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Prior Authorization Protocol
BIVIGAMTM, CARIMUNE NFR, FLEBOGAMMA DIFR, GAMMAGARD LIQUIDR, GAMMAGARD S/DR, GAMMAKEDR, GAMMAPLEXTM, GAMUNEX-CR,OCTAGAMR, PRIVIGENR, HIZENTRATM, HYQVIA

NATL

[Immunoglobulin for Neonatal Alloimmune Thrombocytopenia]

These criteria apply to requests for use of immunoglobulins for the indication of Neonatal Alloimmune Thrombocytopenia only. For the use of immunoglobulins for any other indication, please refer to the appropriate indication specific criteria.
Coverage of drugs is first determined by the member’s pharmacy or medical benefit. Please consult with or refer to the Evidence of Coverage document.
  1. FDA Approved Indications:
    • For immune globulin intravenous (IVIG) (including Gamunex-C, Gammaked and Gammagard when used intravenously)
      • Replacement therapy for primary immunodeficiency (PI) This includes, but is not limited to, congenital agammaglobulinemia, common variable immunodeficiency, X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.
      • Treatment of patients with idiopathic thrombocytopenic purpura (ITP) to raise platelet counts to prevent bleeding or to allow a patient with ITP to undergo surgery.
      • Maintenance therapy to improve muscle strength and disability in adult patients with Multifocal Motor Neuropathy (MMN).
      • Prevention of bacterial infections in patients with hypogammaglobulinemia and/or recurrent bacterial infections associated with B-cell chronic lymphocytic leukemia (CLL).
      • Prevention of coronary artery aneurysms associated with Kawasaki syndrome.
      • Treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) to improve neuromuscular disability and impairment and for maintenance therapy to prevent relapse.
    • For immune globulin subcutaneous (including Gamunex-C, Gammaked, Gammagard Liquid, Hizentra, and Hyqvia when used subcutaneously)
      • Treatment of/replacement therapy for patients with primary immunodeficiency (PI). This includes, but is not limited to, congenital agammaglobulinemia, common variable immunodeficiency (CVID), X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.
  2. Health Net Approved Indications and Usage Guidelines:
    • Diagnosis of neonatal alloimmune thrombocytopenia (NAIT) or fetal alloimmune thrombocytopenia (FAIT)
    AND
      • Previous pregnancy affected by FAIT and father homozygous for HPA-1a
    OR
      • At 20 weeks cordocentesis reveals fetal platelets < 100 x 109/L
    OR
      • Symptomatic neonates with severe thrombocytopenia, who are at high risk of developing intracranial hemorrhage when washed irradiated maternal platelets are not available, have not been successful, have become intolerable, or are contraindicated.
  3. Coverage is Not Authorized For:
    • Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.
    • A list of specific indications for which coverage is not authorized may be found in the PA guideline: Immunoglobulin Conditions Not Medically Necessary - NATL.
  4. General Information:
    • NAIT is caused by maternal alloantibodies directed against fetal (paternally inherited) platelet antigens as a result of feto-maternal transplacental passage of incompatible platelets during pregnancy.
    • HPA-1a is the platelet-specific antigen implicated in most cases of neonatal alloimmune thrombocytopenia.
    • Administering IVIG to the mother during pregnancy is the most successful strategy for increasing the fetal platelet count and has become the recommended standard treatment of known fetal alloimmune thrombocytopenia.
    • Studies have shown that weekly infusions (1 g/kg maternal body weight) beginning at 20 to 24 weeks' gestation stabilize or increase the fetal platelet count in fetuses with documented alloimmune thrombocytopenia.
    • In very high-risk pregnancies (intracranial hemorrhage in a previous sibling before 30 weeks' gestation), some investigators recommend starting IVIG therapy as early as 12 to 14 weeks' gestation.
    • Although the mechanism of action of IVIG in FAIT is not clearly defined, it is postulated that IVIG decreases maternal alloantibodies and may also block transplacental transport of maternal antiplatelet antibodies.
    • There is still no consensus on the optimal protocol for managing IVIG after it is begun
  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose
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    * Requires Prior Authorization
  6. Recommended Dosing Regimen and Authorization Limit:
    Drug Dosing Regimen Authorization Limit

    IVIG (Various Brand names)

    Weekly infusions of 1 to 2 g/kg maternal body weight per week beginning at 20 to 24 weeks

