Intravenous Iron Replacement Therapy Form

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PART B DRUG MEDICAL/PHARMACY

Effective Date: 01/06/2026
Policy # Intravenous Iron Replacement Therapy Intravenous Iron Replacement Therapy Feraheme (ferumoxytol) Injectafer (ferric carboxymaltose) Monoferric (ferric derisomaltose) Last Review Date Applicable to: 11/17/2025 Medicare Advantage Elevance Health HMO Blue Shield Trio Approver’s Name & Title QI & UM Drug Subcommittee

Aspire Health Plan (AHP) applies medical drug clinical criteria as a reference for medical policy information only. Federal and state laws or requirements, contract language, and Plan benefit may take precedence over the application of these clinical criteria. Please consult the applicable certificate or contract for benefit details. This policy is subject to revision at the discretion of the Plan and is therefore subject to change. Refer to the disclaimer section below for more information.

POLICY

This policy addresses the coverage for Intravenous Iron Replacement Therapy as outlined by the Centers for Medicare and Medicaid Services (CMS) guidelines (NCD 110.10) and is intended to support safe and appropriate use of therapy for Aspire Health Plan members.

Aspire Health Plan (AHP) adheres to Medicare guideline as outlined in National Coverage Determination (NCD) 110.10 Intravenous Iron Therapy and will follow the coverage determination under the 'Indications and Limitations of Coverage' section as per the NCD:

• Effective December 1, 2000, Medicare covers sodium ferric gluconate complex in sucrose injection as a first-line treatment of iron deficiency anemia when furnished intravenously to patients undergoing chronic hemodialysis who are receiving supplemental erythropoeitin therapy.

• Effective October 1, 2001, Medicare also covers iron sucrose injection as a first-line treatment of iron deficiency anemia when furnished intravenously to patients undergoing chronic hemodialysis who are receiving supplemental erythropoeitin therapy.

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LOWER MOLECULAR WEIGHT IRON COMPLEXES The following intravenous iron replacements are NOT subject to the coverage criteria in this policy. NO prior authorization or step therapy is required for Venofer, Ferrlecit, and Infed. Product Name HCPCS Codes Description Venofer (iron sucrose) J1756 Injection, ferumoxytol, for treatment of iron deficiency anemia (Feraheme), 1mg (non-esrd use) Injection, ferumoxytol, for treatment of iron deficiency anemia 1mg (Feraheme) (for esrd on dialysis) Available as: Single-Dose vials: 510 mg/17 mL Ferrlecit (sodium ferric gluconate complex) J2916 Injection, ferric carboxymaltose (Injectafer), 1 mg; 1 billable unit = 1 mg Available as: Single-dose vials: 100 mg/2 mL; 750 mg/15 mL; 1,000 mg/20 mL Infed (iron dextran) J1750 Injection, ferric derisomaltose, 10 mg: 1 billable unit = 10 mg Available as: Single-dose vials: 100 mg/mL; 500 mg/5 mL; 1,000 mg/10 mL

APPLICABLE HCPCS

HIGHER MOLECULAR WEIGHT IRON COMPLEXES PREFERRED DRUG: NO PRIOR AUTHORIZATION / NO STEP THERAPY Product Name HCPCS Codes Description Feraheme (ferumoxytol) PREFERRED DRUG: No PA, No Step Therapy Q0138 Q0139 Injection, ferumoxytol, for treatment of iron deficiency anemia (Feraheme), 1mg (non-esrd use) Injection, ferumoxytol, for treatment of iron deficiency anemia 1mg (Feraheme) (for esrd on dialysis) Available as: Single-Dose vials: 510 mg/17 mL NON-PREFERRED DRUGS: PRIOR AUTHORIZATION + STEP THERAPY REQUIRED Injectafer (ferric carboxymaltose) J1439 Injection, ferric carboxymaltose (Injectafer), 1 mg; 1 billable unit = 1 mg Available as: Single-dose vials: 100 mg/2 mL; 750 mg/15 mL; 1,000 mg/20 mL Monoferric (ferric derisomaltose) J1437 Injection, ferric derisomaltose, 10 mg: 1 billable unit = 10 mg Available as: Single-dose vials: 100 mg/mL; 500 mg/5 mL; 1,000 mg/10 mL

