Notification



Notification Issue Date:



Policy Attachment


Attachment to Policy # 08.00.13v


Attachment:A

Policy #:08.00.13v

Description:Dosing and Frequency Requirements

Title:Immune Globulin Intravenous (IVIG), Subcutaneous (SCIG)



DOSING AND FREQUENCY REQUIREMENTS FOR INTRAVENOUS IMMUNE GLOBULIN (IVIG) AND SUBCUTANEOUS IMMUNE GLOBULIN (SCIG)

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this Policy to ensure consistency with the most recently published recommendations for the use of IVIG and SCIG. Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the US Food and Drug Administration (FDA), drug manufacturers' guidelines, Company-recognized authoritative pharmacology compendia, or published peer-reviewed clinical research. The professional provider must supply supporting documentation (ie, published peer-reviewed literature) in order to request coverage for an amount of IVIG and SCIG outside of the Dosing and Frequency Requirements listed in this policy. For a list of Company-recognized pharmacology compendia and criteria for peer-reviewed clinical research, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of these drugs. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the precertification process. The Company reserves the right to conduct post-payment review and audit procedures for any claims submitted for IVIG and SCIG.

DOSING AND FREQUENCY REQUIREMENTS FOR INTRAVENOUS IMMUNE GLOBULIN (IVIG)

Examples of IVIG therapy include AscenivTM, Bivigam®, Carimune NF®, Flebogamma®, Gammagard Liquid®, Gammagard S/D®, Gammaked®, Gammaplex®, Gamunex-C®, Octagam®, Panzyga®, Privigen®

DERMATOLOGIC
Indication
Dosing and Frequency
Autoimmune mucocutaneous blistering disease for the following biopsy-proven conditions: pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid (cicatricial pemphigoid), benign mucous membrane pemphigoid, with or without mention of ocular movement, epidermolysis bullosa acquisita Induction and Maintenance: 2 g/kg per cycle (total dose divided equally, each given on 3 to 5 consecutive days). Initial frequency is generally 1 cycle every 3 to 4 weeks (or every 2 weeks for ocular cicatricial pemphigoid). The frequency or dose may be slowly reduced after there is effective control of the disease (eg, increase intervals to 6, 8, 10, 12, 14, and 16 weeks. Last cycle given after a 16-week interval).3, 86, 95, 97, 127, 140
IVIG must be used only for short-term therapy.79
Erythema multiforme major (Stevens-Johnson syndrome and toxic epidermal necrolysis)Induction:
Adults: 2-3 g/kg over a period of 2 to 5 days.4, 87, 172, 180
Pediatric: 1.5-2 g/kg per day for 3 days.5, 180

Maintenance: Maintenance therapy is not warranted. 179
Scleromyxedema Induction and Maintenance: 2 g/kg (total dose, divided over 2-5 days) and repeated every 4-12 weeks. Reassess after 6 months of therapy. 6, 7, 8, 70, 102, 182, 197

HEMATOLOGIC
Indication
Dosing and Frequency
Acute idiopathic thrombocytopenic purpura (ITP)Induction:
Adult: 1-2 g/kg administered over 1 to 5 days.12 , 183, 184

Pediatric: 1 g/kg/day for 1 to 2 days. 12, 80, 184

Maintenance: Maintenance therapy is not warranted.
Anemia, autoimmune hemolytic (AIHA)Induction and Maintenance: 0.4-1 g/kg per day for 5 days, and may repeat every 3 weeks.14, 18, 88
Anemia due to parvovirus B19 infection Induction:
In individuals with chronic infections with anemia, administer 0.4 g/kg for 5-10 days or 1 g/kg for 3 days.25, 42

In HIV-infected individuals with pure red cell aplasia related to B19 coinfection, administer 1-2 g/kg/day for 2-5 days.25, 42

