If a patient has a gadolinium-containing contrast agent anaphylactic allergy, can they receive Feraheme?

Comment by InpharmD Researcher

There is limited evidence evaluating the safety of ferumoxytol in patients with a prior anaphylactic reaction to a gadolinium-based contrast agent (GBCA); thus, definitive conclusions regarding its use in this setting cannot be made. Feraheme (ferumoxytol) prescribing information does not list GBCA allergy as a contraindication, but contraindicates use in patients with known hypersensitivity to ferumoxytol or a history of allergic reaction to any intravenous iron product and warns that serious hypersensitivity reactions, including anaphylaxis, may occur. Available studies report a low incidence of adverse reactions with diagnostic ferumoxytol use; however, patients with prior GBCA-induced anaphylaxis were not specifically evaluated, and the only identified study, including a patient with a reported gadolinium allergy, did not describe the severity of the prior reaction or report that patient’s outcome separately.
Background

The 2026 ACR Manual on Contrast Media does not identify a prior anaphylactic reaction to a gadolinium-based contrast agent as a contraindication to ferumoxytol (Feraheme). The manual states that ferumoxytol should not be administered to patients with a history of allergic reactions to intravenous iron preparations and advises careful consideration of its risks and benefits in patients with multiple medication allergies. Because serious hypersensitivity reactions, including anaphylaxis, may occur even after previously tolerated doses, ferumoxytol should be administered in a setting with personnel and therapies immediately available to manage anaphylaxis, with monitoring during the infusion and for at least 30 minutes afterward. [1]

A 2021 meta-analysis evaluated 39 studies comprising 5,411 off-label ferumoxytol administrations for MRI in 4,336 patients. The pooled adverse-event rate was approximately 2%; 88% of reported events were mild, 11% were moderate, and 1% were severe, with one suspected anaphylactic reaction and no ferumoxytol-related deaths reported. However, none of the included studies evaluated ferumoxytol specifically in patients with a prior hypersensitivity reaction to a gadolinium-based contrast agent. Accordingly, the review provides no direct evidence establishing the safety of Feraheme in patients with previous gadolinium-based contrast agent (GBCA)-associated anaphylaxis. [2]

Background References: [1] American College of Radiology Committee on Drugs and Contrast Media. ACR Manual on Contrast Media. American College of Radiology; 2026.
[2] Ahmad F, Treanor L, McGrath TA, Walker D, McInnes MDF, Schieda N. Safety of Off-Label Use of Ferumoxtyol as a Contrast Agent for MRI: A Systematic Review and Meta-Analysis of Adverse Events. J Magn Reson Imaging. 2021;53(3):840-858. doi:10.1002/jmri.27405
Relevant Prescribing Information

CONTRAINDICATIONS [3]
Feraheme is contraindicated in patients with:
Known hypersensitivity to Feraheme or any of its components
History of allergic reaction to any intravenous iron product

WARNINGS AND PRECAUTIONS [3]
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. 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.

BOXED WARNING [3]
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.

Relevant Prescribing Information References: [3] Feraheme (ferumoxytol injection). Prescribing Information. AMAG Pharmaceuticals, Inc.; 2026.
Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question:

If a patient has a gadolinium-containing contrast agent anaphylactic allergy, can they receive Feraheme?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-3 for your response.

Multicenter Safety and Practice for Off-Label Diagnostic Use of Ferumoxytol in MRI
Design

Multicenter, open-label, nonrandomized surveillance databank

N= 3215
Objective To report multicenter safety data for off-label diagnostic ferumoxytol use
Study Groups All patients (n= 3215)
Inclusion Criteria Patients who received ferumoxytol injections for MRI between January 2003 and October 2018
Exclusion Criteria None specified
Methods The multicenter ferumoxytol MRI registry was established as an open-label nonrandomized surveillance databank. Each center monitored all ferumoxytol administrations, classified adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events, and assessed the relationship of adverse events to ferumoxytol administration. Analysis of variance was used to compare vital signs
Duration January 2003 to October 2018
Outcome Measures

