DESFERAL, Deferoxamine Mesylate Form

Deferoxamine (Desferal®) is an iron-chelating agent. FDA Approved Indication(s) Desferal is indicated for the treatment of: • Acute iron intoxication o Desferal is an adjunct to, and not a substitute for, standard measures used in treating acute iron intoxication, which may include the following: induction of emesis with syrup of ipecac; gastric lavage; suction and maintenance of a clear airway; control of shock with intravenous (IV) fluids, blood, oxygen, and vasopressors; and correction of acidosis. • Chronic iron overload due to transfusion-dependent anemias o Desferal can promote iron excretion in patients with secondary iron overload from multiple transfusions (as may occur in the treatment of some chronic anemias, including thalassemia). Long-term therapy with Desferal slows accumulation of hepatic iron and retards or eliminates progression of hepatic fibrosis. o Iron mobilization with Desferal is relatively poor in patients under the age of 3 years with relatively little iron overload. The drug should ordinarily not be given to such patients unless significant iron mobilization (e.g., 1 mg or more of iron per day) can be demonstrated. Limitation(s) of use: Desferal is not indicated for the treatment of primary hemochromatosis, since phlebotomy is the method of choice for removing excess iron in this disorder. 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 Desferal is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Acute Iron Intoxication (must meet all):

1. Diagnosis of acute iron intoxication;

2. If request is for brand Desferal, member must use generic deferoxamine, unless contraindicated or clinically significant adverse effects are experienced;

   3. Dose does not exceed 6,000 mg in 24 hours (IM or IV). Approval duration: 1 month Page 1 of 6

   CLINICAL POLICY Deferoxamine B. Chronic Iron Overload due to Transfusion-Dependent Anemias

   1. Diagnosis of chronic iron overload due to transfusion-dependent anemia (e.g., congenital/acquired anemias including thalassemia, sickle cell anemia, aplastic anemia, myelodysplasia);
   2. 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;
   3. If request is for brand Desferal, member must use generic deferoxamine, unless contraindicated or clinically significant adverse effects are experienced;
   4. Dose does not exceed any of the following (a, b, or c): a. SC: 2,000 mg per day; b. IV: 40 mg/kg per day for children; 60 mg/kg per day for adults; c. IM: 1,000 mg per day. Approval duration: 6 months C. Other diagnoses/indications (must meet 1 or 2):
   5. 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
   6. 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 Iron Intoxication
   7. Re-authorization is not permitted. Members must meet initial approval criteria for new cases of acute iron intoxication.
      Approval duration: Not applicable B. Chronic Iron Overload due to Transfusion-Dependent Anemias (must meet all):
   8. 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); Page 2 of 6

   CLINICAL POLICY Deferoxamine

   2. Current documentation (within the last 30 days) shows a serum ferritin level ≥ 500 mcg/L;
   3. If request is for brand Desferal, member must use generic deferoxamine, unless contraindicated or clinically significant adverse effects are experienced;
   4. If request is for a dose increase, new dose does not exceed any of the following (a, b, or c):
      a. SC: 2,000 mg per day; b. IV: 40 mg/kg per day for children; 60 mg/kg per day for adults; c. IM: 1,000 mg per day. Approval duration: 12 months C. Other diagnoses/indications (must meet 1 or 2):
   5. 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
   6. 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 – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents; B. Primary hemochromatosis; C. Parkinson’s disease.
      IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
      Not applicable Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
      Page 3 of 6

   CLINICAL POLICY Deferoxamine o Known hypersensitivity to the active substance o Severe renal disease or anuria, since the drug and the iron chelate are excreted primarily by the kidney • Boxed warning(s): none reported Appendix D: 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 Dosing Regimen Acute iron intoxication 1,000 mg x 1 dose, then 500 mg Q4 hr x 2 doses PRN, then 500 mg Q4-12 hr PRN _ IM route if patient not in shock; IV infusion limited to patients in cardiovascular collapse. 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 Maximum Dose 6,000 mg/24 hr See dosing regimen 40 mg/kg/day (children) 60 mg/kg/day (adults) 1,000 mg/day Chronic iron overload VI. Product Availability
   Vial of lyophilized deferoxamine mesylate: 500 mg VII.