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DEFINITIONS

Iron deficiency is a common condition in end stage renal disease (ESRD) patients undergoing hemodialysis. Iron is a critical structural component of hemoglobin, a key protein found in normal red blood cells (RBCs) which transports oxygen. Without this important building block, anemic patients experience difficulty in restoring adequate, healthy RBCs that improve hematocrit levels. Clinical management of iron deficiency involves treating patients with iron replacement products while they undergo hemodialysis. Body iron stores can be supplemented with either oral or intravenous (IV) iron products.

For the purposes of this policy, Iron Deficiency Anemia is defined as:

• Iron Deficiency Anemia (IDA) Without Chronic Kidney Disease (CKD) or Acute or Chronic Inflammatory Conditions:

• Adults and pediatric patients ≥ 12 years: Serum ferritin < 30 ng/mL or transferrin saturation (TSAT) < 20% or an absence of stainable iron in bone marrow

  • Iron Deficiency Anemia (IDA) With CKD or Acute or Chronic Inflammatory Conditions: Serum ferritin < 100 ng/mL or TSAT < 20%. If serum ferritin is 100-300 ng/mL, TSAT < 20% is required to confirm iron deficiency.

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CLINICAL CRITERIA

I. INITIAL CRITERIA The requested intravenous iron replacement product will be covered in accordance with National Coverage Determination (NCD) 110.10 Intravenous Iron Therapy for patients undergoing chronic hemodialysis who are also receiving supplemental erythropoietin therapy. The NCD does not address coverage of IV iron therapy in patients with iron deficiency anemia who are not on dialysis or not receiving erythropoietin.

For all other conditions, this clinical policy is intended to ensure medical necessity and appropriate coverage. Member must ALL of the following criteria:

A. Documented diagnosis of ONE of the following as indicated by FDA approved product labeling†, CMS- approved compendia‡ or National Comprehensive Cancer Network (NCCN) as a Category 1 or 2A recommendation, including:

1. IRON DEFICIENCY ANEMIA

   a. Iron Deficiency Anemia due to Chronic Kidney Disease (CKD)† • No PA, No Step Therapy: Feraheme†

   b. Iron Deficiency Anemia in patients intolerant to or who have had unsatisfactory response to oral iron† • No PA, No Step Therapy: Feraheme† • PA/Step Therapy Required: Injectafer†; Monoferric†

   c. Iron Deficiency Anemia in Non-Dialysis-Dependent Chronic Kidney Disease (NDD- CKD)† • PA/Step Therapy Required: Injectafer†; Monoferric†

2. IRON DEFICIENCY WITH HEART FAILURE†
   • PA/Step Therapy Required: Injectafer (ferric carboxymaltose)†

3. CANCER- AND CHEMOTHERAPY-INDUCED ANEMIA‡
   • PA/Step Therapy Required: Injectafer (ferric carboxymaltose)‡

   NOTE: All other prescribed uses or conditions for will be evaluated based on Aspire Health Plan’s clinical policy for “Off-Label Use of Drugs and Biologic Agents.”

   AND B. Member meets ONE of the following with documentation:

4. Inadequate response to a consistent trial of ORAL iron, or documented adverse events or labeled contraindication to ORAL iron therapy, or

5. Diagnosis or condition in which oral iron is not appropriate, includes ANY of the following: a. Unable to tolerate gastrointestinal side effects of oral iron b. Malabsorption syndrome c. Gastric surgery that impairs the intestinal absorption of oral iron, d. Severe or ongoing blood loss e. Second trimester of pregnancy with hemoglobin <10.5g f. Third trimester of pregnancy g. Currently undergoing treatment for an oncology indication; prescribed for cancer or chemo-related anemia

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II. REAUTHORIZATION / CONTINUATION OF THERAPY CRITERIA Applicable to AHP members who have previously received authorization of treatment for the requested drug product OR newly enrolled members established on the requested product within the previous year.

