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Prior Authorization Protocol

ZAVESCAR (miglustat), CERDELGATM (eliglustat)



NATL

Coverage of drugs is first determined by the memberís pharmacy or medical benefit. Please consult with or refer to the Evidence of Coverage document.
  1. FDA Approved Indications:
    • Zavesca: Monotherapy for treatment of adult patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement is not a therapeutic option (e.g. due to constraints such as allergy, hypersensitivity, or poor venous access).
    • Cerdelga: For the long-term treatment of adult patients with Gaucher disease type 1 (GD1) who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) as detected by an FDA-cleared test.
  2. Health Net Approved Indications and Usage Guidelines:
    • Diagnosis of type 1 Gaucher disease
    AND
    • Diagnosis confimed by measurement of beta-glucocerebrosidase activity (in leukocytes or skin fibroblasts) of less than 30% of normal values OR deoxyribonucleic acid (DNA) testing (mutations in the glucocerebrosidase gene)
    AND
    • Patient exhibits clinical signs and symptoms of the disease, including anemia, thrombocytopenia, skeletal disease, or visceromegaly (liver or spleen enlargement)
    AND
    • Failure or clinically significant adverse effects to enzyme replacement therapy (CerezymeR, VPRIVR, or ElelysoTM)
    AND
    • Patient is age >18 years old at initiation of therapy

    AND

    • For Cerdelga requests: An FDA-cleared genotyping test (see General Information section below) has determined that this patient is a CYP2D6 extensive metabolizer (EM), intermediate metabolizer (IM), or poor metabolizer (PM).
  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.
    • For Cerdelga requests: EMs or IMs taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor AND IMs or PMs taking a strong CYP3A inhibitor
  4. General Information:
    • Zavesca is distributed through Accredo (specialty pharmacy provider) only to certified physicians. For additional information, call 877-472-1326 or visit www.zavesca.com.
    • There is currently insufficient evidence that supports the combination use of enzyme replacement therapy with Zavesca or Cerdelga.
    • A CYP2D6 genotyping program is available through LabCorp, using an FDA-cleared test. This Genzyme-funded program can help physicians identify patients who are eligible for treatment with Cerdelga through an FDA-cleared test. Physicians enroll with LabCorp then complete a Test Request form for each patient requiring genotyping. For more information call 1-800-745-4447, option #2.
    • Patients who are CYP2D6 ultra-rapid metabolizers (URMs) may not achieve adequate concentrations of Cerdelga to achieve a therapeutic effect.
    • A specific dosage cannot be recommended for those patients whose CYP2D6 genotype cannot be determined (indeterminate metabolizers).
    • To reduce the risk of potentially significant adverse reactions, the dose of Cerdelga should be reduced to 84 mg orally once daily for CYP2D6 EMs and IMs taking strong or moderate CYP2D6 inhibitors OR CYP2D6 EMs taking strong or moderate CYP3A inhibitors.
    • Cerdelga is contraindicated in the following patients due to the risk of significantly increased Cerdelga plasma concentrations which may result in prolongation of the PR, QTc, and/or QRS cardiac intervals that could result in cardiac arrhythmias: EMs or IMs taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor AND IMs or PMs taking a strong CYP3A inhibitor. Examples of strong or moderate CYP2D6 inhibitors include paroxetine, fluoxetine, bupropion, quinidine, cinacalcet and terbinafine. Examples of strong CYP3A inhibitors include ketoconazole, itraconazole, clarithromycin, nefazodone, HIV protease inhibitors. Examples of moderate CYP3A inhibitors include fluconazole, ciprofloxacin, diltiazem, verapamil and erythromycin.
  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose
    CerezymeR (imiglucerase)*

    2.5 units/kg via IV infusion 3 times weekly to 60 units/kg once every 2 weeks.

    240 units/kg every 2 weeks

    VPRIVTM (velaglucerase alpha)*

    60 units/kg via IV infusion every other week

    60 units/kg every other week

    Elelyso (taliglucerase alfa)*

    60 units/kg via IV infusion every other week

    73 units/kg every other week

    * Requires Prior Authorization
  6. Recommended Dosing Regimen and Authorization Limit:
    Drug Dosing Regimen Authorization Limit

    Zavesca

    100 mg PO TID

    Length of Benefit

    Cerdelga

    CYP2D6 EMs and IMs
    84 mg PO BID
    CYP2D6 PMs
    84 mg PO QD

    Length of Benefit

  7. Product Availability:
    Zavesca capsule: 100 mg packed in blister cards of 18 (5 blister cards per carton)
    Cerdelga capsule: 84 mg
  8. References:
    1. Zavesca [Prescribing information] South San Francisco, CA: Actelion Pharmaceuticals; February 2014.
    2. MicromedexR Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed July 7, 2015.
    3. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed July 7, 2015.
    4. Clinical Pharmacology Web site. Available at: http://www.clinicalpharmacology-ip.com/. Accessed July 7, 2015.
    5. Cerdelga [Prescribing Information]. Waterford, Ireland: Genzyme Corp; August 2014.
    6. Lukina E, et al. Eliglustat, an investigational oral therapy for Gaucher disease type 1: Phase 2 trial results after 4 years of treatment. Blood Cells Mol. Diseases (2014), http://dx.doi.org/10.1016/j.bcmd.2014.04.002.
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.