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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 Paraneoplastic Disorders]


These criteria apply to requests for use of immunoglobulins for the indication of Paraneoplastic Disorders 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 paraneoplastic neurological syndrome opsoclonus-myoclonus-syndrome
    AND
    • Failure of or clinically significant adverse effects to adrenocorticotropic hormone (ACTH) and corticosteroids

    OR

    • Diagnosis of paraneoplastic neurological syndrome anti-NMDA encephalitis, (anti-N-methyl D-aspartate receptor encephalitis)
  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
    • Paraneoplastic cerebellar degeneration
    • Opsoclonus-myoclonus syndrome (OMS) with anti-Yo Ab (also known as APCA)
    • Paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) with anti-Hu Ab (also known as ANNA-1)
    • Paraneoplastic encephalomyelitis
    • Paraneoplastic sensory neuropathy or polyneuropathy
  4. General Information:
    • Paraneoplastic syndromes are the remote effects of a cancer unrelated to the effects of the tumor or its metastasis. Sometimes they are associated with low immune globulin values and sometimes they are associated with autoantibodies.
    • The combination of IVIG, cyclophosphamide, and methylprednisolone in patients with paraneoplastic cerebellar degeneration and antineuronal antibodies in not effective.
    • Anti-NMDA encephalitis
      • Although no standard of care for anti-NMDA encephalitis exists, on the basis of data from the reviews completed, concurrent IVIG (0.4 g/kg per day for 5 days) and methylprednisolone (1 g/day for 5 days) is preferred over plasma exchange.
      • If no response is seen after 10 days, a second-line therapy is started.
      • Although there is a paucity of randomized controlled and comparative trials regarding the use of IVIG for this disorder, because of the severity of anti-NMDA encephalitis and on the basis of data from the completed reviews and case series, it has been noted that individuals who received early tumor treatment (usually with immunotherapy) had better outcome and fewer neurological relapses than the rest of the patients,
      • IVIG given concurrently with corticosteroids has been determined to assist with full or substantial recovery in approximately 75% of the individuals with anti-NMDA encephalitis.
    • Opsoclonus-myoclonus-syndrome or "dancing eyes-dancing feet" syndrome is a rare neurological disorder that affects infants and young children and has been described in adult patients with cancer
      • The current therapeutic strategies for OMS provide a broad spectrum of nonselective immunotherapies, including noncytotoxic and cytotoxic drugs, intravenous immunoglobulins, ACTH and plasma exchange
      • Intravenous immunoglobulin G is occasionally used as an alternative to ACTH.
      • Altogether, the available evidence suggests that IVIG may be an effective treatment in parainfectious and idiopathic OMS.
      • Treatment with IVIG has been reported in a few idiopathic adult-onset OMS cases in literature and they have concluded that idiopathic OMS presents an age dependent prognosis and immunotherapy. IVIG seems to be associated with a faster recovery.
      • Trends in the standard of care of OMS report that ACTH, prednisone, and intravenous immunoglobulin were used with equal frequency, but ACTH was associated with the best early response
  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose

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

    An equivalent of prednisone 2 mg/kg per day with a prolonged taper over several months and pulsed dexamethasone therapy of 20 mg/m2 for three days, given monthly

    This field intentionally left blank.

    H.P. ActharR Gel (repository corticotropin)*

    Begin with 75 U/m2 IM/SC BID for one week and subsequent tapers based upon clinical response for a total therapy period of 40 weeks,

    This field intentionally left blank.
    * Requires Prior Authorization
  6. Recommended Dosing Regimen and Authorization Limit:
    Drug Dosing Regimen Authorization Limit

    IVIG (Various Brand names)

    anti-NMDA encephalitis
    0.4 g/kg per day for 5 days (with methylprednisolone 1 g/day for 5 days)
    OMS
    1-2 g/kg over 6 hours every month

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

    (IGSC) Gammaked, Gamunex-C, Gammagard

    100 to 200 mg/kg body weight SC per week
    OR
    Initial weekly subcutaneous dose can be calculated by multiplying the previous IVIG dose by 1.37,
    and then dividing this dose into weekly doses based on the patient's previous IVIG treatment interval.

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

    (IGSC) Hizentra

    Administer SC at regular intervals from daily up to every two weeks (biweekly).
    To calculate the initial weekly dose of Hizentra, multiply the previous IVIG dose in grams by the dose adjustment factor of 1.37; then divide this by the number of weeks between doses during the patient`s IVIG treatment (i.e., 3 or 4).
    Weekly Dosing: Administer calculated weekly dose starting 1 week after the last IVIG infusion
    Biweekly Dosing: Administer twice the calculated weekly dose starting 1 or 2 weeks after the last IVIG infusion or 1 week after the last IGSC infusion.
    Frequent Dosing (2 to 7 times per week): Divide the calculated weekly dose by the desired number of times per week. Start Hizentra 1 week after the last IVIG or IGSC infusion.
    To convert the Hizentra dose (in grams) to milliliters (mL), multiply the calculated dose (in grams) by 5.

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

    (IGSC) HyQvia

    Infuse the two components of HyQvia sequentially, beginning with the recombinant human hyaluronidase.
    Initiate the IGSC within 10 minutes of the recombinant human hyaluronidase infusion.
    Initiation of treatment:
    • Increase dose and frequency from a 1-week dose to a 3- or 4-week dose (see ramp-up schedule below)
    • For patients previously on another IG treatment, administer the first dose of HyQvia approximately one week after the last infusion of their previous treatment
    Initial dosage ramp-up schedule
    (e.g., every 4-week dosing):
    Week 1: [1-week dose interval] 1/4 of target dose
    Week 2: [2-week dose interval] 1/2 of target dose
    Week 3: no infusion
    Week 4: [3-week dose interval] 3/4 of target dose
    Week 5: no infusion
    Week 6: no infusion
    Week 7: [4-week dose interval] target dose, repeat every 4 weeks
    Switching from IGIV:
    Administer at the same dose and frequency as the previous intravenous treatment, after the initial dose ramp-up

    Naive to IG treatment or switching from IGSC:
    300 to 600 mg/kg at 3 to 4 week intervals, after initial ramp-up

    Dose adjustments:
    See details in prescribing information

    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 26, 2015.
    2. Immune Globulin. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 26, 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 [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. Hayes. Medical Technology Directory. Intravenous Immunoglobulin for Neurological Diseases. February 6, 2006. Updated July 30, 2010.
    11. Blaes F. Paraneoplastic Neurological Syndromes - Diagnosis and Management. Alternatively "Diagnosis and Management of Paraneoplastic Neurological Syndrome." B Curr Pharm Des. 2012 May 16. [Epub ahead of print]
    12. Briani C, Vitaliani R, Grisold W, et al. Spectrum of paraneoplastic disease associated with lymphoma. Neurology. 2011;76(8):705.
    13. Pless M, Ronthal M. Treatment of opsoclonus-myoclonus with high-dose intravenous immunoglobulin. Neurology 1996;46:583-4.
    14. http://www.omsusa.org/IVIG%201g%20infusion%20protocol.pdf
    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. Medscape. http://emedicine.medscape.com/article/1156965-treatment. Accessed June 25, 2015.
    20. Octagam 10% [Prescribing Information]. Hoboken, NJ; Octapharma USA: July 2014.
    21. 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.