A. The requested Intravenous Iron Replacement product may be authorized for continuation of therapy when initial criteria have been met AND there is documentation of beneficial response from previous course of treatment, including but laboratory results demonstrating need for additional therapy. AND B. The prescriber attests to, or the clinical reviewer has found, no evidence of intolerable adverse effects or unacceptable toxicity from intravenous iron replacement product therapy.

STEP THERAPY

Step therapy criteria do not apply for members who are currently being treated with the requested medications. Step therapy is only applied for members that are new to therapy (have not received the requested drug in the last 365 days.

Venofer (iron sucrose), Ferrlecit (sodium ferric gluconate complex), and Infed (iron dextran) are intravenous iron replacements are NOT subject to the coverage criteria policy. NO prior authorization or step therapy is required.

A. PREFERRED PRODUCT: Feraheme (ferumoxytol) --No PA, No Step Therapy required.

B. NONPREFERRED PRODUCTS: Injectafer (ferric carboxymaltose), Monoferric (ferric derisomaltose)

Authorization for a non-preferred intravenous iron product biosimilars may be authorized when the clinical criteria above are met AND the member meets the following criteria for a non-preferred drug:

1. Inadequate response to a trial of one or more of the preferred products; or

2. History of contraindication or adverse event(s) to one or more of the preferred products; or

3. Member has been on the requested product in the past 365 days; or

4. Documented diagnosis is for a medically necessary indication not indicated in the preferred product.

   NOTE: While IV iron products generally demonstrate similar efficacy in treating iron deficiency anemia, their pharmacokinetic differences and safety profiles can influence their suitability for specific patients. Prescriber: Please submit all relevant clinical documentation for review.

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DOSAGE AND AUTHORIZATION TIMEFRAMES

1. RECOMMENDED DOSAGE: Dose and frequency should be consistent with FDA labeling, NCCN, or *CMS recognized compendia. Refer to product-specific labeling for complete dosing information.

2. QUANTITY LIMIT: Based on FDA labeling or *CMS recognized compendia for individual product. The RECOMMENDED quantity limit is as follows.

   *CMS recognized compendia: American Hospital Formulary Service‐Drug Information (AHFS‐DI); National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium; Truven Health Analytics Micromedex DrugDEX; Elsevier/Gold Standard Clinical Pharmacology; Wolters Kluwer Lexi‐ Drugs)

   • Feraheme (ferumoxytol): 1020 mg per 28 days • Injectafer (ferric carboxymaltose) a. Iron Deficiency Anemia: For patients weighing 50 kg or more: 1500 mg per 28 days (2 dose course), OR 15 mg/kg (max 1000 mg) for single dose treatment course; <50 kg: 15 mg/kg body weight in two doses.

   b. Iron Deficiency with Heart Failure: 500mg or 1000mg on Day 1 and Week 6 (depending on weight and hemoglobin) followed by 500mg weeks 12, 24, and 36

   • Monoferric (ferric derisomaltose): For patients weighing 50 kg or more: 1000 mg; For patients weighing less than 50 kg: 20 mg/kg actual body weight per 28 days

3. AUTHORIZATION PERIOD • Initial authorization: 3 months • Continuation of Therapy: 6 months NOTE: There are no data available to guide dosing beyond 36 weeks for iron deficiency with heart failure (Injectafer Prescribing Information)

4. Authorization is limited to the submitted request that was reviewed. Any modifications to the diagnosis or prescribed indication necessitates a new prior authorization request.

   DRUG INFORMATION

   PHARMACOLOGIC CATEGORY: Iron Preparations

   PRODUCTS: Feraheme (ferumoxytol), Injectafer (ferric carboxymaltose), Monoferric (ferric derisomaltose) ROUTE OF ADMINISTRATION: Intravenous, Subcutaneous FDA-APPROVED INDICATIONS Feraheme (ferumoxytol injection) indicated for the treatment of iron deficiency anemia in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron, or for patients who have chronic kidney disease.

