LDL-C for both primary and secondary prevention of atherosclerotic cardiovascular disease.  Lifestyle modifications are a critical component of treating elevated LDL-C and should be used in conjunction with pharmacologic therapy.  

Clinical trials of PCSK9 inhibitors demonstrated reductions in LDL-C approximately 50-60%.  Reauthorization criteria will include a reduction from baseline of 25% or greater, which will assess adherence with the medication.

Bempedoic acid (Nexletol™) is an adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) by inhibition of cholesterol synthesis in the liver.  ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway.  Bempedoic ​acid and its active metabolite, ESP15228, require coenzyme A (CoA) activation by very long-chain acyl-CoA synthetase 1 (ACSVL1) to ETC-1002-CoA and ESP15228-CoA, respectively.  ACSVL1 is expressed primarily in the liver.  Inhibition of ACL by ETC-1002-CoA results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of low-density lipoprotein receptors.

Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine.  The molecular target of ezetimibe has been shown to be the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols.  Ezetimibe localizes at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver.  This causes a reduction of hepatic cholesterol stores and an increase in LDL receptors, resulting in clearance of cholesterol from the blood.

Bempedoic acid (Nexletol™) and bempedoic acid/ezetimibe (Nexlizet™) is indicated: 
  • To reduce the risk of myocardial infarction and coronary revascularization in adults who are unable to take recommended statin therapy (including those not taking a statin) with:
    • established cardiovascular disease (CVD), or
    • a high risk for a CVD event but without established CVD
  • As an adjunct to diet, in combination with other low-density lipoprotein cholesterol (LDL-C) lowering therapies, or alone when concomitant  LDL-C lowering therapy is not possible, to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH)

The intent of this policy is to communicate the medical necessity criteria for lomitapide (Juxtapid®), alirocumab (Praluent®), evolocumab (Repatha®), bempedoic acid (Nexletol™), and bempedoic acid/ezetimibe (Nexlizet™) as provided under the member's prescription drug benefit.

Hypercholesterolemia
 
INITIAL CRITERIA: Lomitapide (Juxtapid®) is approved when ALL of the following are met:

  1. Diagnosis of Homozygous Familial Hypercholesterolemia; and
  2. Used as an adjunct to lipid lowering treatments and a low-fat diet with ONE of the following:
    1. Genetic confirmation of 2 mutant alleles at the LDL receptor, Apo B, PCSK9, or LDL receptor adaptor protein 1 (i.e. LDLRAP1 or ARH); or
    2. Untreated LDL-C > 500mg/dL or treated LDL cholesterol ≥ 300mg/dL with either of the following:
      1. Cutaneous or tendinous xanthoma prior to 10 years of age, or
      2. Elevated LDL cholesterol prior to lipid-lowering therapy consistent with HeFH in both parents; AND
  3. ONE of the following:
    1. Inadequate response to one of the following medications in combination with ezetimibe:
      1. Simvastatin (daily doses ≥ 40mg); or
      2. Atorvastatin (daily doses ≥ 20mg); or
      3. Rosuvastatin (daily doses ≥ 10mg); or
    2. Member has experience ONE of the following:
      1. Rhabdomyolysis or muscle symptoms with creatine kinase (CK) elevations > 10 times upper limit of normal (ULN) on any statin; or
      2. Myalgia (muscle symptoms without CK elevations) or myositis (muscle symptoms with CK elevations < 10 times ULN) with TWO statins; AND
  4. Inadequate response or inability to tolerate evolocumab (Repatha®); and
  5. Not used in combination with a PCSK9 inhibitor; and
  6. Prescribed by or in consultation with one of the following:
    1. Cardiologist; or
    2. Endocrinologist; or
    3. Lipid specialist

Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Lomitapide (Juxtapid®) is re-approved when ALL of the following are met:

  1. One of the following:
    1. Member continues to receive other lipid-lowering therapy (e.g., statin, ezetimibe); or
    2. Member has an inability to take other lipid-lowering therapy (e.g., statin, ezetimibe); and
  2. Reduction in LDL-C of at least 25% from baseline while on therapy; and
  3. Prescribed by or in consultation with one of the following:
    1. Cardiologist; or
    2. Endocrinologist; or
    3. Lipid specialist; and
  4. Not used in combination with a PCSK9 inhibitor

Reauthorization duration: 12 months

INITIAL CRITERIA: Alirocumab (Praluent®) is approved when ALL of the following are met:

  1. Diagnosis of ONE of the following:
    1. Hyperlipidemia; or
    2. Homozygous familial hypercholesterolemia and one of the following:
      1. Diagnosis confirmed by genetic test; or
      2. Untreated LDL-C >500mg/dL with either of the following:
        1. Cutaneous or tendinous xanthoma prior to 10 years of age; or 
        2. Elevated LDL cholesterol prior to lipid-lowering therapy consistent with HeFH in both parents; or
    3. Atherosclerotic cardiovascular disease as diagnosed by either stress test, angiography, atherosclerotic event (e.g., MI, angina, stroke, claudication, carotid stenosis) or arterial intervention for atherosclerotic diseases (e.g., coronary, peripheral, carotid); and
  2. ONE of the following:
    1. LDL-C greater than or equal to 55mg/dL with atherosclerotic cardiovascular disease (ASCVD) while on maximally tolerated statin therapy within the last 120 days; or
    2. LDL-C greater than or equal to 100mg/dL without atherosclerotic cardiovascular disease (ASCVD) while on maximally tolerated statin therapy within the last 120 days; or
    3. Inability to tolerate statin therapy as documented by ONE of the following:
      1. Member has rhabdomyolysis or symptoms with creatine kinase (CK) exceeding 10 times the upper limit of normal (ULN) on any statin; or
      2. ONE of the following with TWO statins:
        1. Myalgia (no CK elevation); or
        2. Myositis (CK less than 10 times ULN); or
        3. Hepatotoxicity from statin use (increase AST/ALT exceeding 3 times ULN); or
      3. Liver disease documented by Child Pugh A or worse or AST/ALT exceeding 3 times ULN for at least 6 weeks; and
  3. Inadequate response or inability to tolerate evolocumab (Repatha®)

Initial authorization duration: 6 months.

REAUTHORIZATION CRITERIA: Alirocumab (Praluent®) is re-approved when there is a sustained reduction in LDL-C of at least 25% since initiation of therapy.

Reauthorization duration: 12 months

INITIAL CRITERIA: Evolocumab (Repatha®) is approved when ALL of the following are met:

  1. Diagnosis of ONE of the following:
    1. Hyperlipidemia; or
    2. Homozygous familial hypercholesterolemia and one of the following:
      1. Diagnosis confirmed by genetic test; or
      2. Untreated LDL-C >500mg/dL with either of the following:
        1. Cutaneous or tendinous xanthoma prior to 10 years of age; or
        2. Elevated LDL cholesterol prior to lipid-lowering therapy consistent with HeFH in both parents; or
    3. Atherosclerotic cardiovascular disease as diagnosed by either stress test, angiography, atherosclerotic event (e.g., MI, angina, stroke, claudication, carotid stenosis) or arterial intervention for atherosclerotic disease (e.g., coronary, peripheral, carotid); AND
  2. ONE of the following:
    1. LDL-C greater than or equal to 55mg/dL with atherosclerotic cardiovascular disease (ASCVD) while on maximally tolerated statin therapy within the last 120 days; or
    2. LDL-C greater than or equal to 100mg/dL without atherosclerotic cardiovascular disease (ASCVD) while on maximally tolerated statin therapy within the last 120 days; or
    3. Inability to tolerate statin therapy as documented by ONE of the following:
      1. Member had rhabdomyolysis or symptoms with creatine kinase (CK) exceeding 10 times the upper limit of normal (ULN) on any statin; or
      2. ONE of the following with TWO statins:
        1. Myalgia (no CK elevation); or
        2. Myositis (CK less than 10 times ULN; or
        3. Hepatotoxicity from statin use (increased AST/ALT exceeding 3 times ULN); OR
      3. Liver disease documented by Child Pugh A or worse OR AST/ALT exceeding 3 times ULN for at least 6 weeks

Initial Authorization duration: 6 months


REAUTHORIZATION CRITERIA:  Evolocumab (Repatha®) is re-approved when there is a sustained reduction in LDL-C of at least 25% since initiation of therapy

Reauthorization duration: 12 months

       