    Very high-risk pregnancies:
    IVIG therapy may be started as early as 12 to 14 weeks gestation
    6 months or to member's renewal period, whichever is longer
  7. Product Availability:
    Intravenous Immunoglobulin
    Bivigam: 10% (1 g/10 mL) in 50 mL, 100 mL vials
    Carimune NF powder for injection: 3 g, 6 g, 12 g bottles
    Flebogamma DIF: 5% (50 mg/mL) in 10 mL, 50 mL, 100 mL, 200 mL, 400 mL vials; 10% (5 g/50 mL) in 50 mL, 100 mL, 200 mL vials
    Gammagard: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL, 300 mL vials
    Gammagard S/D powder for injection: 2.5 g, 5 g, 10 g bottles
    Gammaked: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL vials
    Gammaplex: 5% (50 mg/mL) in 50 mL, 100 mL, 200 mL, 400 mL vials
    Gamunex-C: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL vials
    Octagam: 5% (50 mg/mL) in 20 mL, 50 mL, 100 mL, 200 mL, 500 mL
    Octagam: 10% (50 mg/mL) in 20 mL, 50 mL, 100 mL, 200 mL
    Privigen: 10% (100 mg/mL) in 50 mL, 100 mL, 200 mL, 400 mL vials
    Subcutaneous Immunoglobulin
    Gammagard: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL, 300 mL vials
    Gammaked: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL vials
    Gamunex-C: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL vials
    Hizentra protein solution for subcutaneous injection: 20% (0.2 g/mL) in 5 mL, 10 mL, 20 mL, 50 mL vials
    HyQvia: 10% (1 g/10 mL) in 25 mL, 50 mL, 100 mL, 200 mL, 300 mL vials and 160 U/mL recombinant human hyaluronidase in 1.25 mL, 2.5 mL, 5 mL, 10 mL, 15 mL vials
  8. References:
    1. MicromedexR Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed June 19, 2015.
    2. Immune Globulin. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 19, 2015.
    3. Gammagard-SD [Prescribing Information], Westlake Village, CA; Baxter: September 2013.
    4. Gammaplex [Prescribing Information], Hertfordshire, UK; Bio Products Laboratory Ltd: February 2014.
    5. Gamunex-C [Prescribing Information]. Research Triangle Park, NC. Grifols: July 2014.
    6. Hizentra [Prescribing Information], Bern, Switzerland: CSL Behring AG; January 2015.
    7. Carimune NF [Prescribing Information], CSL Behring AG, September 2013.
    8. Privigen [Prescribing Information], CSL Behring AG, November 2013.
    9. Gammagard Liquid [Prescribing Information], Westlake Village, CA; Baxter: September 2013.
    10. American College of Obstetricians and Gynecologists (ACOG). Management of early pregnancy loss. ACOG Bulletin #24. 2001, Feb 12.
    11. American College of Obstetricians and Gynecologists: Thrombocytopenia in pregnancy. ACOG practice bulletin, Number 6, September 1999. Clinical management guidelines for obstetrician- gynecologists. Int J Gynaecol Obstet 1999 Nov; 67(2): 117-28.
    12. Fernandes CJ. Neonatal Thrombocytopenia. UpToDate.Accessed July 7, 2014. Available at: http://www.uptodate.com/contents/neonatal-thrombocytopenia?source=search_result&search=IVIG+for+neonaltal+alloimmune+thrombocytopenia&selectedTitle=1%7E150
    13. Giers G, Wenzel F, Fischer J, et al. Retrospective comparison of maternal vs. HPA-matched donor platelets for treatment of fetal alloimmune thrombocytopenia. Vox Sang. 2010 Apr;98(3 Pt 2):423-30. Epub 2009 Oct 27.
    14. Paidas MJ. Prenatal management of neonatal alloimmune thrombocytopenia. UpToDate. June 2015.
    15. Flebogamma [Prescribing Information], Los Angeles, CA; Grifols Biologicals: September 2013.
    16. Gammaked [Prescribing Information], Fort Lee, NJ; Kedrion Biopharma: September 2013.
    17. Octagam 5% [Prescribing Information]. Hoboken, NJ; Octapharma USA: October 2013.
    18. Bivigam [Prescribing Information], Boca Raton, FL; Biotest Pharmaceuticals: October 2013.
    19. Octagam 10% [Prescribing Information]. Hoboken, NJ; Octapharma USA: December 2014.
    20. HyQvia [Prescribing Information]. Westlake Village, CA; Baxter: September 2014.
The material provided to you are guidelines used by this plan to authorize, modify or determine coverage for persons with similar illnesses or conditions. Specific care and treatment may vary depending on individual need and the benefits covered under your contract.
Draft Prepared: 05-DEC-12 MJM
Approved By Health Net National P&T: 20-FEB-13, 20-NOV-13, 19-NOV-14, 18-NOV-15
Revised: 15-JUN-13 SR, 07-JUL-14 MH, 23-FEB-15 DM, 19-JUN-15 EA