CYSTADANE, Betaine Form

Betaine (Cystadane®) is a methylating agent.
FDA Approved Indication(s) Cystadane is indicated in pediatric and adult patients for the treatment of homocystinuria to decrease elevated homocysteine blood concentrations. Included within the category of homocystinuria are: • Cystathionine beta-synthase (CBS) deficiency • 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency • Cobalamin cofactor metabolism (cbl) defect Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Cystadane is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Homocystinuria (must meet all):

1. Diagnosis of homocystinuria associated with one of the following (a, b, or c): a. CBS deficiency; b. MTHFR deficiency; c. cbl defect;
2. Prescribed by or in consultation with metabolic or genetic disease specialist;
   3. Dose does not exceed 20 g per day. Approval duration:
      Medicaid/HIM – 6 months
      Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):

3. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: Page 1 of 5

   CLINICAL POLICY Betaine CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

4. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Homocystinuria (must meet all):
5. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
   2. Member is responding positively to therapy;
   3. If request is for a dose increase, new dose does not exceed 20 g per day.
      Approval duration:
      Medicaid/HIM – 12 months
      Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):
6. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

7. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
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   CLINICAL POLICY Betaine III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
   IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CBL: cobalamin cofactor metabolism CBS: cystathionine beta-synthase FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
   Not applicable MTHFR: 5,10-methylenetetrahydrofolate reductase Appendix C: Contraindications/Boxed Warnings None reported
   Appendix D: General Information • Normal homocysteine levels range from 5 to 15 µmol/L • Hyperhomocysteinemia has been classified as follows: o Moderate: 15 to 30 µmol/L o Intermediate: 30 to 100 µmol/L o Severe: > 100 µmol/L V. Dosage and Administration
   Indication Homocystinuria Dosing Regimen 3 g PO BID Maximum Dose 150 mg/kg/day (20 g/day) VI. Product Availability
   Powder for oral solution: 180 g VII.