Ferumoxytol

FDA Drug Information • Also known as: Ferabright, Feraheme, Ferumoxytol

Brand Names: Ferabright, Feraheme, Ferumoxytol
Dosage Form: POWDER
Product Type: BULK INGREDIENT

⚠ Boxed Warning (Black Box)

WARNING: RISK FOR SERIOUS HYPERSENSITIVITY/ANAPHYLAXIS REACTIONS 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. [ see Warnings and Precautions (5.1) ].

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 [ see Warnings and Precautions (5.1) ].

Hypersensitivity reactions have occurred in patients in whom a previous Feraheme dose was tolerated [ see Warnings and Precautions (5.1) ]. WARNING: RISK FOR SERIOUS HYPERSENSITIVITY/ANAPHYLAXIS REACTIONS See full prescribing information for complete boxed warning . Fatal and serious hypersensitivity reactions including anaphylaxis have occurred in patients receiving Feraheme. Initial symptoms may include hypotension, syncope, unresponsiveness, cardiac/cardiorespiratory arrest.

Hypersensitivity reactions have occurred in patients in whom a previous Feraheme dose was tolerated. ( 5.1 )

Description

11 DESCRIPTION Feraheme is an iron replacement product containing ferumoxytol for intravenous infusion. Ferumoxytol is a non-stoichiometric magnetite (superparamagnetic iron oxide) coated with polyglucose sorbitol carboxymethylether. The overall colloidal particle size is 17-31 nm in diameter. The chemical formula of Feraheme is Fe 5874 O 8752 -C 11719 H 18682 O 9933 Na 414 with an apparent molecular weight of 750 kDa. Feraheme Injection is a sterile aqueous colloidal product that is formulated with mannitol. It is a black to reddish brown liquid, and is provided in single-dose vials containing 510 mg of elemental iron. Each mL of the sterile colloidal solution of Feraheme Injection contains 30 mg of elemental iron, 30 mg polyglucose sorbitol carboxymethylether, and 44 mg of mannitol. The formulation is isotonic with an osmolality of 270-330 mOsm/kg. The product contains no preservatives, and has a pH of 6 to 8.

What Is Ferumoxytol Used For?

1 INDICATIONS AND USAGE Feraheme is indicated for the treatment of iron deficiency anemia (IDA) in adult patients:

who have intolerance to oral iron or have had unsatisfactory response to oral iron or

who have chronic kidney disease (CKD). Feraheme is an iron replacement product indicated for the treatment of iron deficiency anemia (IDA) in adult patients:

who have intolerance to oral iron or have had unsatisfactory response to oral iron ( 1 ) or

who have chronic kidney disease (CKD). ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION The recommended dose of Feraheme is an initial 510 mg dose followed by a second 510 mg dose 3 to 8 days later. Administer Feraheme as an intravenous infusion in 50-200 mL 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP over at least 15 minutes. Administer while the patient is in a reclined or semi-reclined position. Feraheme does not contain antimicrobial preservatives. Discard unused portion. Feraheme, when added to intravenous infusion bags containing either 0.9% Sodium Chloride Injection, USP (normal saline), or 5% Dextrose Injection, USP, at concentrations of 2-8 mg elemental iron per mL, should be used immediately but may be stored at controlled room temperature (25°C ± 2°C) for up to 4 hours or refrigerated (2-8° C) for up to 48 hours. The dosage is expressed in terms of mg of elemental iron, with each mL of Feraheme containing 30 mg of elemental iron. Evaluate the hematologic response (hemoglobin, ferritin, iron and transferrin saturation) at least one month following the second Feraheme infusion. The recommended Feraheme dose may be readministered to patients with persistent or recurrent iron deficiency anemia. For patients receiving hemodialysis, administer Feraheme once the blood pressure is stable and the patient has completed at least one hour of hemodialysis. Monitor for signs and symptoms of hypotension following each Feraheme infusion. Allow at least 30 minutes between administration of Feraheme and administration of other medications that could potentially cause serious hypersensitivity reactions and/or hypotension, such as chemotherapeutic agents or monoclonal antibodies. Inspect parenteral drug products visually for the absence of particulate matter and discoloration prior to administration.

The recommended dose of Feraheme is an initial 510 mg dose followed by a second 510 mg dose 3 to 8 days later. ( 2 )

Administer Feraheme as an intravenous infusion in 50-200 mL 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP over at least 15 minutes ( 2 )

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling:

Serious Hypersensitivity Reactions [ see Warnings and Precautions ( 5.1 ) ]

Hypotension [ see Warnings and Precautions ( 5.2 ) ]

Iron Overload [ see Warnings and Precautions ( 5.3 ) ]

