Kim-Lien Nguyen1,2, Takegawa Yoshida1,3, Isidro B Salusky4, Peng Hu1,3, and J. Paul Finn1,3
1Diagnostic Cardiovascular Imaging Laboratory, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States, 2Division of Cardiology, David Geffen School of Medicine at UCLA and VA Greater Los Angeles Healthcare System, Los Angeles, CA, United States, 3Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 4Department of Pediatric Nephrology, David Geffen School of Medicine at UCLA
Synopsis
Recent
concerns about gadolinium deposition in biologic tissues and discontinuation of
gadofosveset trisodium have created increased interest in the off-label use of
ferumoxytol as an MRI contrast agent. Limited safety data relating to the
diagnostic use of ferumoxytol are available.
We summarize our safety experience with ferumoxytol as an alternative
MRI contrast agent in 285 unique patients (314 injections) with all levels of
renal function.
PURPOSE
Concerns regarding
gadolinium deposition in biologic tissues and nephrogenic systemic fibrosis
have spurred interests in evaluating alternative contrast agents for magnetic
resonance imaging (MRI)1-2. Although FDA-approved as an intravenous
medication for the treatment of adults with anemia secondary to chronic renal
disease, ferumoxytol’s unique physiochemical properties and pharmacokinetics
can be leveraged for use as a contrast agent in MRI. The implications are
substantial, particularly in severe renal impairment where gadolinium
administration may not be suitable3. While relative safety has been
demonstrated for therapeutic use, post-marketing FDA adverse event case reports
led to a Black Box warning in 20154. To date, limited safety data
are available on the diagnostic use of ferumoxytol5-7 despite its
potential to transform the practice of MRI3. We aim to summarize our
single-center safety experience with the off label use of ferumoxytol for MRI
and to compare the effects of ferumoxytol on monitored physiologic indices in
patients under anesthesia with those of gadofosveset trisodium. Materials and methods
Consecutive
patients who underwent ferumoxytol-enhanced (FE) MRI exams between 2013 and
2016 were included. Both acute and
short-term safety were assessed. Safety monitoring protocols were in place. Adverse
events (AEs) were classified according to the Common Terminology Criteria for
Adverse Events v4.0 by the attending physician. Predominant indications
included: vascular (n=97), congenital heart disease (n=73), transplant (n=37),
transcatheter valve (n=25), and cancer imaging (n=15). In a subgroup of
patients examined under general anesthesia, recording of blood pressure, heart rate,
oxygen saturation and end-tidal CO2 was performed. For comparison, a comparable group of patients
(n=23) who underwent gadofosveset-enhanced (GE) MRI under anesthesia with
similar monitoring was also analyzed.Results
Of 285 unique patients (169 adults and 116
children; 314 injections), ages 2 days to 94 years, who underwent FE-MRI, 236
patients had at least Stage 2 renal impairment. No ferumoxytol-related severe, life threatening, or fatal AEs
occurred acutely or at short-term follow-up (18.7±10.4 months). Median creatinine was 1.7
(IQR 0.6-2.7) mg/dL; maximum creatinine 16 mg/dL. Two
patients developed ferumoxytol-related nausea,
which was classified as a mild AE. In both the ferumoxytol and gadofosveset
groups who had anesthesia, no AEs occurred.
Between group (FE-MRI vs GE-MRI) and within group (FE-MRI) variations
of physiologic indices were not statistically different (p>0.05). No
significant change in blood pressure or heart rate (p>0.05) was noted
between slow infusion of ferumoxytol (n=169) vs bolus injection (n=145)
(p>0.05). Twenty-eight patients had at least 2 repeated exams. Five patients
had three or more FE-MRI exams.Conclusions
In our single center experience encompassing 285
unique patients, of whom 236 had at least Stage 2 chronic renal disease, no
serious acute or short-term AEs occurred with the diagnostic use of ferumoxytol.
Based on our experience, ferumoxytol is a safe alternative to gadolinium-based
MRI applications. However, because of the modest population in our single
center study, firm conclusions cannot be drawn about the generalizability of
our results and thus vigilance and monitoring are recommended to mitigate
potential rare adverse reactions.Acknowledgements
No acknowledgement found.References
1. US Food and Drug Administration. FDA Drug Safety
Communication: FDA evaluating the risk of brain deposits with repeated use of
gadolinium-based contrast agents for magnetic resonance imaging (MRI). Accessed
September 1, 2015. http://www.fda.gov/Drugs/DrugSafety/ucm455386.htm.
2. US Food and Drug Administration. FDA Drug Safety
Communication: New warnings for using gadolinium-based contrast agents in
patients with kidney dysfunction. 2010. Accessed January 27, 2016. http://www.fda.gov/Drugs/DrugSafety/ucm223966.htm
3. Finn JP, Nguyen KL, Han F, Zhou Z, Salusky I, Ayad I, Hu P.
Cardiovascular MRI with ferumoxytol. Clinical Radiology. 2016; 71(8):796-806.
4. US Food and Drug Administration. FDA Drug Safety
Communication: FDA strengthens warnings and changes prescribing instructions to
decrease the risk of serious allergic reactions with anemia drug Feraheme
(ferumoxytol). 2015. Accessed March 30, 2015. http://www.fda.gov/Drugs/DrugSafety/ucm440138.htm
5.
Muehe AM, Feng D, von Eyben
R, Luna-Fineman S, Link MP, Muthig T, Huddleston AE, Neuwelt EA and
Daldrup-Link HE. Safety Report of Ferumoxytol for Magnetic Resonance Imaging in
Children and Young Adults. Invest Radiol.
2016;51:221-7.
6. Ning P, Zucker EJ, Wong P and Vasanawala SS. Hemodynamic
safety and efficacy of ferumoxytol as an intravenous contrast agents in pediatric
patients and young adults. Magnetic
resonance imaging. 2016;34:152-8.
7. Nguyen KL, Yoshida T, Han F, Ayad I, Reemtsen BL, Salusky IB,
Satou GM, Hu P, Finn JP. MRI with ferumoxytol: a single center experience of
safety across the age spectrum. J Magn Reson Imaging. 2016 Aug 2. Epub ahead of
print.