Ferric Carboxymaltose (Injectafer) Form

Ferric carboxymaltose (Injectafer®) injection is an iron replacement product. FDA Approved Indication(s) Injectafer is indicated for treatment of:
• Iron deficiency anemia (IDA) in adult and pediatric patients 1 year of age and older who have either intolerance to oral iron or an unsatisfactory response to oral iron IDA in adult patients who have non-dialysis dependent chronic kidney disease (CKD) Iron deficiency in adult patients with heart failure and New York Heart Association (NYHA) class II/III to improve exercise capacity. • • Policy/Criteria Provider must submit documentation (including 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 Injectafer is medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Iron Deficiency Anemia with Chronic Kidney Disease (must meet all):

1. Diagnosis of IDA and CKD;
   2. IDA is confirmed by either of the following: a. Transferrin saturation (TSAT) ≤ 30%; b. Serum ferritin ≤ 500 ng/mL;
2. If CKD does not require hemodialysis or peritoneal dialysis, oral iron therapy is not optimal due to any of the following: a. TSAT < 12%; b. Hgb < 7 g/dL; c. Symptomatic anemia; d. Severe or ongoing blood loss; e. Oral iron intolerance; f. Unable to achieve therapeutic targets with oral iron; g. Co-existing condition that may be refractory to oral iron therapy;

3. Member meets both of the following (a and b): a. Failure of both of the following, unless clinically significant adverse effects are experienced or both are contraindicated: Ferrlecit® and Venofer®; Page 1 of 9

   CLINICAL POLICY Ferric Carboxymaltose b. If member has satisfied criteria 4a above, failure of generic Feraheme®, unless contraindicated or clinically significant adverse effects are experienced;

   5. Dose does not exceed two 750 mg elemental iron infusions/injections or a single 1,000 mg elemental iron infusion/injection. Approval duration: 3 months B. Iron Deficiency Anemia without Chronic Kidney Disease (must meet all):
4. Diagnosis of IDA confirmed by any of the following: a. Serum ferritin < 15 ng/mL or < 30 ng/mL if pregnant; b. Serum ferritin ≤ 41 ng/mL and Hgb < 12 g/dL (women)/< 13 g/dL (men); c. TSAT < 20%; d. Absence of stainable iron in bone marrow; e. Increased soluble transferring receptor (sTfR) or sTfR-ferritin index; f. Increased erythrocyte protoporphyrin level;
5. Oral iron therapy is not optimal due to any of the following: a. TSAT < 12%; b. Hgb < 7 g/dL; c. Symptomatic anemia; d. Severe or ongoing blood loss; e. Oral iron intolerance; f. Unable to achieve therapeutic targets with oral iron; g. Co-existing condition that may be refractory to oral iron therapy;
6. At the time of the request, member does not have CKD;
   4. Member meets both of the following (a and b): a. Failure of two of the following, unless clinically significant adverse effects are experienced or all are contraindicated: Ferrlecit, Infed®, or Venofer; b. If member has satisfied criteria 4a above, failure of generic Feraheme, unless contraindicated or clinically significant adverse effects are experienced;
   5. Dose does not exceed two 750 mg elemental iron infusions/injections or a single 1,000 mg elemental iron infusion/injection. Approval duration: 3 months C. Iron Deficiency with Heart Failure (must meet all):
7. Diagnosis of iron deficiency confirmed by either of the following (a or b): a. Serum ferritin level < 100 ng/mL; b. Serum ferritin level between 100 to 300 ng/mL and TSAT < 20%;
8. Member meets all of the following (a, b, c, and d): a. Hb < 15 g/dL; b. LVEF ≤ 45%; c. NYHA class II or III; d. Age ≥ 18 years;

9. Dose does not exceed 1,000 mg elemental iron per infusion/injection. Approval duration: 3 months Page 2 of 9

   CLINICAL POLICY Ferric Carboxymaltose D. 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.
    II. Continued Therapy A. Iron Deficiency Anemia with Chronic Kidney Disease (must meet all):
12. 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);
13. Documentation of one of the following laboratory results measured since the last IV iron administration (a or b): a. TSAT ≤ 30%; b. Serum ferritin ≤ 500 ng/mL;
14. Member meets both of the following (a and b): a. Failure of both of the following, unless clinically significant adverse effects are experienced or both are contraindicated: Ferrlecit and Venofer; b. If member has satisfied criteria 3a above, failure of generic Feraheme, unless contraindicated or clinically significant adverse effects are experienced;
15. If request is for a dose increase, new dose does not exceed two 750 mg elemental iron infusions/injections or a single 1,000 mg elemental iron infusion/injection. Approval duration: 3 month B. Iron Deficiency Anemia without Chronic Kidney Disease (must meet all):

16. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; Page 3 of 9

    CLINICAL POLICY Ferric Carboxymaltose 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);

17. Documentation of one of the following laboratory results measured since the last IV iron administration (a, b, c, d, e, or f): a. Serum ferritin < 15 ng/mL or < 30 ng/mL if pregnant; b. Serum ferritin ≤ 41 ng/mL and Hb < 12 g/dL (women)/< 13 g/dL (men); c. TSAT < 20%; d. Absence of stainable iron in bone marrow; e. Increased sTfR or sTfR-ferritin index; f. Increased erythrocyte protoporphyrin level;
18. At the time of the request, member does not have CKD;
    4. Member meets both of the following (a and b): a. Failure of two of the following, unless clinically significant adverse effects are experienced or all are contraindicated: Ferrlecit, Infed, or Venofer; b. If member has satisfied criteria 4a above, failure of generic Feraheme, unless contraindicated or clinically significant adverse effects are experienced;
19. If request is for a dose increase, new dose does not exceed two 750 mg elemental iron infusions/injections or a single 1,000 mg elemental iron infusion/injection. Approval duration: 3 months C. Iron Deficiency with Heart Failure (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);
20. Documentation of one of the following laboratory results measured since the last IV iron administration (a or b): a. Serum ferritin <100 ng/mL; b. Serum ferritin 100 to 300 ng/mL with transferrin saturation < 20%;
    3. If request is for a dose increase, new dose does not exceed a single 1,000 mg elemental iron infusion/injection.
       Approval duration: 3 months D. Other diagnoses/indications (must meet 1 or 2):

21. 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 Page 4 of 9

    CLINICAL POLICY Ferric Carboxymaltose 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

22. 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 policy – CP.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 CKD: chronic kidney disease ESA: erythropoiesis stimulating agent Hb: hemoglobin IDA: iron deficiency anemia LVEF: left ventricular ejection fraction NYHA: New York Heart Association TSAT: transferrin saturation sTfR: soluble transferring receptor 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 and may require prior authorization. Drug Name Dosing Regimen Dose Limit/ Maximum Dose Examples of OTC Oral Iron Formulations* Ferrous fumarate (Ferretts, Ferrimin 150) Ferrous gluconate (Ferate) Ferrous sulfate (BProtected Pedia Iron, Fer-In-Sol, FeroSul, Iron Supplement, Iron Supplement Childrens, Slow Fe, Slow Iron) Polysaccharide-iron complex (EZFE 200, Ferrex 150, Ferrix x- 150, IFerex 150, NovaFerrum 125, NovaFerrum, NovaFerrum Pediatric Drops, Nu-Iron, Poly-Iron 150) Injectable iron agents Sodium ferric gluconate (Ferrlecit) Infed (iron dextran) Venofer (iron sucrose) Ferumoxytol (Feraheme)
    Varies Varies Page 5 of 9

    CLINICAL POLICY Ferric Carboxymaltose 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. *Oral formulations include elixirs, liquids, solutions, syrups, capsules, and tablets - including delayed/extended-release tablets.
    Appendix C: Contraindications/Boxed Warnings • Contraindication(s): Hypersensitivity to Injectafer or any of its inactive components. • Boxed warning(s): None reported. V. Dosage and Administration
    Indication IDA
    Dosing Regimen ≥ 50kg (110lb): two 750 mg doses by IV infusion separated by at least 7 days for a cumulative dose of 1,500 mg per course.
    In adults: Alternatively, a single-dose treatment course may be administered as 15 mg/kg to a maximum of 1,000 mg. < 50kg (110lb): two doses by IV infusion separated by at least 7 days as 15 mg/kg body weight.
    Iron deficiency with heart failure and NYHA Class II/III (adults) < 70 kg (154lb):
    Hb < 10 g/dL: 1,000 mg on day 1, then 500 mg on week 6 Hb 10 to 14 g/dL: 1,000 mg on day 1 Hb > 14 to < 15 g/dL: 500 mg on day 1 Maximum Dose Two dose treatment course: 750 mg per dose (up to 1,500 mg) Single dose treatment course: 1,000 mg Treatment may be repeated
    See dosing regimen ≥ 70 kg (154lb):
    Hb < 10 g/dL: 1,000 mg on day 1, then 1,000 mg on week 6 Hb 10 to 14 g/dL: 1,000 mg on day 1, then 500 mg on week 6 Hb > 14 to < 15 g/dL: 500 mg on day 1 Maintenance dose: 500 mg at 12, 24 and 36 weeks. VI. Product Availability
    Intravenous solution single-dose vial: 100 mg/2 mL, 750 mg/15 mL, 1,000 mg/20 mL VII.