Deferiprone (Ferriprox) Form

Deferiprone (Ferriprox®) is an iron chelator. FDA Approved Indication(s) Ferriprox is indicated for the treatment of transfusional iron overload in adult and pediatric patients (tablets: 8 years of age and older; oral solution: 3 years of age and older) with thalassaemia syndromes, sickle cell disease, or other anemias. Limitation(s) of use: Safety and effectiveness have not been established for the treatment of transfusional iron overload in patients with myelodysplastic syndrome or in patients with Diamond Blackfan anemia. 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 Ferriprox is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Transfusional Iron Overload (must meet all):

1. Diagnosis of transfusional iron overload due to one of the following (a, b, or c): a. Thalassaemia syndromes;
   b. Sickle cell disease;
   c. Other anemia;
2. Member meets one of the following (a or b): a. For Ferriprox tablets: Age ≥ 8 years;
   b. For Ferriprox oral solution: Age ≥ 3 years;
3. Transfusion history of ≥ 100 mL/kg of packed red blood cells (e.g., ≥ 20 units of packed red blood cells for a 40 kg person) and a serum ferritin level > 1,000 mcg/L;
4. Failure of deferoxamine and deferasirox (Exjade®, Jadenu®), unless clinically significant adverse effects are experienced or all are contraindicated; *Prior authorization may be required for deferoxamine and deferasirox

5. Dose does not exceed 99 mg/kg per day.
   Approval duration: 6 months Page 1 of 6

   CLINICAL POLICY Deferiprone 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 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 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 and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Transfusional Iron Overload (must meet all):
   
   1. 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);
8. Current documentation (within the past 30 days) shows a serum ferritin level ≥ 500 mcg/L;
9. If request is for a dose increase, new dose does not exceed 99 mg/kg per day.
   Approval duration: 12 months B. 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 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 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 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 – Page 2 of 6

    CLINICAL POLICY Deferiprone CP.CPA.09 for commercial and CP.PMN.53 for Medicaid, or evidence of coverage documents; B. Parkinson’s disease.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key DFO-DFP: deferiprone-deferoxamine
    FDA: Food and Drug Administration 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 Name Dosing Regimen Dose Limit/ Maximum Dose See dosing regimen 40 mg/kg/day (children) 60 mg/kg/day (adults) deferoxamine (Desferal®) 1,000-2,000 mg SC QD (20-40 mg/kg/day) over 8-24 hours. 20-40 mg/kg IV daily (children) and 40-50 mg/kg IV daily (adults) for 5-7 days per week.
    _ Average dose should not exceed 40 mg/kg/day until growth has ceased.
    500-1,000 mg IM/day 20 to 40 mg/kg (calculated to the nearest whole tablet) PO QD 14 mg/kg (calculated to the nearest whole tablet/sachet) PO QD deferasirox (Exjade) deferasirox (Jadenu) 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. 28 mg/kg/day
    1,000 mg/day 40 mg/kg/day Appendix C: Contraindications/Box Warnings • Contraindication(s): hypersensitivity to deferiprone or to any of the excipients in the formulation. • Boxed warning(s): agranulocytosis and neutropenia Appendix D: Combination Therapy A multicentre randomized open-label trial was designed to assess the effectiveness of long- term sequential deferiprone-deferoxamine (DFO-DFP) versus DFP alone to treat thalassaemia major. The decrease of serum ferritin levels during the treatment period was statistically significantly higher in sequential DFP-DFO patients compared with DFP-alone patients (P = 0.005). Kaplan-Meier survival analysis for the two chelation treatments did not show any statistically significant differences (long-rank test, P = 0.3145). Evidence exists to support the use of combination therapy with Ferriprox (deferiprone) and Desferal (deferoxamine) in patients with severe iron overload or overt iron-related morbidity. Page 3 of 6

    CLINICAL POLICY Deferiprone Appendix E: General Information
    • In FAIRPARK-II, deferiprone, an iron chelator, was associated with worse scores in measures of parkinsonism compared to placebo over a 36-week period in participants with newly diagnosed Parkinson’s disease who had never received levodopa.
    V. Dosage and Administration
    Indication Transfusional iron overload Dosing Regimen Oral tablets: 75 mg/kg PO in 2 or 3 divided doses for a total daily dose of 75 to 99 mg/kg/day in 2 or 3 divided doses Maximum Dose 99 mg/kg/day Oral solution: 25 mg/kg to 33 mg/kg PO TID for a total daily dose of 75 mg/kg to 99 mg/kg VI. Product Availability
    • Oral solution: 100 mg/mL
    • Tablets: 500 mg with functional scoring, 1,000 mg (three times a day) with functional scoring, 1,000 mg (twice a day) with functional scoring VII.