INITIAL CRITERIA: Bempedoic acid (Nexletol™), bempedoic acid/ezetimibe (Nexlizet™) is approved when ALL of the following are met:
  1. ONE of the following:
    1. Heterozygous familial hypercholesterolemia (HeFH); or
    2. Primary hyperlipidemia; and
  2. One of the following:
    1. LDL-C greater than or equal to 55mg/dL with atherosclerotic cardiovascular disease (ASCVD) while on maximally tolerate statin therapy within the last 120 days; or
    2. LDL-C greater than or equal to 100mg/dL without atherosclerotic cardiovascular disease (ASCVD) while on maximally tolerate statin therapy within the last 120 days; or
    3. Inability to tolerate statin therapy as documented by ONE of the following:
      1. Member has rhabdomyolysis or symptoms with creatine kinase (CK) exceeding 10 times the upper limit of normal (ULN) on any statin; or
      2. ONE of the following with TWO statins:
        1. Myalgia (no CK elevation); or
        2. Myositis (CK less than 10 times ULN); or
        3. Hepatotoxicity from statin use (increase AST/ALT exceeding 3 times ULN); or
      3. Liver disease documented by Child Pugh A or worse or AST/ALT exceeding 3 times ULN for at least 6 weeks; and
  3. ONE of the following:
    1. Member has been receiving at least 12 consecutive weeks of ezetimibe (Zetia®) therapy as adjunct to maximally tolerated statin therapy; or
    2. Member has contraindication or intolerance to ezetimibe (Zetia®)

 
Initial Authorization duration: 6 months
 
REAUTHORIZATION CRITERIA: Bempedoic acid (Nexletol™), Bempedoic acid/ezetimibe (Nexlizet™) is re-approved when ALL of the following are met:

  1. Member demonstrates positive clinical response to therapy (e.g., reduction in LDL-C levels); and
  2. ONE of the following:
    1. Member continues to receive other lipid-lowering therapy (e.g., statins, ezetimibe) at the maximally tolerated dose; or
    2. Member has inability to tolerate other lipid-lowering therapy (e.g., statins, ezetimibe)

Reauthorization duration: 12 months


Established cardiovascular disease (CVD) or high risk for a CVD event but without established CVD
 
INITIAL CRITERIA: Bempedoic acid (Nexletol™), bempedoic acid/ezetimibe (Nexlizet™) is approved when ALL of the following are met:

  1. ONE of the following:
    1. Member has established cardiovascular disease (CVD) (e.g., coronary artery disease, symptomatic peripheral arterial disease, cerebrovascular atherosclerotic disease); or
    2. Member is at high risk for a CVD event but without established CVD [e.g., diabetes mellitus (type 1 or type 2) in females over 65 years of age or males over 60 years of age]; and
  2. One of the following:
    1. LDL-C greater than or equal to 55 mg/dL with atherosclerotic cardiovascular disease (ASCVD) while on maximally tolerate statin therapy within the last 120 days; or
    2. LDL-C greater than or equal to 100 mg/dL without ASCVD while on maximally tolerate statin therapy within the last 120 days; and
    3. Inability to tolerate statin therapy as documented by ONE of the following:
      1. Member has rhabdomyolysis or symptoms with creatine kinase (CK) exceeding 10 times the upper limit of normal (ULN) on any statin; or
      2. ONE of the following with TWO statins:
        1. Myalgia (no CK elevation); or
        2. Myositis (CK less than 10 times ULN); or
        3. Hepatotoxicity from statin use (increase AST/ALT exceeding 3 times ULN); or
      3. Liver disease documented by Child Pugh A or worse or AST/ALT exceeding 3 times ULN for at least 6 weeks; and
  3. One of the following:
    1. Member has been receiving at least 12 consecutive weeks of ezetimibe (Zetia®) therapy as adjunct to maximally tolerated statin therapy; or
    2. Member has contraindication or intolerance to ezetimibe (Zetia®)

Initial Authorization duration: 6 months
 
REAUTHORIZATION CRITERIA: Bempedoic acid (Nexletol™), Bempedoic acid/ezetimibe (Nexlizet™) is re-approved when ALL of the following are met:

  1. Member demonstrates positive clinical response to therapy (e.g., reduction in LDL-C levels); and
  2. ONE of the following:
    1. Member continues to receive other lipid-lowering therapy (e.g., statins, ezetimibe) at the maximally tolerated dose; or
    2. Member has inability to tolerate other lipid-lowering therapy (e.g., statins, ezetimibe)

Reauthorization duration: 12 months


JUXTAPID® (lomitapide): WARNING: RISK OF HEPATOTOXICITY

JUXTAPID can cause elevations in transaminases. 
  • Measure alanine and aspartate aminotransferases (ALT, AST), alkaline phosphatase, and total bilirubin before initiating treatment and then ALT and AST regularly as recommended.
  • During treatment, adjust the dose of JUXTAPID if the ALT or AST is ≥3 times the upper limit of normal (ULN).
  • Discontinue JUXTAPID for clinically significant liver toxicity. 
JUXTAPID increases hepatic fat (hepatic steatosis) with or without concomitant increases in transaminases. 
  • Hepatic steatosis associated with JUXTAPID may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis.