Incidence of acute adverse events for diagnostic ferumoxytol injection
Baseline Characteristics   All patients (n= 3215)
Age - Neonates (≤1 month) 45 (1.4%)
Age - Infants (1 month to ≤2 years) 71 (2.2%)
Age - Children (2 years to ≤12 years) 151 (4.7%)
Age - Adolescents (12 years to ≤16 years) 44 (1.4%)
Age - Young adults (16 years to ≤39 years) 353 (11.0%)
Age - Middle-aged adults (39 years to ≤65 years) 1442 (44.9%)
Age - Older adults (>65 years) 958 (29.8%)
Sex - Male 1897 (59%)
Sex - Female 1318 (41%)
Results   All patients (n= 3215)
No serious adverse events or adverse reactions Yes
Adverse reactions possibly related to ferumoxytol 83 (1.9%)
Mild adverse reactions 75 (1.8%)
Moderate adverse reactions 8 (0.2%)
Allergic-like reactions 31
The authors suggested that while ferumoxytol is approved for use in the treatment of iron deficiency anemia, it can serve as an alternative to gadolinium-based contrast agents.
Adverse Events Diagnostic ferumoxytol use was associated with no serious adverse events. 1.9% of injections were related to adverse reactions, including hypertension, nausea, flushing, backache, pruritus, headache, and vomiting
Study Author Conclusions Diagnostic ferumoxytol use was well tolerated, associated with no serious adverse events, and implicated in few adverse reactions. Registry results indicate a positive safety profile for ferumoxytol use in MRI
Critique The study provides valuable multicenter safety data for off-label diagnostic use of ferumoxytol, showing a low incidence of adverse reactions. However, the nonrandomized design and reliance on voluntary reporting may introduce biases. The lack of a control group limits the ability to compare directly with other contrast agents. Additionally, the study did not specifically evaluate patients with prior GBCA-induced anaphylaxis. Further prospective studies are needed to confirm these findings.
Table 1 References:
[4] Nguyen KL, Yoshida T, Kathuria-Prakash N, et al. Multicenter Safety and Practice for Off-Label Diagnostic Use of Ferumoxytol in MRI. Radiology. 2019;293(3):554-564. doi:10.1148/radiol.2019190477

High-Resolution, 3-Dimensional Ferumoxytol-Enhanced Cardiovascular Magnetic Resonance Venography in Central Venous Occlusion
Design

Retrospective study

N= 52
Objective

To evaluate the diagnostic performance of 3-dimensional (3D) ferumoxytol-enhanced CMRV (FE-CMRV) for suspected central venous occlusion in patients with renal failure and to assess its clinical impact on patient management
Study Groups

All patients (n= 52)
Inclusion Criteria

Adult patients (≥18 years) with renal failure, gadolinium allergy, insufficient access for fast intravenous infusion of contrast, or need for extended-coverage pre-procedural venous mapping
Exclusion Criteria

Not specified
Methods

Fifty-two consecutive adults underwent ferumoxytol-enhanced cardiovascular magnetic resonance venography at a single institution. Ferumoxytol 4 mg/kg was diluted at least sixfold with normal saline and administered intravenously. Before April 2015, 23 patients received ferumoxytol as a bolus over 15 seconds; subsequently, 29 patients received a slow infusion at 0.5 mg/kg/min in accordance with updated FDA recommendations. Heart rate, blood pressure, and pulse oximetry were monitored continuously, and steady-state imaging of the thorax, abdomen, and pelvis was performed at least 5 minutes after infusion. Two blinded reviewers independently evaluated image quality and venous patency across 21 venous segments. Catheter venography was used as the reference standard in 14 patients, and medical records were reviewed for additional imaging, clinical management, renal function, serum iron concentrations, procedural outcomes, and adverse events. The patient with a gadolinium allergy was not analyzed separately, and the study did not report whether the prior gadolinium reaction represented anaphylaxis.
Duration

June 2013 to May 2017
Outcome Measures

Technical success of ferumoxytol-enhanced cardiovascular magnetic resonance venography; incidence of adverse events following ferumoxytol administration; stability of vital signs during imaging; diagnostic image quality; diagnostic accuracy compared with catheter venography; requirement for additional imaging before clinical management decisions; changes in serum iron concentrations, when measured
Baseline Characteristics  

All patients (n= 52)
Female

23 (44%)
Age, median years (IQR)

47 (32–61)
CKD

44 (85%)
Hemodialysis

22 (42%)
Peritoneal dialysis

1 (2%)
No dialysis

29 (56%)
Transplant

13 (25%)

CKD stage

Stage 5

Stage 4

Stage 3

Stage 2

Stage 1

 

25 (48%)

9 (17%)

8 (15%)

1 (2%)

1 (2%)
AKI

4 (8%)

Comorbidities

Diabetes mellitus

Diabetic nephropathy

Hypertension

Heart failure

 

17 (33%)

5 (10%)

33 (63%)

6 (12%)

Abbreviations: IQR, interquartile range; CKD, chronic kidney disease; AKI, acute kidney injury.
Results

Among 52 patients who underwent ferumoxytol-enhanced cardiovascular magnetic resonance venography, including 1 patient with a reported gadolinium allergy, all examinations were technically successful, and no adverse events occurred; vital signs remained stable throughout imaging.

