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].
Feraheme is contraindicated in patients with:
The following serious adverse reactions are described elsewhere in the labeling:
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),. 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), , 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 leading to treatment discontinuation and occurring in ≥ 2 Feraheme-treated patients included hypersensitivity (0.6%), hypotension (0.3%), and rash (0.2%).
In addition, a total of 634 subjects enrolled in and completed participation in a Phase 3 open label extension study. Of these, 337 subjects met IDA treatment criteria and received Feraheme. Adverse reactions following this repeat Feraheme dosing were generally similar in type and frequency to those observed after the first two intravenous injections.
Across three randomized clinical trials in patients with IDA and CKD (CKD Trials 1, 2, and 3), , 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 CKD randomized clinical trials are listed in Table 2. Diarrhea (4%), constipation (2.1%) and hypertension (1%) have also been reported in Feraheme-treated patients.
Table 2: Adverse Reactions to Feraheme Reported in
≥1% of Patients with IDA and CKD Trials 1, 2 and 3
| Adverse Reactions | Feraheme 2 x 510 mg (n = 605) % |
Oral Iron (n = 280) % |
| Nausea | 3.1 | 7.5 |
| Dizziness | 2.6 | 1.8 |
| Hypotension | 2.5 | 0.4 |
| Peripheral Edema | 2 | 3.2 |
| Headache | 1.8 | 2.1 |
| Edema | 1.5 | 1.4 |
| Vomiting | 1.5 | 5 |
| Abdominal Pain | 1.3 | 1.4 |
| Chest Pain | 1.3 | 0.7 |
| Cough | 1.3 | 1.4 |
| Pruritus | 1.2 | 0.4 |
| Pyrexia | 1 | 0.7 |
| Back Pain | 1 | 0 |
| Muscle Spasms | 1 | 1.4 |
| Dyspnea | 1 | 1.1 |
| Rash | 1 | 0.4 |
In these clinical trials in patients with IDA and CKD, adverse reactions leading to treatment discontinuation and occurring in ≥ 2 Feraheme-treated patients included hypotension (0.4%), chest pain (0.3%), and dizziness (0.3%).
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.
Postmarketing ExperienceBecause 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.
Feraheme is indicated for the treatment of iron deficiency anemia (IDA) in adult patients:
In a randomized, positive-and placebo-controlled, parallel-group study, healthy subjects received a supratherapeutic regimen of Feraheme (1.02 g given as two 510 mg doses within 24 hours), placebo or a single dose of 400 mg moxifloxacin (positive control). Results demonstrated no effect of Feraheme on QT interval durations. No clinically meaningful effect of Feraheme on heart rate was observed.
The pharmacokinetic (PK) behavior of Feraheme has been examined in healthy subjects and in patients with CKD stage 5D on hemodialysis. Feraheme exhibited dose-dependent, capacity-limited elimination from plasma with a half-life of approximately 15 hours in humans. The clearance (CL) was decreased by increasing the dose of Feraheme. Volume of distribution (Vd) was consistent with plasma volume, and the mean maximum observed plasma concentration (Cmax) and terminal half-life (t½) values increased with dose. The estimated values of CL and Vd following two 510 mg doses of Feraheme administered intravenously within 24 hours were 69.1 mL/hr and 3.16 L, respectively. The Cmax and time of maximum concentration (tmax) were 206 mcg/mL and 0.32 hr, respectively. Rate of infusion had no influence on Feraheme PK parameters. No gender differences in Feraheme PK parameters were observed. Feraheme is not removed by hemodialysis.
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.
Feraheme Injection is available in single-dose vials. Each vial contains 510 mg of elemental iron in 17 mL (30 mg per mL).
Storage And HandlingFeraheme 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 |
Store at 20° to 25°C (68° to 77°F). Excursions permitted to 15° – 30°C (59° – 86°F).
Distributed by: AMAG Pharmaceuticals, Inc. Waltham, MA 02451. Revised: Feb 2018
Included as part of the PRECAUTIONS section.
PRECAUTIONS Serious Hypersensitivity ReactionsFatal and serious hypersensitivity reactions including anaphylaxis, presenting with cardiac/ cardiorespiratory arrest, clinically significant hypotension, syncope, or unresponsiveness have occurred in patients receiving Feraheme. 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.
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.
HypotensionSevere 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. Monitor patients for signs and symptoms of hypotension following each Feraheme administration.
Iron OverloadExcessive 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. 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.
Magnetic Resonance (MR) ImagingAdministration 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.
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.
Patient Counseling InformationRefer patients to the FDA approved Patient Package Insert.
Prior to Feraheme administration:
Ferumoxytol was not tested for carcinogenic effects. In standard genotoxicity tests, ferumoxytol showed no evidence of mutagenic activity in an in vitro Ames test or clastogenic activity in either an in vitro chromosomal aberration assay or an in vivo micronucleus assay.
No adverse effects on fertility or general reproductive performance were noted in animal studies. Ferumoxytol had no effect on male or female fertility or general reproductive function in rats.
Use In Specific Populations Pregnancy Pregnancy Category CThere 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.
Nursing MothersIt 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 UseThe safety and effectiveness of Feraheme in pediatric patients (less than 18 years old) have not been established.
Geriatric UseIn 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.
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 following serious adverse reactions are described elsewhere in the labeling:
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),. 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), , 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 leading to treatment discontinuation and occurring in ≥ 2 Feraheme-treated patients included hypersensitivity (0.6%), hypotension (0.3%), and rash (0.2%).
In addition, a total of 634 subjects enrolled in and completed participation in a Phase 3 open label extension study. Of these, 337 subjects met IDA treatment criteria and received Feraheme. Adverse reactions following this repeat Feraheme dosing were generally similar in type and frequency to those observed after the first two intravenous injections.
Across three randomized clinical trials in patients with IDA and CKD (CKD Trials 1, 2, and 3), , 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 CKD randomized clinical trials are listed in Table 2. Diarrhea (4%), constipation (2.1%) and hypertension (1%) have also been reported in Feraheme-treated patients.
Table 2: Adverse Reactions to Feraheme Reported in
≥1% of Patients with IDA and CKD Trials 1, 2 and 3
| Adverse Reactions | Feraheme 2 x 510 mg (n = 605) % |
Oral Iron (n = 280) % |
| Nausea | 3.1 | 7.5 |
| Dizziness | 2.6 | 1.8 |
| Hypotension | 2.5 | 0.4 |
| Peripheral Edema | 2 | 3.2 |
| Headache | 1.8 | 2.1 |
| Edema | 1.5 | 1.4 |
| Vomiting | 1.5 | 5 |
| Abdominal Pain | 1.3 | 1.4 |
| Chest Pain | 1.3 | 0.7 |
| Cough | 1.3 | 1.4 |
| Pruritus | 1.2 | 0.4 |
| Pyrexia | 1 | 0.7 |
| Back Pain | 1 | 0 |
| Muscle Spasms | 1 | 1.4 |
| Dyspnea | 1 | 1.1 |
| Rash | 1 | 0.4 |
In these clinical trials in patients with IDA and CKD, adverse reactions leading to treatment discontinuation and occurring in ≥ 2 Feraheme-treated patients included hypotension (0.4%), chest pain (0.3%), and dizziness (0.3%).
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.
Postmarketing ExperienceBecause 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 INTERACTIONSDrug-drug interaction studies with Feraheme were not conducted. Feraheme may reduce the absorption of concomitantly administered oral iron preparations.