Because of the risk of hepatotoxicity, JUXTAPID is available only through a restricted program called the JUXTAPID REMS Program. Prescribe JUXTAPID only to patients with a clinical or laboratory diagnosis consistent with HoFH. The safety and effectiveness of JUXTAPID have not been established in patients with hypercholesterolemia who do not have HoFH.

Farnier M, Bruckert E. Severe familial hypercholesterolemia: Current and future management. Arch Cardiovasc Dis. 2012 Dec; 105(12):656-65. Accessed July 31, 2024.


Goldberg AC, Hopkins PN, Toth PP, et al. Familial hypercholesterolemia: screening, diagnosis, and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidology. 2011;5:S1-S8. Accessed July 31, 2024.


Grundy SM, Cleeman JI, Merz NB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation. 2004; 110:227-39. Accessed July 31, 2024.


Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for the patient-centered management of dyslipidemia: Part 1- full report. J Clin Lipidology. 2015;9:129-69. Accessed July 31, 2024.


Juxtapid® (lomitapide) [prescribing information.] Cambridge, MA. Aegerion Pharmaceuticals. September 2020. Available at: http://juxtapidpro.com/prescribing-information. Accessed July 31, 2024.


Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis. 2012 Aug; 223(2):262-8. Accessed July 31, 2024.


Grundy SM, Stone NJ, Bailey AL, Yeboah J, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018. Available from: https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000000624. Accessed July 31, 2024.


Visser ME, Witztum JL, Stroes ES, et al. Antisense oligonucleotides for the treatment of dyslipidaemia. Eur Heart J. 2012 Jun; 33(12):1451-8. doi: 10.1093/eurheartj/ehs084. Epub 2012 May 24.


Lambert G, Sjouke B, Choque B, Kastelein JJP, Hovingh GK. The PCSK9 decade. J Lipid Res. 2012; 53(12): 2515-24. DOI: 10.1194/jlr.R026658. Accessed July 31, 2024.


Farnier M. PCSK9: From discovery to therapeutic applications. Arch Cardiovascular Dis. 2014; 107: 58-66. DOI: 10.1016/j.acvd.2013.10.007. Accessed July 31, 2024.


Goldberg AC, Hopkins PN, Toth PP, et al. Familial hypercholesterolemia: screening, diagnosis, and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidology. 2011;5:S1-S8. Accessed July 31, 2024


Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for the patient-centered management of dyslipidemia: Part 1- full report. J Clin Lipidology. 2015;9:129-69. Accessed July 31, 2024.


Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Daly Jr DD, DePalma SM, Minissian, MB, Orringer CE, Smith Jr SC, 2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Exper Decision Consensus Pathways. Journal of the American College of Cardiology (2017), doi: 10.1016/j.jacc.2017.07.745. Accessed July 31, 2024.


Nexletol™ (bempedoic acid) [prescribing information]. Ann Arbor, MI: Esperion Therapeutics, Inc.; March 2024. Available from: https://pi.esperion.com/nexletol/nexletol-pi.pdf. Accessed July 31, 2024.


Nexlizet™ (bempedoic acid and ezetimibe) [prescribing information]. Ann Arbor, MI: Esperion Therapeutics, Inc.; March 2024. Available from: https://pi.esperion.com/nexlizet/nexlizet-pi.pdf. Accessed July 31, 2024.


Praluent® (alirocumab) [package insert]. Bridgewater, NJ. Sanofi-Aventis US LLC. March 2024.  Available from: http://products.sanofi.us/praluent/praluent.pdf. Accessed July 31, 2024.


Repatha® (evolocumab) [package insert]. Thousand Oaks, CA. Amgen Inc. September 2021. Available from: https://www.pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/repatha/repatha_pi_hcp_english.pdf. Accessed July 31, 2024.


Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce cardiovascular risk in adults: a report of the American College of Cardiology/ American Heart Association Task Force on practice guidelines. Circulation. 2013. https://doi.org/10.1161/01.cir.0000437738.63853.7a. Accessed July 31, 2024.


Varghese MJ. Familial hypercholesterolemia: a review. Ann Pediatr Cardiol. 2014;7:107-17. Accessed July 31, 2024.



