TABLOID, Thioguanine Form

Thioguanine (Tabloid®) is an antimetabolite. FDA Approved Indication(s) Tabloid is indicated for remission induction and remission consolidation treatment of acute nonlymphocytic leukemias [also known as acute myeloid leukemia; AML per the National Cancer Institute’s Dictionary of Cancer Terms]. However, it is not recommended for use during maintenance therapy or similar long-term continuous treatments due to the high risk of liver toxicity. Tabloid is not effective in chronic lymphocytic leukemia, Hodgkin’s lymphoma, multiple myeloma, or solid tumor. 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 Tabloid is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Acute Myeloid Leukemia (must meet all):

1. Diagnosis of AML;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Prescribed for induction or consolidation therapy;
   4. Request meets one of the following (a or b): a. Dose does not exceed 3 mg/kg per day; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant labeled or off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: 3 months B. Acute Lymphoblastic Leukemia (off-label) (must meet all):

2. Diagnosis of acute lymphoblastic leukemia (ALL);

   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age < 65 years;
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   CLINICAL POLICY Thioguanine

3. Disease is one of the following (a or b): a. Philadelphia chromosome-negative; b. For members < 18 years with Philadelphia chromosome-positive ALL: prescribed in combination with Sprycel® or imatinib;
4. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: 3 months C. Glioma (off-label) (must meet all):
5. Diagnosis of recurrent or progressive pilocytic astrocytoma (PA);
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Prescribed in combination with PCV (procarbazine, lomustine, and vincristine; carmustine may be used in place of lomustine);
6. Member has had prior fractionated external beam radiation therapy;
   
   6. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: 3 months D. 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: 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: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or
   2. 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: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
      II. Continued Therapy A. Acute Myeloid Leukemia (must meet all):
8. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Tabloid for a covered indication and has received this medication for at least 30 days;

9. 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 3 mg/kg per day; Page 2 of 7

   CLINICAL POLICY Thioguanine b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant labeled or off-label use (prescriber must submit supporting evidence). Approval duration: 3 months B. Acute Lymphoblastic Leukemia and Glioma (off-label) (must meet all):

10. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Tabloid for a covered indication and has received this medication for at least 30 days;
11. Member is responding positively to therapy;
    3. If request is for a dose increase, new dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: 3 months C. Other diagnoses/indications (must meet 1 or 2):

12. 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: 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: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or

    2. 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: 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 policies – 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 AML: acute myeloid leukemia ALL: acute lymphoblastic leukemia FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
       Not applicable NCCN: National Comprehensive Cancer Network PA: pilocytic astrocytoma Page 3 of 7

    CLINICAL POLICY Thioguanine Appendix C: Contraindications/Boxed Warnings • Contraindication(s): thioguanine should be not used in patients whose disease has demonstrated prior resistance to this drug • Boxed warning(s): none reported V. Dosage and Administration
    Indication Dosing Regimen AML
    Induction and consolidation therapy: • Combination therapy:
    Maximum Dose Varies o Because the usual therapies for adult and pediatric acute nonlymphocytic leukemias involve the use of thioguanine with other agents in combination, physicians responsible for administering these therapies should be experienced in the use of cancer chemotherapy and in the chosen protocol. • Single agent therapy: o On those occasions when single-agent chemotherapy with thioguanine may be appropriate, the usual initial dosage for pediatric patients and adults is approximately 2 mg/kg of body weight per day. If, after 4 weeks on this dosage, there is no clinical improvement and no leukocyte or platelet depression, the dosage may be cautiously increased to 3 mg/kg/day. The total daily dose may be given at one time. Maintenance therapy: • Thioguanine is not recommended for use during maintenance therapy or similar long-term continuous treatments due to the high risk of liver toxicity. VI. Product Availability
    Tablet: 40 mg VII.