Since their introduction in 1988, Gd-based contrast agents have been used in hundreds of millions of patients.1,2 But with the emergence of rare but potentially severe side effects, efforts have been undertaken to optimize patient safety.2,3
The occurrence of NSF, a rare but potentially fatal disease, was first identified with the use of Gd-based contrast agents (GBCAs). Since then, NSF has been reported in patients with severe or end-stage renal failure.3
The European Medicines Agency (EMA) contraindicated the use of certain GBCAs in patients with severe renal impairment4 and the FDA mandated a class-label boxed warning regarding the potential for NSF for all GBCAs.5
Since 2009, the number of reports of NSF has fallen
substantially. The first decreases of NSF were recorded
in 2007 and 2008.7 This suggests the introduction of
recommendations in 2006, which include screening of
high-risk (renally impaired) patients, may have achieved the desired outcome of reducing the risk of NSF.5,7
The EMA restricted the dose of high-risk GBCAs to the
minimum recommended dose, recommending a period
of at least 7 days between injections in patients with
moderate kidney problems, and in infants up to 1 year
of age. The EMA prohibited the use of these agents in
neonates, in patients with severe kidney problems, and
in patients approaching or recently recovering from liver
The FDA updated its recommendations in 2017:
“To date, the only known adverse health effect related to
gadolinium retention is a rare condition called nephrogenic
systemic fibrosis (NSF) that occurs in a small subgroup of
patients with pre-existing kidney failure. We have also received reports of adverse events involving multiple organ systems in patients with normal kidney function. A causal association between these adverse events and gadolinium retention could not be established.”
The current recommendation from the FDA issued in
2018 maintains the 2017 guidance that:8
“Health care professionals should consider the retention characteristics of each agent when choosing a GBCA for patients who may be at higher risk for gadolinium retention (see Table 1 listing GBCAs). These patients include those requiring multiple lifetime doses, pregnant women, children, and patients with inflammatory conditions. Minimize repeated GBCA imaging studies when possible, particularly closely spaced MRI studies. However, do not avoid or defer necessary GBCA MRI scans.”
Given the current understanding of these issues, GBCAs
are still an essential tool for achieving the optimal clinical benefit from MRI use in appropriate patients, as described in guidelines.8 To meet the needs of patient populations identified in the guidelines and who may be at increased risk, there is a clinical need for new agents with a greater variety of retention characteristics that will enable HCPs to appropriately address and help reduce these risks.2
- Lancelot E. Revisiting the pharmacokinetic profiles of gadolinium-based contrast agents: differences in long-term biodistribution and excretion. Invest Radiol. 2016;51:691-700.
- Lancelot E, Raynaud JS, Desché P. Current and future MR contrast agents: seeking a better chemical stability and relaxivity for optimal safety and efficacy. Invest Radiol. 2020;55:578-588.
- Thomsen HS, Morcos SK, Almén T, et al. Nephrogenic systemic fibrosis and gadolinium- based contrast media: updated ESUR Contrast Medium Safety Committee guidelines. Eur Radiol. 2013;23:307-318.
- European Medicines Agency. Assessment report for gadolinium-containing contrast agents. https://www.ema.europa.eu/en/documents/referral/gadolinium-h-31-1097- assessment-report_en.pdf. Accessed March 30, 2022.
- U.S. Food and Drug Administration. FDA alert: gadolinium-based contrast agents for magnetic resonance imaging (marketed as Magnevist, MultiHance, Omniscan, OptiMARK, ProHance). https://www.ncbi.nlm.nih.gov/books/NBK23234/bin/FDAHP.pdf. Accessed March 14, 2022.
- European Medicines Agency. Gadolinium-containing contrast agents. https://www.ema.europa.eu/en/medicines/human/referrals/gadolinium-containing- contrast-agents-0. Accessed March 30, 2022.
- Endrikat J, Dohanish S, Schleyer N, et al. 10 years of nephrogenic systemic fibrosis: a comprehensive analysis of nephrogenic systemic fibrosis reports received by a pharmaceutical company from 2006 to 2016. Invest Radiol. 2018;53:541-550.
- U.S. Food and Drug Administration. FDA drug safety communication: FDA warns that gadolinium-based contrast agents (GBCAs) are retained in the body; requires new class warnings. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety- communication-fda-warns-gadolinium-based-contrast-agents-gbcas-are-retained-body. Accessed March 30, 2022