Maintenance: 0.4 g/kg every 4 weeks.25, 42
Chronic refractory idiopathic thrombocytopenic purpura (ITP)Induction:
Adult: 400 mg/kg daily for 2 to 5 days. 1 Alternatively, 1 to 2 g/kg divided into 2 doses and given over 2 consecutive days. 1, 81

Pediatric: 0.8-1 g/kg with a second dose given in 48 hours if platelet count has not increased to above 20 X 109/L. 12

Maintenance: If the response is inadequate, 400 mg/kg may be administered as a single maintenance dose once every several weeks. In some individuals, it may be necessary to increase the maintenance dose to 800 mg/kg or 1 g/kg. 1, 81, 82
Idiopathic thrombocytopenic purpura (ITP) during pregnancyInduction: 400 mg/kg per day for three to five days.11, 12, 168

Maintenance: Peer-reviewed literature does not speak to Maintenance therapy; therefore, dosing is not warranted.
Fetal/neonatal alloimmune thrombocytopenia Induction and Maintenance:
For antenatal treatment: 1 g/kg weekly. This treatment is initiated around 20 weeks of pregnancy and no later than 30 weeks.12, 185

For neonatal treatment: 1 g/kg per day for 1 to 3 days.13
Rh and ABO incompatibility (moderate to severe) as treatment in addition to phototherapy to prevent or delay exchange transfusion in neonatesNeonatal Induction: 500-1000 mg/kg over 2 to 4 hours, given every 12 hours, up to 2 doses.44, 45, 46, 47, 48, 49, 131

Neonatal Maintenance: There is an absence of peer-reviewed evidence and clinical consensus regarding Maintenance therapy; therefore, dosing is not warranted.
Systemic Capillary Leak Syndrome (SCLS) or Clarkson's Disease Induction: 2 g/kg/month 188, 189, 190, 191

Maintenance: 0.4–2 g/kg/month 188, 189, 191 Taper to the lowest effective dose 179
Retreatment: If relapse occurs, administer up to 2 g/kg 188

IMMUNODEFICIENCY SYNDROMES
Indication
Dosing and Frequency
Acquired (secondary) hypogammaglobulinemia in oncologic conditionsChimeric antigen receptor (CAR) T cell therapy (e.g., tisagenlecleucel [Kymriah™], axicabtagene ciloleucel [Yescarta™]) acquired hypogammaglobulinemia
Induction and Maintenance: 500 mg/kg every 3 to 4 weeks to reach serum IgG levels greater than 400 mg/dL. 203, 204

Chronic lymphocytic leukemia (CLL) with associated hypogammaglobulinemia
Induction and Maintenance: 200-400 mg/kg every 3 to 4 weeks for 1 year. After 1 year, treatment should be continued to maintain IgG trough levels >500 mg/dL. 1, 14, 18, 37, 121, 123, 133, 134, 152

Multiple myeloma
Induction and Maintenance: 0.4 g/kg every 3 to 4 weeks to reach serum IgG levels greater than 500 mg/dL.35, 139

Other malignant diseases with associated hypogammaglobulinemia in an individual who has a high risk of serious, recurrent bacterial infections
Induction: Single dose of 400 to 600 mg/kg.18, 37
Maintenance: 0.4 g/kg every 3-4 weeks with reevaluation every 4-6 months.18, 37
Acquired Von Willebrand disease associated with IgG-MGUS (monoclonal gammopathy of undetermined significance of the IgG Class) or antibody-mediated acquired Von Willebrand disease Induction: 1 g/kg daily for two days. 12, 160, 161

Maintenance: Maintenance therapy is not warranted.
Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (Wegener's granulomatosis, microscopic polyangiitis [MPA], Churg-Strauss syndrome)Induction: 2 g/kg (total dose, divided over 5 days). 165, 166, 186

Maintenance: There is an absence of peer-reviewed evidence and clinical consensus regarding Maintenance therapy; therefore, dosing is not warranted.
Autoimmune neutropenia Induction: 0.4-1 g/kg/day for 2-5 days. 12, 15, 16, 89, 90, 92

