Ferumoxytol

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Ferumoxytol
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rabin Bista, M.B.B.S. [2]

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Black Box Warning

WARNING:
See full prescribing information for complete Boxed 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 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

Overview

Ferumoxytol is a iron replacement product that is FDA approved for the treatment of iron deficiency anemia in adult patients with chronic kidney disease. There is a Black Box Warning for this drug as shown here. Common adverse reactions include diarrhea, nausea, dizziness, hypotension, constipation, and peripheral edema.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

  • Feraheme is indicated for the treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD)

Dosage

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, 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.

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.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Ferumoxytol in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Ferumoxytol in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

  • Safety and efficacy not established in pediatric patients

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Ferumoxytol in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Ferumoxytol in pediatric patients.

Contraindications

  • Known hypersensitivity to Feraheme or any of its components

History of allergic reaction to any intravenous iron product

Warnings

WARNING:
See full prescribing information for complete Boxed 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 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
  • Serious Hypersensitivity Reactions

Fatal and serious hypersensitivity reactions including anaphylaxis, presenting with cardiac/ cardiorespiratory arrest, clinically significant hypotension, syncope, or unresponsiveness have occurred in patients receiving Feraheme [SEE BOXED WARNING]. Other adverse reactions potentially associated with hypersensitivity have occurred (pruritus, rash, urticaria, and wheezing). These reactions have occurred following the first dose or subsequent doses in patients in whom a previous Feraheme dose was tolerated.

Patients with a history of multiple drug allergies may have a greater risk of anaphylaxis with parenteral iron products. Carefully consider the potential risks and benefits before administering Feraheme to these patients.

Only administer Feraheme when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions. Closely observe patients for signs and symptoms of hypersensitivity including monitoring of blood pressure and pulse during and after Feraheme administration for at least 30 minutes and until clinically stable following completion of each infusion [SEE ADVERSE REACTIONS (6.2)].

In clinical studies predominantly in patients with CKD, serious hypersensitivity reactions were reported in 0.2% (3/1,726) of subjects receiving Feraheme. Other adverse reactions potentially associated with hypersensitivity (e.g., pruritus, rash, urticaria or wheezing) were reported in 3.7% (63/1,726) of these subjects. In other trials excluding patients with Stages 4 and 5 CKD, moderate to severe hypersensitivity reactions were reported in 2.6% (26/1014) of patients treated with Feraheme.

In the post-marketing experience, fatal and serious anaphylactic type reactions presenting with cardiac/ cardiorespiratory arrest, clinically significant hypotension, syncope, and unresponsiveness have been reported. Elderly patients with multiple or serious co-morbidities who experience hypersensitivity reactions and/or hypotension following administration of Feraheme may have more severe outcomes [SEE BOXED WARNING, ADVERSE REACTIONS (6.2) and USE IN SPECIFIC POPULATIONS (8.5)].

5.2 Hypotension Severe adverse reactions of clinically significant hypotension have been reported. In clinical studies, hypotension was reported in 1.9% (33/1,726) of subjects, including three patients with serious hypotensive reactions. Hypotension has also been reported in the post-marketing experience [SEE ADVERSE REACTIONS FROM POST-MARKETING SPONTANEOUS REPORTS (6.2)]. Monitor patients for signs and symptoms of hypotension following each Feraheme administration [SEE DOSAGE AND ADMINISTRATION (2) and WARNINGS AND PRECAUTIONS (5.1)].

5.3 Iron Overload Excessive therapy with parenteral iron can lead to excess storage of iron with the possibility of iatrogenic hemosiderosis. Regularly monitor the hematologic response during parenteral iron therapy [SEE DOSAGE AND ADMINISTRATION (2)]. Do not administer Feraheme to patients with iron overload.

In the 24 hours following administration of Feraheme, laboratory assays may overestimate serum iron and transferrin bound iron by also measuring the iron in the Feraheme complex.

5.4 Magnetic Resonance (MR) Imaging Administration of Feraheme may transiently affect the diagnostic ability of MR imaging. Anticipated MR imaging studies should be conducted prior to the administration of Feraheme. Alteration of MR imaging studies may persist for up to 3 months following the last Feraheme dose. If MR imaging is required within 3 months after Feraheme administration, use T1- or proton density-weighted MR pulse sequences to minimize the Feraheme effects; MR imaging using T2-weighted pulse sequences should not be performed earlier than 4 weeks after the administration of Feraheme. Maximum alteration of vascular MR imaging is anticipated to be evident for 1 – 2 days following Feraheme administration [SEE CLINICAL PHARMACOLOGY (12.3)].

Feraheme will not interfere with X-ray, computed tomography (CT), positron emission tomography (PET), single photon emission computed tomography (SPECT), ultrasound or nuclear medicine imaging.