Magnetic Resonance (MR) Imaging Test Interference [ see Warnings and Precautions ( 5.4 ) ] The most common adverse reactions (≥ 2%) are diarrhea, headache, nausea, dizziness, hypotension, constipation, and peripheral edema. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS with Feraheme, contact AMAG Pharmaceuticals, Inc. at 1-877-411-2510, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical studies, 3,968 subjects were exposed to Feraheme. Of these subjects 31% were male and the median age was 54 years (range of 18 to 96 years). The data described below reflect exposure to Feraheme in 997 patients exposed to a 1.02 g course of ferumoxytol administered as two 510 mg intravenous (IV) doses: 992 subjects (99.5%) received at least 1 complete dose of ferumoxytol and 946 subjects (94.9%) received 2 complete doses. The mean cumulative IV Iron exposure was 993.80 ±119.085 mg. The safety of Feraheme was studied in a randomized, multicenter, double-blind clinical trial in patients with IDA (IDA Trial 3), [ see Clinical Studies ( 14.1 ) ]. In this trial, patients were randomized to two intravenous infusions of 510 mg (1.02 g) of Feraheme (n=997), or two intravenous infusions of 750 mg (1.500 g) of ferric carboxymaltose (FCM) (n=1000). Both intravenous irons were infused over a period of at least 15 minutes. Most patients received their second infusion of Feraheme and FCM 7(+1) days after Dose 1. The mean (SD) age of the study population (N=1997) was 55.2 (17.16) years. The majority of patients were female (76.1%), white (71.4%) and non-Hispanic (81.8%). The mean (SD) hemoglobin at baseline for all patients was 10.4 (1.5) g/dl. Serious adverse events were reported in 3.6% (71/1997) of ferumoxytol- and FCM- treated patients. The most common (≥2 subjects) serious AEs reported in Feraheme-treated patients were syncope, gastroenteritis, seizure, pneumonia, hemorrhagic anemia, and acute kidney injury. In FCM-treated patients the most common (≥2 subjects) serious AEs were syncope, cardiac failure congestive, angina pectoris, and atrial fibrillation. Adverse reactions related to Feraheme and reported by ≥1% of Feraheme-treated patients in IDA Trial 3 are listed in Table 1 . Table 1: Adverse Reactions to Feraheme Reported in ≥1% of IDA Patients in IDA Trial 3 Adverse Reactions Feraheme 2 x 510 mg (N = 997) % Ferric Carboxymaltose 2 x 750 mg (N = 1000) % Headache 3.4 3.1 Nausea 1.8 3.4 Dizziness 1.5 1.6 Fatigue 1.5 1.2 Diarrhea 1 0.8 Back Pain 1 0.4 In IDA Trial 3, adverse reactions leading to treatment discontinuation and occurring in ≥ 2 Feraheme-treated patients included arthralgia (0.3%), dyspnea (0.3%), flushing (0.2%), chest discomfort (0.2%), chest pain (0.2%), nausea (0.2%), back pain (0.2%), dizziness (0.2%) and headache (0.2%). Across two clinical trials in patients with IDA (IDA Trial 1 and 2), [ see Clinical Studies ( 14.1 ) ], patients were randomized to: two injections (rapid intravenous injection - prior method of administration no longer approved) of 510 mg of Feraheme (n=1,014), placebo (n=200), or five injections/infusions of 200 mg of iron sucrose (n=199). Most patients received their second Feraheme injection 3 to 8 days after the first injection. Adverse reactions related to Feraheme and reported by ≥ 1% of Feraheme-treated patients in these trials were similar to those seen in Trial 3. In Trials 1 and 2, adverse reactions...

Drug Interactions

7 DRUG INTERACTIONS Drug-drug interaction studies with Feraheme were not conducted. Feraheme may reduce the absorption of concomitantly administered oral iron preparations.

Contraindications

4 CONTRAINDICATIONS Feraheme is contraindicated in patients with:

Known hypersensitivity to Feraheme or any of its components [ see Warnings and Precautions ( 5.1 ) ]

History of allergic reaction to any intravenous iron product [ see Warnings and Precautions ( 5.1 ) ]

Known hypersensitivity to Feraheme or any of its components. ( 4 )

History of allergic reaction to any intravenous iron product. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Limited available data with ferumoxytol use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. There are risks to the mother and fetus associated with untreated iron deficiency anemia (IDA) in pregnancy as well as risks to the fetus associated with maternal severe hypersensitivity reactions ( see Clinical Considerations ). In animal studies, administration of ferumoxytol to pregnant rabbits during organogenesis caused adverse developmental outcomes including fetal malformations and decreased fetal weights at maternally toxic doses of 6 times the estimated human daily dose. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Untreated iron deficiency anemia (IDA) in pregnancy is associated with adverse maternal outcomes such as post-partum anemia. Adverse pregnancy outcomes associated with IDA include increased risk for preterm delivery and low birth weight. Fetal/Neonatal adverse reactions Severe adverse reactions including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as Feraheme) which may cause fetal bradycardia, especially during the second and third trimester. Data Animal Data Administration of ferumoxytol during organogenesis, at doses of 31.6 mg Fe/kg/day in rats and 16.5 mg Fe/kg/day in rabbits, did not result in maternal or fetal effects. These doses are approximately 2 times the estimated human daily dose based on body surface area. In rats, administration of ferumoxytol...

Overdosage

10 OVERDOSAGE Limited data are available regarding overdosage of Feraheme in humans. Excessive dosages of Feraheme may lead to accumulation of iron in storage sites potentially leading to hemosiderosis. Do not administer Feraheme to patients with iron overload [ Warnings and Precautions (5.3) ]. Feraheme is not removed by hemodialysis.

How Supplied

16.1 How Supplied Feraheme is available in single-dose vials in the following package sizes ( Table 6 ). Table 6: Feraheme Packaging Description NDC Code Dose / Total volume per vial Vials / Carton NDC 59338-775-01 510 mg/ 17 mL 1 NDC 59338-775-10 510 mg/ 17 mL 10

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.