Maintenance: There is an absence of peer-reviewed evidence and clinical consensus regarding Maintenance therapy; therefore, dosing is not warranted.
Bone marrow transplantation Induction: 500 mg/kg weekly to day 90.17, 118

Maintenance: If severely hypogammaglobulinemic (IgG levels less than 400mg/dL) after day 90, administer 500 mg/kg monthly to day 360 post-transplantation. 17, 93
Catastrophic antiphospholipid syndrome (CAPS) Induction: 0.4 g/kg daily for 4-5 days. 144, 162, 163

Maintenance: Maintenance therapy is not warranted.
Coagulopathy due to acquired inhibitor of clotting factor VIII Induction and Maintenance: 1 g/kg/day for 2 days or 0.4 g/kg/day for 5 days followed by maintenance doses at intervals as clinically indicated to reduce inhibitor titers.12, 18, 19, 96, 151
Hematopoietic stem cell transplant (HSCT) for an adult, adolescent, or pediatric allogeneic stem cell transplant recipient who experiences severe hypogammaglobulinemia (IgG less than or equal to 400 mg/dL):
Within the first 100 days after transplant:
Induction and Maintenance:
Adult or adolescent: 500 mg/kg/week when serum IgG falls below 400 mg/dL.20, 94, 122
Pediatric: 400 mg/kg/month when serum IgG falls below 400 mg/dL.94

Beyond the first 100 days after transplant:
Induction and Maintenance:
Adult: 500 mg/kg every 3-4 weeks when serum IgG falls below 400 mg/dL.94, 122
Hyperimmunoglobulinemia E syndrome (HIES) 26, 27, 29 Induction and Maintenance: 300-600 mg/kg every 3 weeks, or 400-800 mg/kg every 4 weeks. Dosing intervals will be dependent on the catabolic rate of the individual's IgG but will generally be no more frequently than every 3 to 5 weeks. Treatment should be continued to maintain IgG trough levels >500 mg/dL.1, 2, 14, 18, 142, 154, 177, 178
Human immunodeficiency virus (HIV)--infected individuals to reduce significant bacterial infection Induction and Maintenance in Pediatric individuals: 400 mg/kg every 28 days.14, 18, 21, 75
Kawasaki disease (mucocutaneous lymph node syndrome)Induction: Single dose of 2 g/kg as soon as diagnosis is established.1, 15, 18, 22, 40 Children with persistent fever 36 hours after completion of an initial dose of IVIG can be treated with an additional single infusion of IVIG (2 g/kg) for a total cumulative IVIG dose of 4 g/kg.41, 142

Maintenance: Maintenance therapy is not warranted.
Neonatal hemochromatosis (neonatal alloimmune hepatitis)Administration to the pregnant woman:
Induction and Maintenance: 1 g/kg weekly from gestational week 18 until the end of gestation. 74, 91, 156, 157, 158

Administration to the neonate, combined with exchange transfusion:
Induction: 1 g/kg birth weight daily in the immediate one to two days after birth.74, 159

