General Information

Feraheme is a superparamagnetic iron oxide nanoparticle coated with a low molecular weight semi-synthetic carbohydrate. It helps to isolate the bioactive iron from plasma components until the iron-carbohydrate complex enters the reticuloendothelial system macrophages of the liver, spleen and bone marrow. The iron is released from the iron-carbohydrate complex within vesicles in the macrophages. Iron then either enters the intracellular storage iron pool (e.g., ferritin) or is transferred to plasma transferrin for transport to erythroid precursor cells for incorporation into hemoglobin.

Feraheme is specifically indicated for the treatment of iron deficiency anemia in adult patients with chronic kidney disease.

Feraheme is supplied as a solution for intravenous injection. The recommended initial dose is a 510 mg intravenous injection followed by a second 510 mg intravenous injection 3 to 8 days later. Feraheme should be administered as an undiluted intravenous injection delivered at a rate of up to 1 mL/sec (30 mg/sec). For patients receiving hemodialysis, administer Feraheme once the blood pressure is stable and the patient has completed at least one hour of hemodialysis.

Mechanism of Action

Feraheme is a superparamagnetic iron oxide nanoparticle coated with a low molecular weight semi-synthetic carbohydrate. It helps to isolate the bioactive iron from plasma components until the iron-carbohydrate complex enters the reticuloendothelial system macrophages of the liver, spleen and bone marrow. The iron is released from the iron-carbohydrate complex within vesicles in the macrophages. Iron then either enters the intracellular storage iron pool (e.g., ferritin) or is transferred to plasma transferrin for transport to erythroid precursor cells for incorporation into hemoglobin.

Side Effects

Adverse events associated with the use of Feraheme may include, but are not limited to, the following:

• diarrhea
• nausea
• dizziness
• hypotension
• constipation
• peripheral edema

The Feraheme drug label comes with the following Black Box Warning: Fatal and serious hypersensitivity reactions including anaphylaxis have occurred in patients receiving Feraheme. Initial symptoms may include hypotension, syncope, unresponsiveness, cardiac/cardiorespiratory arrest. Only administer Feraheme as an intravenous infusion over at least 15 minutes and only when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions. Observe for signs or symptoms of hypersensitivity reactions during and for at least 30 minutes following Feraheme infusion including monitoring of blood pressure and pulse during and after Feraheme administration. Hypersensitivity reactions have occurred in patients in whom a previous Feraheme dose was tolerated.

Clinical Trial Results

The FDA approval of Feraheme was based on three randomized, open-label, controlled clinical trials. In all three trials, subjects were randomized to treatment with Feraheme, administered as two 510 mg intravenous single doses, or oral iron (ferrous fumarate), administered as a total daily dose of 200 mg elemental iron daily for 21 days. The major trial outcomes assessed the change in hemoglobin from baseline to Day 35. Trial Oneenrolled 303 subjects with non-dialysis dependent CKD; Trial Two enrolled 304 subjects with non-dialysis dependent CKD; Trial Three enrolled 230 subjects who were undergoing hemodialysis. Feraheme reached the primary endpoint with statistical significance (p<0.001) in all three trials versus oral iron.

An uncontrolled, follow-up trial was also conducted during which subjects with persistent iron deficiency anemia could receive two additional 510 mg intravenous injections of Feraheme, for a total cumulative dose of 2.04 g. Overall, 69 subjects received the additional injections of Feraheme, and on Day 35 following these additional injections, the majority of these patients (70%) experienced an increase in hemoglobin and iron parameters (TSAT and ferritin). The mean change in hemoglobin level from the retreatment baseline for patients with an increase in hemoglobin was 0.86 (± 0.68) g/dL and was 0.5 (± 0.8) g/dL for all patients.