Last Review Date: 05/02/2024

Date of Origin: 08/29/2017

Dates Reviewed: 08/2017, 07/2018, 07/2019, 07/2020, 06/2021, 12/2021, 09/2022, 07/2023, 12/2023, 05/2024

1. Length of Authorization ¹

Coverage will be provided for 35 days, unless otherwise specified.

• Iron Deficiency in Patients with Heart Failure: Coverage will be provided for 12 weeks (for up to 2 doses) initially and may be renewed every 12 weeks (for 1 dose) up to a total of 3 maintenance doses.

2. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:

• Injectafer 100 mg iron/2 mL single-dose vial: 7 vials per 35 days
• Injectafer 750 mg iron/15 mL single-dose vial: 2 vials per 35 days
• Injectafer 1,000 mg iron/20 mL single-dose vial: 2 vials per 35 days

2. Max Units (per dose and over time) [HCPCS Unit]:

•  1500 billable units per 35 days

3. Initial Approval Criteria ^1-13

Coverage is provided in the following conditions:

• Patient is at least 18 years of age, unless otherwise specified; AND
• Laboratory values must be obtained within 28 days prior to the anticipated date of administration; AND
• Other causes of anemia (e.g., vitamin B-12 deficiency, thalassemia, sideroblastic anemia, etc.) have been ruled out; AND
• Patient does not have a history of allergic reaction to any intravenous iron product; AND
• Other supplemental iron is to be discontinued prior to administration of ferric carboxymaltose; AND

Iron Deficiency Anemia in Non-Dialysis-Dependent Chronic Kidney Disease (NDD-CKD) † ^1,6,12

• Patient must not be receiving dialysis; AND
• Patient has iron-deficiency anemia with a Hemoglobin (Hb) <11.5 g/dL; AND
  • Ferritin ≤100 ng/mL; OR
  • Ferritin ≤300 ng/mL when transferrin saturation (TSAT) ≤30%

Iron Deficiency Anemia in patients intolerant to or who have had unsatisfactory response to oral iron † ^1-3

• Patient is at least 1 year of age; AND
• Patient had an intolerance or inadequate response to a minimum of 14 days of oral iron; AND
• Patient has iron-deficiency anemia with a Hemoglobin (Hb) <12 g/dL; AND
  • Ferritin ≤100 ng/mL; OR
  • Ferritin ≤300 ng/mL when transferrin saturation (TSAT) ≤30%

Cancer- and Chemotherapy-Induced Anemia ‡ ^7,8,14,15

• Used as a single agent; AND
  • Patient has absolute iron deficiency defined as ferritin < 30 ng/mL AND a TSAT < 20%; OR
  • Patient has functional iron deficiency defined as a ferritin > 500 – 800 ng/mL AND a TSAT < 50% with the goal of avoiding allogenic transfusion; OR
• Used in combination with erythropoiesis-stimulating agents (ESAs); AND
  • Patient has absolute iron deficiency defined as ferritin < 30 ng/mL AND a TSAT < 20% and failed to demonstrate an increase in Hb after 4 weeks of IV or oral iron therapy; OR
  • Patient has functional iron deficiency defined as ferritin 30 – 500 ng/mL AND a TSAT < 50% and is receiving myelosuppressive chemotherapy without curative intent

Iron Deficiency in Patients with Heart Failure † ¹

• Patient has New York Heart Association class II/III disease; AND
• Used to improve exercise capacity; AND
• Patient has iron deficiency with hemoglobin < 15 g/dL; AND
  • Ferritin < 100 ng/mL; OR
  • Ferritin is 100 to 300 ng/mL with TSAT <20%

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ^1-13

Coverage may be renewed based on the following criteria:

Iron Deficiency in Patients with Heart Failure

• Patient has hemoglobin < 15 g/dL; AND
• Patient has serum ferritin <100 ng/mL OR serum ferritin 100-300 ng/mL with transferrin saturation <20%; AND
• Patient will receive maintenance doses at weeks 12, 24, and 36 (Refer to dosing table below)

**Note: Patient may ONLY receive the maintenance doses if iron labs meet the aforementioned criteria. Patients not meeting this criteria will not be eligible for renewal.

All Other Indications

• Refer to initiation criteria.

5. Dosage/Administration ^1,7

6. Billing Code/Availability Information

HCPCS Code:

• J1439 – Injection, ferric carboxymaltose, 1 mg; 1 billable unit = 1 mg

NDC(s):

• Injectafer 100 mg iron/2 mL single-dose vial: 00517-0602-xx
• Injectafer 750 mg iron/15 mL single-dose vial: 00517-0650-xx
• Injectafer 1,000 mg iron/20 mL single-dose vial: 00517-0620-xx

7. References

1. Injectafer [package insert]. Shirley, NY; American Regent, Inc. May 2023. Accessed April 2024.
2. Onken JE, Bregman DB, Harrington RA, et al. A multicenter, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia. Transfusion. 2014 Feb;54(2):306-15.
3. Onken JE, Bregman DB, Harrington RA, et al. Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial. Nephrol Dial Transplant. 2014 Apr;29(4):833-42.
4. KDOQI; National Kidney Foundation. Clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease in adults. Am J Kidney Dis. 2006 May;47(5 Suppl 3):S16-85.
5. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney inter., Suppl. 2012; 2: 279–335.
6. Ratcliffe LE, Thomas W, Glen J, et al. Diagnosis and Management of Iron Deficiency in CKD: A Summary of the NICE Guideline Recommendations and Their Rationale. Am J Kidney Dis. 2016 Apr;67(4):548-58.
7. Referenced with permission from the NCCN Drugs and Biologics Compendium (NCCN Compendium^®) ferric carboxymaltose. National Comprehensive Cancer Network, 2024. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES^® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed April 2024.
8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) Hematopoietic Growth Factors Version 3.2024. National Comprehensive Cancer Network, 2024. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES^® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed April 2024.
9. Wish JB. Assessing iron status: beyond serum ferritin and transferrin saturation. Clin J Am Soc Nephrol. 2006 Sep;1 Suppl 1:S4-8.
10. Koch TA, Myers J, Goodnough LT. Intravenous Iron Therapy in Patients with Iron Deficiency Anemia: Dosing Considerations. Anemia. 2015;2015:763576.
11. Steinmetz T, Tschechne B, Harlin O, et al. Clinical experience with ferric carboxymaltose in the treatment of cancer- and chemotherapy-associated anaemia. Ann Oncol. 2013;24(2):475-482.
12. Qunibi WY, Martinez C, Smith M, et al. A randomized controlled trial comparing intravenous ferric carboxymaltose with oral iron for treatment of iron deficiency anaemia of non-dialysis-dependent chronic kidney disease patients. Nephrol Dial Transplant. 2011;26(5):1599-1607.
13. Ponikowski P, van Veldhuisen DJ, Comin-Colet J, et al; CONFIRM-HF Investigators. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency†. Eur Heart J. 2015 Mar 14;36(11):657-68. doi: 10.1093/eurheartj/ehu385.
14. Makharadze T, Boccia R, Krupa A, et al. Efficacy and safety of ferric carboxymaltose infusion in reducing anemia in patients receiving chemotherapy for nonmyeloid malignancies: A randomized, placebo-controlled study (IRON-CLAD). Am J Hematol 2021;96:1639-1646.
15. Toledano A, Luporsi E, Morere JF, et al. Clinical use of ferric carboxymaltose in patients with solid tumours or haematological malignancies in France. Support Care Cancer 2016;24:67-75.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A