Mercaptopurine (Purixan) Form

Mercaptopurine (Purixan®) is a nucleoside metabolic inhibitor that is an analogue of the purine bases adenine and hypoxanthine. FDA Approved Indication(s) Purixan is indicated for the treatment of patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen. 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 Purixan is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia (must meet all):

1. Diagnosis of ALL or acute promyelocytic leukemia (off-label);
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Member must use mercaptopurine tablets, unless one of the following (a, b, or c): a. Mercaptopurine tablets are contraindicated or clinically significant adverse effects are experienced; b. Member has a documented swallowing disorder or an inability to swallow tablets or capsules; c. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E);

2. Request meets one of the following (a or b): a. Dose does not exceed 2.5 mg/kg or 75 mg/m2 per day; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Approval duration: Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less Page 1 of 6

   CLINICAL POLICY
   Mercaptopurine 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: 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. Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia (must meet all):
5. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Purixan for a covered indication and has received this medication for at least 30 days;
6. Member is responding positively to therapy;
   3. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 5 mg/kg or 75 mg/m2 per day; b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).
      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):
7. 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

8. 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 Page 2 of 6

   CLINICAL POLICY
   Mercaptopurine 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.
   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 policy – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ALL: acute lymphoblastic leukemia FDA: Food and Drug Administration NCCN: National Comprehensive Cancer Network Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
   Drug mercaptopurine (Purinethol) Dose Limit/Maximum Dose Dose should be adjusted to maintain an absolute neutrophil count (ANC) at a desirable level Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Dosing Regimen 1.5 to 2.5 mg/kg (50 to 75 mg/m2) PO QD Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • Typical maintenance therapy regimen consists of daily 6-mercaptopurine, weekly methotrexate, and monthly vincristine/prednisone pulses for 2-3 years. • Oral mercaptopurine can have highly variable drug and metabolite concentrations as many factors (e.g. thiopurine S-methyl transferase (TPMT) polymorphisms and drug- drug-interactions with other chemotherapeutic agents) can affect bioavailability and impact the ability of maintenance regimens to prevent disease relapse.
   • Mercaptopurine dose adjustments may be needed to manage clinically significant adverse effects (e.g. myelosuppression including anemia, neutropenia, lymphopenia and thrombocytopenia). Mercaptopurine oral suspension may be more amendable to dose adjustments in patients who continue to have poor clinical response despite dose adjustments with the tablet form. • Micromedex lists mercaptopurine for Crohn’s disease as a Class I recommendation for adults and Class Ia for pediatrics. Ulcerative colitis has a Class IIb recommendation for both adult and pediatrics. Page 3 of 6

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   Mercaptopurine • NCCN treatment guidelines for ALL state that lymphoblastic lymphoma is indistinguishable from ALL based on morphologic, genetic, and immunophenotypic features. Patients with lymphoblastic lymphoma generally benefit from treatment with ALL-like regimens.
   Appendix E: States with Regulations against Redirections in Certain Oncology Settings State Step Therapy Prohibited? Yes Yes FL GA IA LA NV OH PA TN TX Yes Yes Yes Yes Yes Yes Yes Notes For stage 4 metastatic cancer and associated conditions. For stage 4 metastatic cancer. Redirection does not refer to review of medical necessity or clinical appropriateness. For standard of care stage 4 cancer drug use, supported by peer- reviewed, evidence-based literature, and approved by FDA. For stage 4 advanced, metastatic cancer or associated conditions. Exception if “clinically equivalent therapy, contains identical active ingredient(s), and proven to have same efficacy. Stage 3 and stage 4 cancer patients for a prescription drug to treat
   the cancer or any symptom thereof of the covered person Applies to HIM requests only For stage 4 metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer For advanced metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer and associated conditions V. Dosage and Administration Indication ALL Dosing Regimen 1.5 to 2.5 mg/kg (50 to 75 mg/m2) PO QD Maximum Dose 2.5 mg/kg/day or 75 mg/m2/day VI. Product Availability Oral suspension: 2,000 mg/100 mL (20 mg/mL) VII.