Adverse Reactions

Clinical Trials Experience

Feraheme administration may cause serious hypersensitivity reactions and hypotension [SEE WARNINGS AND PRECAUTIONS (5.1),(5.2)].

In clinical studies, 1,726 subjects were exposed to Feraheme; 1,562 of these had CKD and 164 did not have CKD. Of these subjects 46% were male and the median age was 63 years (range of 18 to 96 years).

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in practice.

6.1 Adverse Reactions in Clinical Studies Across the three randomized clinical trials [Trial 1, 2, and 3, SEE CLINICAL STUDIES (14)], a total of 605 patients were exposed to two injections of 510 mg of Feraheme and a total of 280 patients were exposed to 200 mg/day of oral iron for 21 days. 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 the randomized clinical trials are listed in Table 1. Diarrhea (4.0%), constipation (2.1%) and hypertension (1.0%) have also been reported in Feraheme-treated patients.

In clinical trials, adverse reactions leading to treatment discontinuation and occurring in ≥ 2 Feraheme-treated patients included hypotension, infusion site swelling, increased serum ferritin level, chest pain, diarrhea, dizziness, ecchymosis, pruritus, chronic renal failure, and urticaria.

Following completion of the controlled phase of the trials, 69 patients received two additional 510 mg intravenous injections of Feraheme (for a total cumulative dose of 2.04 g). Adverse reactions following this repeat Feraheme dosing were similar in character and frequency to those observed following the first two intravenous injections.

In a placebo-controlled, cross-over trial, 713 patients with CKD received a single 510 mg dose of Feraheme. Adverse reactions reported by these patients were similar in character and frequency to those observed in other clinical trials.

Postmarketing Experience

Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following serious adverse reactions have been reported from the post-marketing experience with Feraheme: fatal, life-threatening, and serious anaphylactic-type reactions, cardiac/cardiorespiratory arrest, clinically significant hypotension, syncope, unresponsiveness, loss of consciousness, tachycardia/rhythm abnormalities, angioedema, ischemic myocardial events, congestive heart failure, pulse absent, and cyanosis. These adverse reactions have usually occurred within 30 minutes after the administration of Feraheme. Reactions have occurred following the first dose or subsequent doses of Feraheme.

Drug Interactions

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

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

  • There are no studies of Feraheme in pregnant women. In animal studies, ferumoxytol caused fetal malformations and decreased fetal weights at maternally toxic doses of 6 times the estimated human daily dose. Use Feraheme during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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 during organogenesis at a maternally toxic dose of 100 mg Fe/kg/day, approximately 6 times the estimated human daily dose based on body surface area, caused a decrease in fetal weights. In rabbits, administration of ferumoxytol during organogenesis at a maternally toxic dose of 45 mg Fe/kg/day, approximately 6 times the estimated human daily dose based on body surface area, was associated with external and/or soft tissue fetal malformations and decreased fetal weights.
Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Ferumoxytol in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Ferumoxytol during labor and delivery.

Nursing Mothers

It is not known whether Feraheme is present in human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to avoid Feraheme, taking into account the importance of Feraheme to the mother and the known benefits of nursing.

Pediatric Use

The safety and effectiveness of Feraheme in pediatric patients (less than 18 years old) have not been established.

Geriatic Use

In controlled clinical trials, 330 patients ≥ 65 years of age were treated with Feraheme. No overall differences in safety and efficacy were observed between older and younger patients in these trials, but greater sensitivity of older individuals cannot be ruled out. In general, dose administration to an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients with multiple or serious co-morbidities who experience hypersensitivity reactions and/or hypotension following administration of Feraheme may have more severe outcomes. The potential risks and benefits of Feraheme administration should be carefully considered in these patients

Gender

There is no FDA guidance on the use of Ferumoxytol with respect to specific gender populations.

Race

There is no FDA guidance on the use of Ferumoxytol with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Ferumoxytol in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Ferumoxytol in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Ferumoxytol in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Ferumoxytol in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Intravenous

Monitoring

  • Closely observe patients for signs and symptoms of hypersensitivity including monitoring of blood pressure and pulse during and after Feraheme administration for at least 30 minutes and until clinically stable following completion of each infusion
  • Monitor patients for signs and symptoms of hypotension following each Feraheme administration
  • Regularly monitor the hematologic response during parenteral iron therapy

IV Compatibility

There is limited information regarding IV Compatibility of Ferumoxytol in the drug label.

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

Pharmacology

There is limited information regarding Ferumoxytol Pharmacology in the drug label.

Mechanism of Action

Structure

File:Ferumoxytol01.png
This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Ferumoxytol in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Ferumoxytol in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Ferumoxytol in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Ferumoxytol in the drug label.

How Supplied

Storage

There is limited information regarding Ferumoxytol Storage in the drug label.

Images

Drug Images

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Ferumoxytol in the drug label.

Precautions with Alcohol

  • Alcohol-Ferumoxytol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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