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


NATL


[Immunoglobulin for Aneurysm in Kawasaki Syndrome]

These criteria apply to requests for use of immunoglobulins for the indication of Aneurysm in Kawasaki Syndrome 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 (including Bivigam, Carimune NF, Flebogamma, Gamunex-C, Gammaked, Gammagard Liquid, Gammagard S/D, Gammaplex, Octagam, Privigen, 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 Kawasaki syndrome or Incomplete (Atypical) Kawasaki Disease confirmed by a Cardiologist, Allergist or Rheumatologist
    OR
    • Meeting American Heart Association (AHA) diagnostic criteria when all the following are met:
    1. Fever persisting at least 5 days
      • The fever typically is high spiking and remittent, with peak temperatures generally >39oC (102oF) and in many cases >40oC (104oF)
    AND
    2. Presence of at least 4 principal features:
      • Changes in extremities
        • Acute: Erythema of palms, soles; edema of hands, feet
        • Subacute: Periungual peeling of fingers, toes in weeks 2 and 3
      • Polymorphous exanthema
      • Bilateral bulbar conjunctival injection without exudates
      • Changes in lips and oral cavity: Erythema, lips cracking, strawberry tongue, diffuse injection of oral and pharyngeal mucosae
      • Cervical lymphadenopathy (>1.5 cm diameter), usually unilateral
    OR
    Presence of <4 principal features and coronary artery disease detected by 2D echocardiography (2DE) or coronary angiography
      • Echocardiogram is positive if any of these 3 conditions are met:
        • z score of left anterior descending (LAD) or right coronary artery (RCA) ≥2.5
        • Coronary arteries meet Japanese Ministry of Health criteria for aneurysms
        • ≥3 other suggestive features exist:
          • Perivascular brightness
          • Lack of tapering
          • Decreased left ventricle function
          • Mitral regurgitation
          • Pericardial effusion
          • z scores in LAD or RCA of 2-2.5
    AND
    3. Exclusion of other diseases with similar findings
      • Viral infections (i.e., measles, adenovirus, enterovirus, Epstein-Barr virus)
      • Scarlet fever
      • Staphylococcal scalded skin syndrome
      • Toxic shock syndrome
      • Bacterial cervical lymphadenitis
      • Drug hypersensitivity reactions
      • Stevens-Johnson syndrome
      • Juvenile rheumatoid arthritis
      • Rocky Mountain spotted fever
      • Leptospirosis
      • Mercury hypersensitivity reaction (acrodynia)
  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: Immune Globulin Conditions Not Medically Necessary - NATL.
  4. General Information:
    • Kawasaki disease, the leading cause of acquired heart disease in children in the United States is an acute self-limited vasculitis of childhood. Coronary artery aneurysms or ectasia develop in 15% to 25% of untreated children and may lead to ischemic heart disease or sudden death.
    • Treatment of Kawasaki disease in the acute phase is directed at reducing inflammation in the coronary artery wall and preventing coronary thrombosis, whereas long-term therapy is aimed at preventing myocardial ischemia or infarction.
    • The efficacy of intravenous immunoglobulin (IVIG) administered in the acute phase of Kawasaki disease in reducing the prevalence of coronary artery abnormalities is well-established. The mechanism of action of IVIG in treating Kawasaki disease is unknown; however IVIG appears to have a generalized anti-inflammatory effect.
    • IVIG together with aspirin should be instituted within the first 10 days of illness (within 7 days if possible). IVIG also should be administered after the 10th day of illness (i.e., children in whom the diagnosis was missed earlier) if they have either persistent fever without other explanation or aneurysms and ongoing systemic inflammation, as manifested by elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP).
    • For patients with persistent or recurrent fever after initial IVIG infusion, IVIG retreatment may be useful. Failure to respond usually is defined as persistent or recrudescent fever ≥36 hours after completion of the initial IVIG infusion. Most experts recommend retreatment with IVIG, 2 g/kg. The putative dose-response effect of IVIG forms the theoretical basis for this approach
  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)

    2 g/kg IV as single infusion within 10 days (preferably 7 days) of fever onset.
    Gammagard S/D: 1 g/kg single IV dose or 400 mg/kg IV QD for four consecutive days beginning within seven days of fever onset.

    Administer concomitantly with aspirin (80-100 mg/kg/day in four divided doses)
    Initial authorization:
    single infusion during acute phase

    Retreatment may be considered contingent upon receipt of chart notes
    (see general information about retreatment)
  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 vials
    Flebogamma: 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 Liquid: 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: 0.5 g, 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 bottles; 10% (1 g/10 mL) in 20 mL, 50 mL, 100 mL, 200 mL bottles
    Privigen: 10% (100 mg/mL) in 50 mL, 100 mL, 200 mL, 400 mL vials
    Subcutaneous Immunoglobulin
    Gammagard Liquid: 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) IgG 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. Bivigam [Prescribing Information] Boca Raton, FL; Biotest Pharmaceuticals: April 2014.
    2. Carimune Nonfiltered [Prescribing Information] Bern, Switzerland: CSL Behring AG; October 2013.
    3. Flebogamma 5% DIF [Prescribing Information] Barcelona, Spain: Instituto Grifols, S.A.; August 2014.
    4. Flebogamma 10% DIF [Prescribing Information] Barcelona, Spain: Instituto Grifols, S.A.; July 2014.
    5. Gammagard Liquid [Prescribing Information] Westlake Village, CA; Baxter Healthcare Corporation; September 2013.
    6. Gammagard S/D [Prescribing Information] Westlake Village, CA: Baxter Healthcare Corporation; September 2013.
    7. Gammaked [Prescribing Information] Research Triangle Park, NC: Grifols Therapeutic Inc.; September 2013.
    8. Gammaplex [Prescribing Information] Hertfordshire, United Kingdom: Bio Products Laboratory Limited; June 2014.
    9. Gamunex-C [Prescribing Information] Research Triangle Park, NC: Grifols Therapeutics Inc.; July 2014.
    10. Octagam 5% [Prescribing Information] Hoboken, NJ: Octapharma USA Inc.; November 2013.
    11. Octagam 10% [Prescribing Information] Vienna, Austria: Octapharma Pharmazeutika Produktionsges m.b.H; December 2014.
    12. Hizentra [Prescribing Information] Bern, Switzerland: CSL Behring AG; February 2015.
    13. HyQvia [Prescribing Information] Westlake Village, CA: Baxter Healthcare Corporation; September 2014.
    14. Privigen [Prescribing Information] Bern, Switzerland: CSL Behring AG; December 2013.
    15. Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, Shulman ST, Bolger AF, Ferrieri P, Baltimore RS, Wilson WR, Baddour LM, Levison ME, Pallasch TJ, Falace DA, Taubert KA. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 2004;110:27472771.
    16. Centers for Disease Control and Prevention Kawasaki Syndrome Case Definition: http://www.cdc.gov/kawasaki/.
    17. MicromedexR Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed July 2, 2015.
    18. Immune Globulin. American Hospital Formulary Service Drug Information. Avalable at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed July 2, 2015.
    19. Clinical Pharmacology Web site. Available at http://www.clinicalpharmacology-ip.com/default.aspx. Accessed July 2, 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: 10-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, 14-JUL-14 DT, 23-FEB-15 DM, 04-JUN-15 PT