167/1/20246/6/202510/1/2024 1:12 AMNo presence informationsrv_ppsgw_P
Off-Label Use Rx.01.33
Brand nameGeneric name
Juxtapid®Lomitapide
Praluent®alirocumab
Repatha®evolocumab
Nexletol™Bempedoic acid
Nexlizet™Bempedoic acid/ezetimibe


Juxtapid®, Praluent®, Repatha®, Nexletol™, Nexlizet™lomitapide, alirocumab, evolocumab, bempedoic acid, bempedoic acid/ezetimibe
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

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Rx.01.33 Off-Label Use 
Cholbam®cholic acid
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
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.

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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
491
  
1/1/2025Rx.01.218CommercialVanHorn, LynnseyQ3-2024
The Continuous Glucose Monitors (CGMs) are indicated for use in individuals with type 1 diabetes who require insulin and need to be monitored for unexplained glycemic fluctuations and hypoglycemic unawareness. Hypoglycemic unawareness is the inability of an individual to notice and recognize symptoms of hypoglycemia while they are experiencing them.

CGMs devices are considered an adjunct to be used with a traditional blood glucose monitor. These adjunctive devices allow individuals to track glucose levels and detect episodes of high and low blood sugar in real-time on an ongoing basis. The device consists of a disposable subcutaneous sensor, an external transmitter, and an external receiver (monitor), which can be a stand-alone device or built into an insulin pump. Sensors are worn as indicated by the device manufacturer in accordance with US Food and Drug Administration (FDA) labeling and are replaced on an ongoing basis.

Depending on the device sensor longevity capability, a CGMs sensor measures interstitial glucose levels for 6 to 14 days. Use of this device requires the glucose sensor to be implanted subcutaneously, usually in the abdomen or in an area above the buttocks. The transmitter is connected to the sensor by an adhesive patch, and glucose signals are sent from the sensor to the receiver every five minutes. Interstitial glucose values appear on the receiver or mobile device, where they can be read and reviewed by the individual. This data may be stored and downloaded for analysis. CGMs devices also allow for customization of threshold settings, such as alarms, to detect high and low glucose levels.

The FDA has approved several CGMs devices to assist in analyzing glycemic trends in the ongoing evaluation and management of individuals with diabetes. The FDA requires that alterations to an individual's insulin dosage or therapy are made only after confirmation of blood glucose levels with a traditional blood glucose monitor.

The intent of this policy is to communicate the medical necessity criteria for Continuous Glucose Monitors (Dexcom®, Medtronic®, Freestyle Libre) as provided under the member's prescription drug benefit.



INITIAL CRITERIA: Continuous glucose monitor (CGM) products (receivers, transmitters and sensors) are medically necessary when ALL of the following are met:

  1. Diagnosis of diabetes; and
  2. Member is adherent to current diabetes treatment plan and participates in ongoing diabetes education and support; and
  3. One of the following:
    1. Member is treated with insulin; or
    2. Member is non-insulin treated and experiences significant hypoglycemia (e.g., recurrent, unexplained, severe [generally blood glucose levels <50 mg/dL] hypoglycemia or hypoglycemic unawareness); and
  4. For Freestyle Libre only, submission of documentation (e.g., chart notes) or paid claim history showing member had a minimum 90-day trial of Dexcom within the last 180 days

Initial authorization duration: 2 years.

REAUTHORIZATION CRITERIA: Continuous glucose monitor (CGM) products (receivers, transmitters and sensors) are medically necessary when ALL of the following are met:

  1. Documentation that of a positive clinical response as evidenced by ONE of the following:
    1. Improvement in glycemic control (e.g., lower and/or maintain A1C levels); or
    2. Reduction or improvement in hypoglycemic events; and
  2. For Freestyle Libre only, submission of documentation (e.g., chart notes) or paid claim history showing member had a minimum 90-day trial of Dexcom within the last 180 days

Reauthorization duration: 2 years


None

Dexcom® CGM. Available at: https://www.dexcom.com/continuous-glucose-monitoring. Accessed April 17, 2024.

Freestyle Libre® CGM. Available at: https://www.freestyle.abbott/us-en/home.html. Accessed April 17, 2024.

Medtronic® CGM. Available at: https://www.medtronicdiabetes.com/treatments/continuous-glucose-monitoring. Accessed April 17, 2024.