Maintenance: There is an absence of peer-reviewed evidence and clinical consensus regarding Maintenance therapy; therefore, dosing is not warranted.
Primary immunodeficiency disorders (PIDD) associated with defects in immunity 26, 27, 29 Induction and Maintenance: 300-600 mg/kg every 3 weeks, or 400-800 mg/kg every 4 weeks. Dosing intervals will be dependent on the catabolic rate of the individual's IgG but will generally be no more frequently than every 3 to 5 weeks. Treatment should be continued to maintain IgG trough levels >500 mg/dL.1, 2, 14, 18, 142, 154, 177, 178
Preterm and/or low-birth-weight neonates as prevention for serious infections when severe hypogammaglobulinemia is present 98, 120, 124, 126 Induction and Maintenance: 500-900 mg/kg every 14 days to achieve a trough IgG level of 500-700 mg/dL.14 Administer 400-600 mg/kg every 3 to 4 weeks, titrating the dose based on maintaining trough IgG levels greater than 500 mg/dL.18
Solid organ transplant 24, 119, 128,
129, 130, 135, 136, 137, 141, 145, 147, 148, 149and
Antibody-Mediated Rejection (AMR) (humoral/vascular rejection)138
High-dose IVIG protocol
An in vitro PRA, crossmatch (CMX) test to identify patients most likely to benefit from IVIG therapy.30
For responders on a deceased donor organ waiting list, administer 2 g/kg monthly up to 4 doses. Dose may be repeated at 12 and 24 months. An additional 2 g/kg is given 1 month post-transplant.28, 30
For responders receiving positive CMX living donor organs, administer 1- 4 doses of 2 g/kg monthly with repeat CMX after each dose. An additional 2 g/kg is given 1 month post-transplant.30, 100
The endpoint of therapy is a negative enhanced CDC CMX.

Plasmapheresis/low-dose IVIG protocol30
Plasmapheresis (PP)/low dose IVIG and immunosuppressive agents prior to renal transplantation as follows:
Every other day plasmapheresis (PP) followed by IVIG 100 mg/kg after each PP. In a study by Montgomery et al, a mean of 4 treatments were provided.101

Acute Antibody-Mediated Rejection (AMR) (Humoral/Vascular Rejection)
High-dose IVIG alone (2 g/kg for one dose)23
OR
Plasmapheresis daily or every other day followed by either:
  • IVIG 100 mg/kg for 4-6 doses103, 104, 206, 207 OR
  • IVIG 100-500 mg/kg in divided doses up to a total maximum dose of 2g/kg over a 4 week period 205

IVIG 0.5-2 g/kg total after the final PP treatment103, 206, 207

After the first year post-transplant, IVIG 200 mg/kg every two weeks for three doses. 206

Chronic Active AMR:
One of the following regimens:

  • Plasmapheresis daily or every other day for 4-5 sessions followed by 2 g/kg IVIG (in one or two days), and intravenous rituximab 375 mg/m2, one dose after IVIG. 208
  • intravenous rituximab 375 mg/m2 once on day 1, followed by IVIG 0.4 g/kg once daily for 4 days. 209
  • IVIG 1.5 g/kg, bortezomib (1.3 mg/m2 IV on days 1, 4, 8, and 11), and plasmapheresis (6x). 210

Secondary immunodeficiency with hypogammaglobulinemia as a result of treatment with immunosuppressive agents: 500 mg/kg monthly 99

In patients who have steroid-resistant rejection: IVIG 2-3 g/kg over a period of up to 10 consecutive days.103

INFECTIOUS DISEASE
Toxic shock syndrome Induction: 1 g/kg on day 1, followed by 0.5 g/kg on days 2 and 3. 6, 38, 195 Alternatively, 2 g/kg for one dose and may repeat in 48 hours if the individual remains unstable.36, 38

Maintenance: Maintenance therapy is not warranted.

NEUROLOGICAL AND MUSCULOSKELETAL DISORDERS
Indication
Dosing and Frequency
Acute disseminated encephalomyelitis (ADEM)Induction: 2 g/kg divided over 2-5 days 73, 167, 181

Maintenance: Maintenance therapy is not warranted.
Chronic inflammatory demyelinating polyneuropathies (CIDP)Induction: 2 g/kg divided over 2-5 days. 18, 71, 72, 73, 85, 105, 142, 164
Maintenance: 1 or 2 g/kg divided over 1-5 days and administered every 2-8 weeks. 18, 71, 72, 73, 85, 105, 164
Dermatomyositis and polymyositisInduction and Maintenance:
Adults: 2 g/kg in divided doses administered over 2-5 days and repeated each month for up to 3-6 months. The continued use of IVIG should be based on objective measures of its sustained effectiveness, as seen in improvements in at least one of the following: serum Creatine Kinase (CK) levels, muscle strength, electromyography testing, and/or improvement in rash (for dermatomyositis indication).31, 73, 153, 171

