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

Abstract

Background and Purpose Despite the label change and FDA’s boxed warning added to the Feraheme® (ferumoxytol, AMAG Pharmaceuticals, Waltham, MA) label in March 2015, radiologists have shown increasing interest in using ferumoxytol as an MRI contrast agent as a supplement or alternative to gadolinium. The goals of this study are to provide information regarding ferumoxytol safety as an imaging agent in a single center, and to assess how Feraheme® label change may affect this potential, currently off label indication. Materials and Methods This retrospective study evaluated the overall frequency of ferumoxytol related adverse events (AEs) when used for CNS MRI. Subjects with various CNS pathologies were enrolled in Institutional Review Board approved imaging studies. Ferumoxytol was administered as multiple rapid bolus injections. The risk of AEs was correlated with demographic data/medical history. Results Safety of 671 ferumoxytol enhanced MR studies in 331 subjects was analyzed. No anaphylaxis, life-threating or fatal (grade 4 or 5) AE was recorded. The overall proportion of ferumoxytol related grade 1–3 AE was 10.6% (8.6% occurring within 48h), including hypertension (2.38%), nausea (1.64%), diarrhea (1.04%) and headache (1.04%). History of one or two allergies was associated with increased risk of AE (14.61% vs. no allergies of 7.51%, p=0.0069). Conclusion The frequency of mild ferumoxytol related AE was comparable with literature results, and no serious AE was recorded. While the recommendations in the boxed warning should be followed, serious AE appear to be rare events and with proper precautions ferumoxytol may be a valuable MRI agent.

Pseudoprogression of brain tumors

“…Since 2015, ferumoxytol carries an FDA warning, which recommends slow (over 15 minutes) infusion in diluted form to avoid anaphylaxis. A recent publication of 671 cases receiving 3 ml/sec bolus injections reported around 10% adverse reactions (up to 15% for allergy sufferers) but without any life‐threatening events identified …”

Measurement of microvascular cerebral blood volume changes over the cardiac cycle with ferumoxytol‐enhanced T2* MRI

“…Ferumoxytol is Food and Drug Administration‐approved for the treatment of anemia. It is not contraindicated in patients with renal failure, and although bolus injection of ferumoxytol is currently not recommended, it has a growing safety record with slow infusion . Ferumoxytol offers the advantage of strong T 1 and shortening effects and at typical doses and clinical field strengths, ferumoxytol effects are substantially higher than available gadolinium‐based contrast agents (GBCA) .…”

Comparison of ferumoxytol‐based cerebral blood volume estimates using quantitative R1 and relaxometry

“…In 2015, the U.S. Food and Drug Administration (FDA) released a Safety Communication announcement strengthening warnings regarding the use and prescription of ferumoxytol (Feraheme) over concerns of potentially fatal allergic reactions. However, more recent studies have shown that serious adverse events are rare, and with proper precautions, ferumoxytol may be a valuable contrast agent (29)(30)(31)(32)(33).…”