Weinstock, R. Management of blood glucose in adults with type 1 diabetes mellitus. UpToDate website. Updated February 2021 www.uptodate.com. 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
Dexcom® line of productsMedtronic® line of productsFreestyle® line of products
Dexcom® G5 Receivers
Dexcom® G6 Receivers
Dexcom® G7 Receiver
Dexcom® G5 Sensors
Dexcom® G6 Sensors
Dexcom® G7 Sensor
Dexcom® G5 Transmitter Kit
Dexcom® G6 Transmitter Kit

Guardian™ Connect Transmitter
Guardian™ Sensor
Enlite® Sensor
Eversense® Sensor/Holder

 

Freestyle Libre® 14 Day Reader
Freestyle Libre® 14 Day Sensor
Freestyle Libre® 2 Reader
Freestyle Libre® 2 Sensor
Freestyle Libre® 3 Sensor




Dexcom®, Medtronic®, Freestyle LibreContinuous Glucose Monitors
492
  
1/1/2025Rx.01.291CommercialVanHorn, LynnseyQ3-2024

The Company utilizes a tiered cost-sharing structure for medications covered under the pharmacy benefit.  Members should refer to their benefit booklet for more information.

Cost Share Exceptions for Women's Preventive Services

The services listed in this policy are considered preventive care services when the criteria in this policy are met, when they are identified as preventive services in the Company's benefit contracts and when they are mandated by state or federal law. This policy supports the Women's Preventive Services (WPS) provision of Patient Protection and Affordable Care Act (PPACA). These products are available without cost-sharing with a prescription when provided by a participating retail or mail-order pharmacy.

Based on the Women's Preventive Services (WPS) provision of Patient Protection and Affordable Care Act (PPACA) recommendation the following products are available at zero-dollar cost-share. All medications refer to generic, single ingredient products unless otherwise noted.​


Category

Recommendation

Medication

CONTRACEPTIVES

The contraceptive methods for women currently identified by the FDA include: (1) sterilization surgery for women; (2) surgical sterilization implant for women; (3) implantable rod; (4) IUD copper; (5) IUD with progestin; (6) shot/injection; (7) oral contraceptives (combined pill); (8) oral contraceptives (progestin only); (9) oral contraceptives extended/continuous use; (10) patch; (11) vaginal contraceptive ring; (12) diaphragm; (13) sponge; (14) cervical cap; (15) condom; (16) spermicide; (17) emergency contraception; and (18) emergency contraception (Ella)

injection/shot, oral contraceptives, etonogestrel-ethinyl estradiol vaginal ring, diaphragms, sponge, cervical cap, condom, spermicide, emergency contraceptive, Ella®, Phexxi®. [Note: IUDs and implantable products are covered under the medical benefit. See referenced policy]


Certain contraceptives have additional indications that are not addressed by the preventative care measure or have generic alternatives. Thus, the plan employs medical management to administer the requirements. The policy below outlines the process by which an exception can be obtained for medications that may apply to the WPS provision of the PPACA but are not coded as $0 at the point-of-sale.



The intent of this policy is to communicate the medical necessity criteria for contraceptives formulary exception requests as provided under the member's prescription drug benefit.

Non-formulary Exceptions:

A non-formulary contraceptive is medically necessary for $0 cost-share when BOTH of the following are met:

  1. The drug is described as a preventative medication identified by the Women's Preventive Services provision of the Patient Protection and Affordable Care Act (PPACA); and
  2. The prescriber has provided documentation indicating the requested product is medically necessary

Authorization duration: 1 year

$0 Cost-Share Override

An exception to allow $0 cost-share for contraceptives covered on the formulary is medically necessary when BOTH of the following are met:

  1. The drug is described as a preventative medication identified by the Women's Preventive Services provision of the Patient Protection and Affordable Care Act (PPACA); and
  2. The prescriber has provided documentation indicating the requested product is medically necessary

Authorization duration: 1 year

*This policy does not apply to the Premium Formulary.

Cigarette Smoking and Serious Cardiovascular Events


Women over 35 years old who smoke should not use combination oral contraceptives.


Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use.


Women’s Preventive Services Guideline Available at: https://www.hrsa.gov/womens-guidelines. Accessed October 10, 2024.
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Rx.01.33 Off Label Use

Rx.01.76 Quantity Level Limits for Pharmaceutical Covered under the Pharmacy Benefit

00.06.02 Preventive Care Services Medical Policy ​


N/A
N/AN/A
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
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Non-FDA approved Products Rx.04.2

Off-Label Use Rx.01.33

Convenience Packs
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Independence Blue Cross is a subsidiary of Independence Health Group, Inc. — independent licensees of the Blue Cross and Blue Shield Association, serving the health insurance needs of Philadelphia and southeastern Pennsylvania.