Pediatrics:
1-2 g/kg in divided doses administered over 2 days and repeated each month for up to 3-6 months.32, 73
or 2 g/kg administered every 2 weeks for 3 doses, then each month for a total treatment period of 3-6 months.32, 73, 143

The continued use of IVIG should be based on objective measures of its sustained effectiveness, as seen in improvements in at least one of the following: serum Creatine Kinase (CK) levels, muscle strength, electromyography testing, and/or improvement in rash (for dermatomyositis indication).32, 73
Guillain-Barre syndromeInduction:
Adults: One course of treatment of 400 mg/kg per day for 5 days.14, 53, 56, 59,
61, 66, 67, 68
Pediatrics: 2 g/kg in divided doses administered over 2-5 days 73, 75

Maintenance: There is an absence of peer-reviewed evidence and clinical consensus regarding Maintenance therapy; therefore, dosing is not warranted.
Intractable seizures and epilepsies in infants and childrenInduction and Maintenance: 0.4 g/kg/day for 4-5 consecutive days. The cycle may be repeated every 2-6 weeks.18, 61, 73, 76, 110, 111, 112, 113, 114, 115, 116, 117, 150
Lambert-Eaton myasthenic syndrome Induction: 2 g/kg divided over 2-5 days18, 50, 52, 53, 55, 58, 61, 62, 64, 68, 73, 155, 164, 170

Maintenance: Peer-reviewed literature and lack of clinical consensus for Maintenance is in the investigative state because low level evidence has demonstrated some sporadic clinical benefits.170
Multifocal motor neuropathy (MMN) Induction: 500 mg/kg per day for 5 days.14, 83, 164, 192

Maintenance: 1 to 2 g/kg given over 2 or 5 days administered every 1 to 3 months to sustain improvement.14, 43, 61, 73, 164, 192
Myasthenia gravis syndromeInduction:
Adults: One course of treatment of 400 mg/kg per day for 5 days.33, 50, 51,
53, 54, 57, 60, 61, 63, 65, 68, 69, 73, 142, 179
Neonates, infants, children, adolescents: 2 g/kg in divided doses over 1-5 days. 73, 181

Maintenance: Peer-reviewed literature and lack of clinical consensus for Maintenance is in the investigative state because low-level evidence has demonstrated some sporadic clinical benefits.61, 73, 181

Retreatment: Experience with repeated treatment regimens are not reported at this time.179 Retreatment with 400 mg/kg per day for 5 days may be considered in individuals with a future exacerbation or recurrent worsening of myasthenia gravis syndrome.33, 50, 51, 53, 54, 57, 60, 61, 63, 65, 68, 69
Myasthenic crisisInduction: One course of treatment of 400-600 mg/kg per day for 3 to 5 consecutive days. 14, 50, 53, 55, 61, 68

Maintenance: Maintenance therapy is not warranted.
Neuromyelitis Optica (NMO) (Devic’s Syndrome) 200, 201, 202Induction: 2 g/kg given over 5 days 198, 199
Rasmussen’s encephalitis 142, 169Induction:
Adults: 2 g/kg given over 2 to 5 days. 73
Children: 2 g/kg given over 2 to 5 days. 73

Maintenance: Peer-reviewed literature and lack of clinical consensus for Maintenance is in the investigative state because low level evidence has demonstrated some sporadic clinical benefits.
Relapsing-remitting multiple sclerosis61, 75 Induction: 2 g/kg in divided doses over 5 days.73, 125, 173, 174, 193

Maintenance: There is an absence of peer-reviewed evidence and clinical consensus regarding Maintenance therapy; therefore, dosing is not warranted.173, 174, 175, 179