Diagnostic-quality images were obtained for 1,033 of 1,038 venous segments (99.5%), and final diagnostic accuracy compared with catheter venography was 100% after senior review.

No patient required additional imaging before a clinical management decision, and serum iron concentrations did not significantly change among the 3 patients with paired measurements (p= 0.65).

Outcomes were not reported separately for the patient with gadolinium allergy, and the nature or severity of the prior reaction, including whether it represented anaphylaxis, was not described.
Adverse Events

No adverse events occurred following FE-CMRV or catheter venography. Vital signs remained stable throughout the course of the FE-CMRV and catheter venography exams.
Study Author Conclusions

3D FE-CMRV is a practical, accurate, and robust technique for high-resolution mapping of central thoracic, abdominal, and pelvic veins and can be used to inform image-guided therapy. It may play a pivotal role in the care of patients in whom conventional contrast agents may be contraindicated or ineffective.
Critique

This study provides limited direct evidence because only one patient received ferumoxytol due to a gadolinium allergy, and neither the specific gadolinium agent, reaction phenotype, severity, nor individual ferumoxytol outcome was reported. Although the absence of adverse events in the overall cohort is reassuring, the study cannot establish the safety of Feraheme specifically in patients with prior gadolinium-induced anaphylaxis or determine whether such an allergy increases the risk of ferumoxytol hypersensitivity.
Table 2 References:
[5] Shahrouki P, Moriarty JM, Khan SN, et al. High resolution, 3-dimensional Ferumoxytol-enhanced cardiovascular magnetic resonance venography in central venous occlusion. J Cardiovasc Magn Reson. 2019;21(1):17. Published 2019 Mar 11. doi:10.1186/s12968-019-0528-5

 

What Does the Boxed Warning Tell Us? Safe Practice of Using Ferumoxytol as an MRI Contrast Agent
Design

Retrospective, single-center study

N= 331
Objective To provide information regarding ferumoxytol safety as an imaging agent in a single center and to assess how the Feraheme label change may affect this potential, currently off-label indication
Study Groups All patients (n= 331)
Inclusion Criteria Patients with various CNS pathologies enrolled in institutional review board–approved imaging studies
Exclusion Criteria Not specified
Methods Ferumoxytol was administered as multiple rapid bolus injections during MR imaging. Patients were evaluated for adverse events after each injection, with blood pressure, pulse, and oxygen saturation recorded before and after each injection. Patients were observed for at least 30 minutes post-administration. Data on adverse events were recorded according to CTCAE v3.0 or v4.0
Duration June 2004 to December 2015
Outcome Measures Frequency of ferumoxytol-related adverse events 
Baseline Characteristics   All patients (n= 331)
Average age, years  51.08 ± 16.82
Female-male ratio 1:1.33
Results   All infusions (n= 671) % of Infusions
Grade 1-3 adverse events 71 10.6%
Adverse events within 48 hours 58 8.6%
Hypertension 16 2.38%
Nausea 11 1.64%
Diarrhea 7 1.04%
Headache 7 1.04%
Adverse Events No anaphylactic, life-threatening, or fatal adverse events were recorded. The overall proportion of ferumoxytol-related grade 1–3 adverse events was 10.6%, including hypertension (2.38%), nausea (1.64%), diarrhea (1.04%), and headache (1.04%). History of 1 or 2 allergies was associated with an increased risk of adverse events (14.61% versus 7.51%; p= 0.007)
Study Author Conclusions

The frequency of mild ferumoxytol-related adverse events was comparable with literature results, and no serious adverse event was recorded. Although the recommendations in the boxed warning should be followed, serious adverse events appear to be rare, and with proper precautions, ferumoxytol may be a valuable MR imaging agent.
Critique

The study provides valuable safety data on the use of ferumoxytol as an MRI contrast agent, showing no serious adverse events. However, the retrospective design and single-center setting may limit the generalizability of the findings. The study's sample size, while the largest reported in a single center, may still be too low to evaluate the frequency of rare, but serious hypersensitivity reactions. Additionally, the study does not directly document successful administration in a patient with confirmed prior gadolinium-induced anaphylaxis.
Table 3 References:
[6] Varallyay CG, Toth GB, Fu R, et al. What does the boxed warning tell us? Safe practice of using ferumoxytol as an MRI contrast agent. AJNR Am J Neuroradiol. 2017;38(7):1297-1302. doi:10.3174/ajnr.A5188.