   Injectafer (ferric carboxymaltose) is an iron replacement product indicated for the treatment of iron deficiency anemia in adult and pediatric patients 1 year of age and older who have intolerance to oral iron or have had unsatisfactory response to oral iron; and adult patients who have non-dialysis dependent CKD. Injectafer is also indicated for the treatment of iron deficiency in adult patients with heart failure and New York Heart Association class II/III to improve exercise capacity.

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Monoferric (ferric derisomaltose) is an iron replacement product indicated for the treatment of iron deficiency anemia in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron or who have nonhemodialysis dependent chronic kidney disease. COMPENDIAL APPROVED (OFF-LABELED) USES: Refer to CMS-approved compendia for the relevant off-label use.

CONTRAINDICATIONS: Hypersensitivity to the product, including inactive components. Feraheme is also contraindicated in patients with a history of allergic reaction to any intravenous iron product.

BLACK BOXED WARNING: Feraheme (ferumoxytol) has a Black Boxed Warning for risk for serious hypersensitivity/anaphylaxis reactions

MONITORING PARAMETERS: Refer to CMS-approved compendia for the relevant off-label use.

CLINICAL SUMMARY / APPENDIX

Both oral and intravenous iron replacement therapies are effective in treating iron deficiency anemia, however their suitability varies depending on patient-specific factors and clinical circumstances.

Oral iron preparations (e.g., ferrous sulfate, ferrous gluconate, ferrous fumarate) are generally recommended as the first-line treatment for iron deficiency anemia in most patients. Oral iron is generally well-tolerated and safe, with the majority of reported adverse effects being mild and tolerable. The majority of patients with iron deficiency anemia, particularly those with mild to moderate anemia and no contraindications to oral therapy, are appropriate for oral iron therapy. Oral iron is readily available, easy to administer, and does not require intravenous access or monitoring. Intravenous iron replacement therapy involves the administration of iron preparations directly into a vein to replenish iron stores and treat iron deficiency anemia. This route of administration bypasses the gastrointestinal tract and allows for rapid and efficient delivery of iron to the body. Intravenous iron may be considered for patients who cannot tolerate oral iron, have conditions that impair iron absorption, or require rapid iron repletion. • Several intravenous iron preparations are available, each with different pharmacokinetic properties and dosing regimens: ― Iron dextran (INFeD) ― Sodium ferric gluconate complex (Ferrlecit) ― Iron sucrose (Venofer) ― Ferumoxytol (Feraheme) ― Ferric carboxymaltose (Injectafer) ― Ferric derisomaltose (Monoferric) • The choice of IV iron may depend on patient-specific factors such as comorbidities, tolerability, and the urgency of iron repletion. • Factors which may influence which product is selected include patient diagnosis, prior treatments, length of infusion, and the number of infusions required to complete the full course of treatment. In 2022, the American Heart Association (AHA), American College of Cardiology (ACC), and Heart Failure Society of America (HFSA) published their clinical practice guidelines for the management of heart failure. Recommendations are provided for select patients with heart failure (HF) and iron deficiency and anemia. The guidelines state: • Iron deficiency is usually defined as ferritin level < 100 μg /L or 100 to 300 μg/L, if the transferrin saturation is < 20%. • Intravenous repletion of iron has been shown to improve exercise capacity and QOL. • Oral iron is not adequate to treat iron deficiency anemia in patients with HF.

