ZINECARD, Dexrazoxane HCl TOTECT, Dexrazoxane HCl Form

Dexrazoxane (Totect®) is a cytoprotective agent. FDA Approved Indications Totect is indicated for:
• Reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose of 300 mg/m2 and who will continue to receive doxorubicin therapy to maintain tumor control. Do not use Totect with doxorubicin initiation. • Treatment of extravasation resulting from intravenous anthracycline chemotherapy. 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 Totect is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Doxorubicin-Induced Cardiomyopathy (must meet all):

1. Prescribed to reduce the incidence or severity of cardiomyopathy associated with doxorubicin;

2. Prescribed by or in consultation with an oncologist or hematologist;

   3. One of the following (a, b, c, d, or e): a. Age ≥ 18 years, and member has received a cumulative doxorubicin dose of ≥ 300 mg/m2;
      b. Request is for pediatric Ph-negative ALL as part of the DFCI ALL Protocol 11- 001 or 16-001 in members with an anticipated cumulative anthracycline dose ≥ 250 mg/m2 of doxorubicin equivalent or radiation with potential impact to the heart (e.g., radiation to chest, abdomen, spine, or total body irradiation) (off- label); c. Request is for pediatric aggressive mature B-cell lymphomas or pediatric Hodgkin lymphoma (off-label); d. Request is for Wilms Tumor (nephroblastoma), and member has a planned cumulative dose of doxorubicin ≥ 150 mg/m2 (off-label); e. Request for soft tissue sarcoma, and member has a planned cumulative dose of doxorubicin ≥ 250 mg/m2 (off-label);
      Page 1 of 7

   CLINICAL POLICY Dexrazoxane

3. Will be used concurrently with doxorubicin;
   5. Request meets one of the following (a or b): a. Dose does not exceed 10 times the dose of doxorubicin (e.g., dexrazoxane 500 mg/m2 for member receiving doxorubicin 50 mg/m2) given with each doxorubicin dose; b. Dose 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: 12 months or duration of doxorubicin therapy, whichever is less B. Anthracycline-Induced Extravasation (must meet all):
   6. Diagnosis of anthracycline-induced extravasation;
   7. Prescribed by or in consultation with an oncologist;
   8. Age ≥ 18 years;
   9. Dose does not exceed 2,000 mg per day on days 1 and 2, and 1,000 mg on day 3. Approval duration: 3 days C. Other diagnoses/indications (must meet 1 or 2):
4. 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
5. 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. Doxorubicin-Induced Cardiomyopathy (must meet all):
6. 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);

7. Member continues to receive doxorubicin;

   3. Member is responding positively to therapy; Page 2 of 7

   CLINICAL POLICY Dexrazoxane

8. Request meets one of the following (a or b): a. Dose does not exceed 10 times the dose of doxorubicin (e.g., dexrazoxane 500 mg/m2 for member receiving doxorubicin 50 mg/m2) given with each doxorubicin dose; b. Dose 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: 12 months or duration of doxorubicin therapy, whichever is less B. Anthracycline-Induced Extravasation
9. Re-authorization is not permitted. Member must meet the initial approval criteria. Approval duration: Not applicable C. Other diagnoses/indications (must meet 1 or 2):
10. 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

11. 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.
    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 – 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 ALL: acute lymphoblastic leukemia FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
    Not applicable Page 3 of 7

    CLINICAL POLICY Dexrazoxane Appendix C: Contraindications/Boxed Warnings None reported V. Dosage and Administration Indication Doxorubicin-induced cardiomyopathy Anthracycline- induced extravasation Dosing Regimen Give dexrazoxane at a ratio of 10:1 with the doxorubicin dose as an IV infusion over 15 minutes and within 30 minutes before doxorubicin is given. Day 1: 1,000 mg/m2 Day 2: 1,000 mg/m2 Day 3: 500 mg/m2 Maximum Dose Not applicable Day 1: 2,000 mg Day 2: 2,000 mg Day 3: 1,000 mg Give Totect as an IV infusion over 1-2 hours and within 6 hours of extravasation. Treatment on days 2 and 3 should start at the same hour (+/-3 hours) as day 1. VI. Product Availability
    Single-dose vial, IV powder for solution: 500 mg VII.