Retreatment: Retreatment with 2 g/kg in divided doses over 5 days may be considered in individuals with an exacerbation of relapsing-remitting multiple sclerosis. 18, 73, 173, 175
Stiff-Person syndrome 106, 107, 108, 109, 142Induction:
Adults: 2 g/kg over 2-5 days. 61, 73, 132, 146
Children: 2 g/kg over 2 days. 73

Maintenance: IVIG maintenance therapy should be based on a systematic approach to determine the minimum effective dose. Continued use of IVIG should be based on objective measures of its sustained effectiveness. The maximum dose per treatment course should be 2 g/kg.73, 132
Systemic lupus erythematosus (SLE)Induction and Maintenance: 2 g/kg over a 5-day period given monthly.34, 77,
78, 194


DOSING AND FREQUENCY REQUIREMENTS FOR SUBCUTANEOUS IMMUNE GLOBULIN (SCIG)

Examples of SCIG therapy include Cutaquig, Cuvitru, Hizentra®, HyQvia and Xembify. Examples of IVIG products that may be administered via subcutaneous infusion for PIDD include Gammagard Liquid®, Gammaked®, Gamunex-C®.

Indication
Dosing and Frequency
Immunodeficiency Syndromes:
Hyperimmunoglobulinemia E syndrome (HIES)
and
Primary immunodeficiency disorders (PIDD) 154
Induction: 100-200 mg/kg weekly 176, 178, 196

SCIG products administered via subcutaneous infusion

Cutaquig 187:
Individuals previously on IVIG treatment should delay Cutaquig administration approximately 1 week after the last infusion of their previous treatment.

    When switching to Cutaquig from IVIG at regular intervals for at least 3 months:
    Weekly dosing:
    Initial dose = 1.4 x previous IVIG (in grams)/number of weeks between IVIG doses.

    More frequent dosing: Provided the total weekly dose is maintained, any dosing interval from daily up to weekly can be used.

    Monitor serum trough IgG trough levels to guide subsequent dose adjustments and dosing intervals as needed. See prescribing information for more information.

    The target serum IgG trough levels are approximately 23% higher than the last IVIG trough level.

Individuals previously on SCIG treatment:
    When switching to Cutaquig from SCIG at regular intervals for at least 3 months: The weekly dose of Cutaquig is the same as other SCIG.

    Monitor serum trough IgG trough levels to guide subsequent dose adjustments and dosing intervals as needed. See prescribing information for more information.

Cuvitru9:
Individuals previously on IVIG or HyQvia (SCIG) treatment should delay Cuvitru administration approximately 1 week after the last infusion of their previous treatment.
    Weekly dosing:
    Initial dose = 1.3 x previous IVIG or HyQvia (SCIG) dose (in grams)/number of weeks between IVIG or HyQvia (SCIG) doses.

    Bi-weekly dosing (every 2 weeks):
    Initial dose = Multiply the calculated weekly dose by two.

    Frequent dosing (2 to 7 times per week):
    Initial dose = Divide the calculated weekly dose by the desired number of times per week.

    Individuals switching from SCIG other than HyQvia:
    The weekly dose of Cuvitru is the same as other SCIG.
    See Bi-weekly and Frequent dosing (above) for more information.

    Monitor serum trough IgG trough levels to guide subsequent dose adjustments and dosing intervals as needed. See prescribing information for more information9.

Hizentra®39: The initial weekly dose of Hizentra® is calculated to achieve a systemic serum IgG exposure (area under concentration-time curve [AUC]) not inferior to that of the previous IVIG treatment.
    Weekly dosing:
    Initial dose = 1.37 x previous IVIG dose (in grams)/number of weeks between IVIG doses.

    Bi-weekly dosing (every 2 weeks):
    Initial dose = Multiply the calculated weekly dose by two.

    Frequent dosing (2 to 7 times per week):
    Initial dose = Divide the calculated weekly dose by the desired number of times per week.