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REFERENCES

Government Agency

1. Centers for Medicare and Medicaid Services (CMS). Medicare coverage database: National coverage determination (NCD) [search terms: Intravenous Iron Therapy]. • NCD: Intravenous Iron Therapy Publication. Available from CMS. NCD 110.10

2. Medicare Benefit Policy Manual Chapter 15 Covered Medical and Other Health Services: https://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/Downloads/bp102c15.pdf

   Prescribing Information

3. Feraheme (ferumoxytol) injection [package insert]. Waltham, MA: AMAG Pharmaceuticals, Inc.; June
5. Injectafer (ferric carboxymaltose) injection [package insert]. Shirley, NY: American Regent, Inc.; February 2022.
6. Monoferric (ferric derisomaltose) injection [package insert]. Morristown, NJ: Pharmacosmos Therapeutics Inc.; February 2022.
7. Ferrlecit (sodium ferric gluconate complex in sucrose) injection [package insert]. Bridgewater, NJ: SanofiAventis US LLC; March 2022.
8. Infed (iron dextran) injection [package insert]. Madison, NJ: Allergan USA, Inc.; September 2020.

9. Venofer (iron sucrose) injection [package insert]. Shirley, NY: American Regent, Inc.; October 2020.

   Peer-reviewed Literature, Guidelines, and Consensus

10. Auerbach M. Causes and diagnosis of iron deficiency and iron deficiency anemia in adults. Tirnauer JS, Givens J, Eds. UptoDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com. Accessed on November 2024.
11. KDIGO 2012 clinical practice guideline for anemia in chronic kidney disease. Kidney International Supplements. August 2012; 2(4):279-331.
12. The NCCN Hematopoietic Growth Factors Guidelines in Oncology (Version 2.2024 – December 12,2023). 2023 National Comprehensive Cancer Network, Inc. Available at : https://www.nccn.org.

13. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [published correction appears in Circulation. 2022 May 3;145(18):e1033] [published correction appears in Circulation. 2022 Sep 27;146(13):e185] [published correction appears in Circulation. 2023 Apr 4;147(14):e674]. Circulation. 2022;145(18):e895-e1032. doi:10.1161/CIR.0000000000001063

    IMPORTANT REMINDER

    This Medicare Part B Step Therapy Medical Necessity Guideline is provided for informational purposes only and neither constitutes nor replaces professional medical advice. Physicians, hospitals, and other providers are expected to administer or use drugs/biologicals in the most effective and clinically appropriate manner. Treating physicians and other health care providers is solely responsible for all medical care decisions. In accordance with the member's Evidence of Coverage (EOC), every benefit plan has its own coverage provisions, limitations, and exclusions. In the event of a conflict between this policy and the member's EOC, the member's EOC provisions will take precedence. Aspire Health Plan (AHP) adheres to Medicare guidelines, including National Coverage Determination (NCD), Local Coverage Determinations (LCDs), Local Coverage Articles (LCAs), and other relevant Medicare manuals established by CMS. Compliance with these guidelines is required when applicable. Refer to the CMS website at http://www.cms.hhs.gov. For the most up-to-date Medicare policies and coverage, please search the Medicare Coverage Database. All LCDS are the same for each state within a Jurisdiction. Medicare Part B Administrative Contractor (MAC) for CA LCDs - JE Part B – Noridian (noridianmedicare.com). In the event of a discrepancy between this policy and the Medicare NCD or LCD, the Medicare NCD/LCD will govern.

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This policy is utilized by AHP to determine coverage in the absence of applicable CMS Medicare guidelines. Please refer to the links provided in the References section below to access the Medicare source materials that were used for developing this resource document. This document does not serve as a substitute for the official Medicare source materials that provide detailed information on Medicare coverage requirements. In the event of a conflict between this document and Medicare source materials, the Medicare source materials will take precedence.

The inclusion of a code in this policy does not imply that the health service it describes is covered or not covered. Benefit coverage for health services is determined by the member-specific plan document and applicable laws that may mandate coverage for a particular service. Inclusion of a code does not imply or guarantee reimbursement or payment of a claim. Other Policies and Standards may also apply. Providers are expected to retain or have access to the necessary documentation when requested to support coverage. The use of physician samples or manufacturer discounts does not guarantee later coverage under the provisions of the medical certificate and/or pharmacy benefit. All criteria must be met to obtain coverage of the listed drug product.

POLICY HISTORY

Committee Date Summary of Changes 11/19/2024 New Policy (effective 05/15/2025) 11/17/2025 Added the definition of Iron Deficiency Anemia (IDA)