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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 Pemphigus Vulgaris]

These criteria apply to requests for use of immunoglobulins for the indication of Pemphigus Vulgaris 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 Pemphigus Vulgaris, Pemphigus Foliaceus, Bullous Pemphigoid, Mucous Membrane Pemphigoid (a.k.a. Cicatricial Pemphigoid), or Epidermolysis Bullosa Acquisita
    AND
    • The diagnosis has been proven by biopsy and confirmed by pathology report
    AND
    • The condition is rapidly progressing, extensive or debilitating
    AND
    • Failure or clinically significant adverse effects to corticosteroids and immunosuppressive agents (e.g., cyclophosphamide, azathioprine, mycophenolate mofetil).
  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:
    • IVIG therapy for Pemphigus Vulgaris must be used only for short-term therapy and not as a maintenance therapy.
    • IVIG dose adjustments:
      • Adjustment of the IVIG dose and time interval between doses should be based on trough levels measured every month for the first three months of therapy and again at six months
      • Adjustments to infusion rates and measuring of serum IgG levels may be needed during infections or in persons who have a high catabolism of infused IgG
      • To reduce infection frequency in immunodeficient patients, serum trough levels should be maintained at 670-730 mg/dl, a value close to the lower limit of normal. All IgG trough levels outside of the low normal range of 6.7-7.3 mg/dl require dosage adjustment.
    • The treatment is considered complete when the patient is free of disease after a 16-week interval between the last two infusion cycles.
    • Examples of clinically significant adverse effects to corticosteroids, immunosuppressive agents (e,g., cyclophosphamide, azathioprine, mycophenolate mofetil) are diabetes or fractures from chronic steroid use.
    • Black Box Warning: Thrombosis, renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur.
  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose

    systemic glucocorticoid (Various - prednisone, prednisolone, or methylprednisolone)

    Up to a maximum of an equivalent of 1.5 to 2 mg/kg per day of prednisone

    2 mg/kg/day

    cyclophosphamide (CytoxanR)

    Pulsed regimen of monthly infusion of dexamethasone 100 mg IV QD for 3 days and cyclophosphamide
    monthly infusion of 500 mg IV QD for 1 day plus cyclophosphamide 50 mg PO QD in between pulsed therapy
    OR
    cyclophosphamide 2 to 2.5 mg/kg of ideal body weight PO QD and prednisone 1 mg/kg
    of ideal body weight PO QD followed by a taper after two to three months

    This field intentionally left blank

    azathioprine (ImuranR)

    Dosing of azathioprine is influenced by the level of activity thiopurine methyltransferase (TPMT) enzyme
    High TPMT activity:
    up to 2.5 mg/kg of ideal body weight PO QD
    Intermediate or low TPMT activity:
    up to 0.5 to 1.5 mg/kg PO QD
    Absent TPMT activity:
    should not be treated with azathioprine

    2.5 mg/kg/day

    mycophenolate mofetil (CellceptR)

    2 g PO QD (taken as 1 g PO BID) added to systemic glucocorticoid therapy.
    Enteric-coated can be given as 720 mg PO BID

    3 g/day

    * Requires Prior Authorization
  6. Recommended Dosing Regimen and Authorization Limit:
    Drug Dosing Regimen Authorization Limit
    (IVIG) Bivigam, Gammaplex Flebogamma, Gammagard, Gammagard S/D, Gammaked, Gamunex-C, Octagam,
    Cariumune NF, Privigen
    2 gm/kg at four-week intervals until lesions are healed.
    Frequency of infusions can take place at intervals of 6, 8, 10, 12, 14, and 16 weeks.

    Other protocols that will be considered acceptable:
    400 mg/kg/day for 5 days, 1 cycle only (may repeat up to three times in a 6-month period) OR
    300 mg/kg/day for 5 days at monthly intervals (3 cycles)

    6 months or to member's renewal period, whichever is longer.

    The treatment is considered complete when the patient is free of
    disease after a 16-week interval between the last two infusion cycles

  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, 400 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, 400 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 03, 2015.
    2. Immune Globulin. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 03, 2015.
    3. Gammagard-SD [Prescribing Information], Westlake Village, CA; Baxter: September 2013.
    4. Gammaplex [Prescribing Information], Bio Products Laboratory Ltd. September 2013.
    5. Gamunex-C [Prescribing Information]. Research Triangle Park, NC. Grifolis Therapeutics Inc.: July 2014.
    6. Hizentra [Prescribing Information], Bern, Switzerland; CSL Behring AG, January 2015.
    7. Carimune [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. Ahmed A. IVIG therapy in the treatment of patients with bullous pemphigus unresponsive to conventional immunosuppressive treatment. J Am Acad. Derm. 2001;45:1.
    11. Bystryn JC, Jiao D, Natow S. Treatment of pemphigus with intravenous immunoglobulin. J Am Acad Dermatol. 2002;47(3):358-63.
    12. Sami N, Qureshi A, Ruocco E, Ahmed AR. Corticosteroid-sparing effect of intravenous immunoglobulin therapy in patients with pemphigus vulgaris. Arch Dermatol. 2002;138(9):1158-62.
    13. Harman KE, Albert S, Black MM. Guidelines for the management of pemphigus vulgaris. Br J Dermatol 2003 Nov;149(5):926-37. Available at: http://www.guideline.gov/summary/summary.aspx?doc_id=6617&nbr=004161&string=IVIG+AND+Pemphigus+AND+Vulgaris
    14. Goldstein BG, Goldstein AO. Pemphigus. UpToDate. December 2, 2011. Available at: http://www.uptodate.com/contents/pemphigus?source=search_result&search=IVIG+for+pemphigus+vulgaris&selectedTitle=1%7E150
    15. Hertl M, Geller S. Initial management of pemphigus vulgaris and pemphigus foliaceus. UpToDate. June 2013.Ishii N, Hashimoto T, Zillikens D, et al. High-dose intravenous immunoglobulin (IVIG) therapy in autoimmune skin blistering diseases. Clin Rev Allergy Immunol 2010; 38:186.
    16. Flebogamma [Prescribing Information], Los Angeles, CA; Grifols Biologicals: September 2013.
    17. Gammaked [Prescribing Information], Fort Lee, NJ; Kedrion Biopharma: September 2013.
    18. Octagam 5% [Prescribing Information]. Hoboken, NJ; Octapharma USA: October 2013.
    19. Bivigam [Prescribing Information], Boca Raton, FL; Biotest Pharmaceuticals: October 2013.
    20. Octagam 10% [Prescribing Information]. Hoboken, NJ; Octapharma USA: July 2014.
    21. HyQvia [Prescribing Information]. Westlake Village, CA; Baxter: September 2014.
    22. Clinical Pharmacology Web site. Available at: http://cpip.gsm.com/. Accessed June 04, 2015
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 JB
Approved By Health Net National P&T: 20-FEB-13, 20-NOV-13, 19-NOV-14, 18-NOV-15
Revised: 15-JUN-13 SR, 11-JUL-14 MH, 23-FEB-15 DM, 04-JUN-15 HG