    Adjust the dose over time based on clinical response and serum IgG trough levels. Measure the IgG trough levels after 2 to 3 months of treatment with Hizentra®.
    When switching from IVIG to:
    • Weekly Hizentra® dosing: The target serum IgG trough levels are approximately 16% higher than the last IVIG trough level.
    • Biweekly Hizentra® dosing: The target serum IgG trough levels are approximately 10% higher than the last IVIG trough level.

    When switching from weekly to biweekly Hizentra® dosing: The target serum IgG trough levels are approximately 5% lower than the last IVIG trough level.

    When switching from weekly to more frequent Hizentra® dosing (2 to 7 times per week): The target serum IgG trough levels are approximately 3-4% higher than the last IVIG trough level.39

HyQvia10:
    Titrate dose and frequency from once-weekly dosing to once-every 3-4 weeks, as follows:
    Week 1: 1st infusion (weekly dosing) at 25% of targeted dose
    Week 2: 2nd infusion (every 2-week dosing) at 50% of targeted dose
    Week 3: No infusion
    Week 4: 3rd infusion (every 3-week dosing) at 75% of targeted dose
    Week 5: No infusion
    Week 6: No infusion
    Week 7: 4th infusion (every 4-week dosing) at 100% of targeted dose (if required)

    Individuals naïve to IgG treatment or switching from other SCIG: After initial titration, administer HyQvia at 300 to 600mg/kg at 3-4 week intervals.

    Individuals previously on another IgG treatment should delay HyQvia administration approximately 1 week after the last infusion of their previous treatment.

    Individuals switching from IVIG: After initial titration, administer HyQvia at same dose and frequency as the previous IV treatment.

    Adjust dose by measuring serum trough IgG trough levels and calculating difference from baseline IVIG trough levels, then refer to dosage adjustment tables listed within prescribing information for particular product.10

Xembify211:
    Individuals previously on IVIG treatment should delay Xembify administration approximately 1 week after the last infusion of their previous treatment.

    Weekly dosing:
    Initial dose = 1.37 x previous IVIG dose (in grams)/number of weeks between IVIG doses.

    Frequent dosing (2 to 7 times per week):
    Initial dose = Divide the calculated weekly dose by the desired number of times per week.

    Individuals switching from another SCIG:
    The weekly dose of Xembify is the same as other SCIG.

    Adjust the dose over time based on clinical response and serum IgG trough levels. Measure the IgG trough levels after 2 to 3 months of treatment with Xembify.211

IVIG products that may be administered via subcutaneous infusion

Gammagard Liquid®83:
    Initial dose = 1.37 x previous IVIG dose/number of weeks between IVIG doses.

    Maintenance dose is based on clinical response and target IgG trough level.

Gammaked®, Gamunex-C®:
    The initial weekly dose is calculated to achieve a systemic serum IgG exposure (area under concentration-time curve [AUC]) not inferior to that of the previous IVIG treatment.

    Initial dose = 1.37 x previous IVIG dose (in grams)/number of weeks between IVIG doses.

    Adjust the dose over time based on clinical response and serum IgG trough levels. Measure the IgG trough levels after two to three months of treatment with this drug. 84, 85
Neurological and Musculoskeletal Disorders
Chronic inflammatory demyelinating polyneuropathies (CIDP)
Hizentra®39:
    Initiate therapy 1 week after the last IGIV infusion.

    Weekly dosing:
    The recommended subcutaneous dose is 0.2 g/kg (1 mL/kg) per week, administered in 1 or 2 sessions over 1 or 2 consecutive days.
    • Individuals switching from IVIG: In the clinical study, a dose of 0.4 g/kg (2 mL/kg) per week was used.

