What is Feraheme (ferumoxytol)?

What is Feraheme (Ferumoxytol)?

Feraheme (ferumoxytol) is an intravenous iron replacement product consisting of superparamagnetic iron oxide nanoparticles coated with polyglucose sorbitol carboxymethylether, approved for treating iron deficiency anemia in adult patients with chronic kidney disease. 1

Composition and Structure

• Ferumoxytol is a non-stoichiometric magnetite (superparamagnetic iron oxide) with a carbohydrate shell coating, with colloidal particle size of 17-31 nm in diameter and apparent molecular weight of 750 kDa. 1
• Each mL contains 30 mg of elemental iron, 30 mg polyglucose sorbitol carboxymethylether, and 44 mg mannitol in a sterile aqueous colloidal solution. 1
• The formulation is isotonic (osmolality 270-330 mOsm/kg), preservative-free, with pH 6-8, appearing as a black to reddish brown liquid. 1

Mechanism of Action

• The carbohydrate shell isolates bioactive iron from plasma components until the iron-carbohydrate complex enters reticuloendothelial system macrophages of the liver, spleen, and bone marrow. 1
• Iron is released from the complex within macrophage vesicles, then either enters intracellular storage pools (ferritin) or transfers to plasma transferrin for transport to erythroid precursor cells for hemoglobin incorporation. 1

Dosing and Administration

• The standard FDA-approved regimen is 510 mg administered as an intravenous infusion over at least 15 minutes, given in two divided doses separated by 3-8 days (total 1020 mg). 2, 1
• Maximum single dose is 510 mg with maximum weekly dose of 1020 mg. 2
• The original rapid injection method (17 seconds) was changed to minimum 15-minute infusion after postmarketing surveillance documented high incidence of infusion reactions with rapid administration. 2
• Studies have demonstrated safety and efficacy of 1020 mg administered as a single 30-minute infusion without serious adverse events. 2

Clinical Indications

• FDA-approved specifically for treatment of iron deficiency anemia in adult patients with chronic kidney disease. 1, 3
• Used in both non-dialysis-dependent CKD (stages 1-5) and hemodialysis-dependent CKD (stage 5D). 3, 4
• Medical necessity requires documented failure, intolerance, or contraindication to oral iron therapy before ferumoxytol is considered appropriate. 5

Efficacy

• In randomized controlled trials, two doses of ferumoxytol (510 mg each) increased mean hemoglobin by approximately 1.0 g/dL over 35 days, significantly greater than oral iron (200 mg/day for 21 days). 3, 4, 6
• In hemodialysis patients, ferumoxytol resulted in mean hemoglobin increase of 1.02 ± 1.13 g/dL versus 0.46 ± 1.06 g/dL with oral iron (p=0.0002). 6
• Twice as many ferumoxytol-treated patients achieved ≥1 g/dL hemoglobin increase compared to oral iron-treated patients. 6

Safety Profile

• The most important safety concerns are hypersensitivity reactions and hypotension, with anaphylaxis/anaphylactoid reactions reported in 0.2% of subjects and hypotension in 1.9%. 3
• Other hypersensitivity-related adverse reactions (pruritus, rash, urticaria, wheezing) occurred in 3.7% of patients. 3
• The larger carbohydrate shell size increases theoretical risk of anaphylaxis compared to some other IV iron formulations, though serious reactions remain rare. 2
• No test dose is required, unlike low-molecular-weight iron dextran. 2
• Most adverse events are mild to moderate in intensity; local injection-site reactions are the most common. 4

Important Clinical Considerations

• Ferumoxytol transiently affects diagnostic ability of MRI imaging; radiologists must be notified if MRI is planned within 8 weeks of administration. 2, 3
• Not removed by hemodialysis. 1
• Pharmacokinetic half-life is approximately 15 hours with dose-dependent, capacity-limited elimination from plasma. 1
• Do not administer to patients with iron overload. 1

Cost and Step Therapy

• Ferumoxytol costs approximately $1,963 per typical dose compared to $405 for low molecular weight iron dextran. 5
• Insurance policies typically require step therapy with lower-cost IV iron formulations (iron dextran, iron sucrose, or ferric gluconate) before ferumoxytol. 5

Generic Formulation Concerns

• FDA approved ferumoxytol generic in 2022 based on molecular identity, but expert experience suggests the generic has double the incidence of infusion reactions compared to brand, with one reported death. 2
• High molecular weight iron-carbohydrate complexes have surface chemistry differences that result in significant pharmacokinetic, pharmacodynamic, and adverse event profile variations, making true generic equivalence unlikely. 2