The medical regulatory body of the European Union (EU) recommended four gadolinium contrast agents be pulled from the market because of concerns about gadolinium deposition in the brain.
The European Medicines Agency (EMA)—the EU’s FDA-equivalent—suspended the marketing authorizations for the four agents after a review by its Pharmacovigilance and Risk Assessment Committee (PRAC).
“Although no symptoms or diseases linked to gadolinium in the brain have been reported, the PRAC took a precautionary approach, noting that data on the long-term effects in the brain are limited,” the EMA said in a press release. “Deposition of gadolinium in other organs and tissues has been associated with rare side effects of skin plaques and nephrogenic systemic fibrosis, a scarring condition in patients with kidney impairment. Furthermore, non-clinical laboratory studies have shown that gadolinium can be harmful to tissues.”
The agents in question are gadobenic acid, gadodiamide, gadopentetic acid and gadoversetamide—all of which have a linear structure. Linear agents have an elongated molecular structure that wraps around the gadolinium ion, making them more likely to release gadolinium. Macrocyclic agents were excluded from these recommendations because they have a cage-like structure and are less likely to release gadolinium.
The issue of gadolinium deposition is a tricky one: While there’s little evidence of long-term harm, the deposition itself is concerning—especially when there’s no central authority for keeping track of gadolinium dosage over a patient’s lifetime.
According to an article published in the Journal of the American College of Radiology, detailed inter-institutional logs of gadolinium dosage should be a priority for radiology departments across the country. Products like GE Healthcare’s DoseWatch and Bayer’s Radimetrics offer contrast tracking, but they have varying levels of integration with general electronic medical record systems, so a permanent solution is still needed.
The PRAC provides a path for the marketing authorizations to be reinstated, but the barrier to re-entry will require a new weighing of patient harm vs. patient benefit.
“For those marketing authorizations recommended for suspension, the suspensions can be lifted if the respective companies provide evidence of new benefits in an identified patient group that outweigh its risks or show that their product (modified or not) does not release gadolinium significantly (dechelation) or lead to its retention in tissues,” the EMA wrote.
In any case, the PRAC’s recommendations will be sent to the Committee for Medicinal Products for Human Use, which will adopt the EMA’s opinion on the four agents. Finally, the European Commission will adopt a legally binding decision applicable in all 28 EU members and other states with varying levels of EU integration.