    If CIDP symptoms worsen, consider re-initiating treatment with an IVIG product approved for the treatment of CIDP, while discontinuing Hizentra®.
    • If improvement and stabilization are observed during IVIG treatment, consider reinitiating Hizentra® at 0.4 g/kg/week, administered in 2 sessions/week over 1 or 2 consecutive days, while discontinuing IVIG.
    • If CIDP symptoms worsen, consider re-initiating treatment with an IVIG product approved for the treatment of CIDP, while discontinuing Hizentra®.

    Monitor clinical response and adjust the duration of therapy. Maintenance therapy has been studied for 18 months; therapy beyond this period should be individualized based upon the individual's response and need for continued therapy.


References

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and
US Food and Drug Administration (FDA). Vaccines, Blood & Biologics. Immune globulin intravenous (IGIV) indications. 03/08/2018. [FDA Web site]. Available at:
http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm133691.htm . Accessed February 11, 2019.

2. Yong PL, Boyle J, Ballow M, et al. Use of intravenous immunoglobulin and adjunctive therapies in the treatment of primary immunodeficiencies: A working group report of and study by the Primary Immunodeficiency Committee of the American Academy of Allergy Asthma and Immunology. Clin Immunol. 2010 135;255-263.

3. Ahmed AR, Dahl MV. Consensus statement on the use of intravenous immunoglobulin therapy in the treatment of autoimmune mucocutaneous blistering diseases. Arch Dermatol. 2003;139:1051-1058.

4. Korman NJ. Macular, papular, vesiculobullous, and pustular diseases. In: Goldman L, Schafer A eds. Goldman's Cecil Medicine, 24th ed.

5. Morelli JG. Vesiculobullous disorders. In: Kliegman RM, Stanton BF, St. Geme III JW, Schor NF, Behrman RE eds. Nelson Textbook of Pediatrics, 19th ed.

6. Rey J B, Luria RB. Treatment of scleromyxedema and the dermatoneuro syndrome with intravenous immunoglobulin. J Am Acad Dermatol. 2009;60:1037-1041.

7. Sroa N, Campbell S, Bechtel M. Intravenous immunoglobulin therapy for scleromyxedema: a case report and review of the literature. J Drugs Dermatol. 2010;9:263-265.

8. Jolles S, Hughes J. Use of IVIG in the treatment of atopic dermatitis, urticaria, scleromyxedema, pyoderma gangrenosum, psoriasis and pretibial myxedema. Int Immunopharmacol. 2006;6:579-591.

9. Cuvitru, Immune Globulin Subcutaneous (Human), 20% Solution approval and prescribing information. Baxalta US Inc.: Lexington, MA. 07/2018. Available at: https://www.cuvitru.com/ . Accessed February 11, 2019.

10. HyQvia. package insert. Baxalta US Inc.: Lexington, MA. 01/2019. Available at: http://www.hyqvia.com/ . Accessed February 11, 2019.

11. Mir MA. Immune thrombocytopenia and pregnancy: Treatment & management and medication. Updated 10/09/2015. Available at: http://emedicine.medscape.com/article/208697-treatment and
http://emedicine.medscape.com/article/208697-medication#showall. Accessed March 7, 2019.

12. Anderson D, Kaiser A, Blanchette V, et al. Guidelines on the use of intravenous immune globulin for hematologic conditions. Transfus Med Rev. 2007;21:S9-S56.

13. Greaves M. Guidelines on the investigation and management of thrombocytopenia in pregnancy and neonatal alloimmune thrombocytopenia. Br J Haematol1996;95(1).

14. Darabi K, Abdel-Wahab O Dzik WH. Current usage of intravenous immune globulin and the rationale behind it: the Massachusetts General Hospital data and a review of the literature. Transfusion. 2006;46:741-753.

15. Sapir T, Blank M, Shoenfeld Y. Immunomodulatory effects of intravenous immunoglobulins as a treatment for autoimmune diseases, cancer, and recurrent pregnancy loss. Ann NY Acad Sci. 2005;1051:743-778.

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Version Effective Date: 10/21/2019
Version Issued Date: 10/21/2019
Version Reissued Date: N/A

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