PRAC Recommends Suspending Marketing Authorization for Four Gadolinium Contrast Agents

Deborah Brauser

March 10, 2017

Findings of gadolinium deposits in patients who have undergone MRI body scans have led the European Medicines Agency’s (EMA's) Pharmacovigilance Risk Assessment Committee (PRAC) to recommend suspending marketing authorization for four contrast agents.

These include the linear gadolinium products gadobenic acid, gadopentetic acid, gadodiamide, and gadoversetamide. After administration of intravenous injections of these agents, "small amounts of the gadolinium they contain are deposited in the brain," reports the PRAC in a release.

Although the committee notes that there have been no signs of harm from these deposits, it is still recommending regulatory action. In addition to gadolinium showing harmful effects to tissue in nonclinical laboratory studies, there have been few data on its long-term effects on the brain.

The PRAC notes that the recommended marketing authorization suspensions "can be lifted if the respective companies provide evidence of new benefits in an identified patient group that outweigh its risk or show that their product (modified or not) does not release gadolinium significantly…or lead to its retention in tissues."

In the meantime, they are recommending the lowest possible dose of macrocyclic agents when body scan imaging needs to be enhanced, or, as needed, low doses of the linear agents gadoxetic acid (for liver scans) or the formulation of gadopentetic acid that is injected directly into joints.

The PRAC notes that of these latter two linear agents, the first "meets an important diagnostic need in patients with few alternatives" and the second has a very low concentration of gadolinium.

"Convincing Evidence"

As reported  by Medscape Medical News, this review process began on March 17, 2016, after the PRAC received a request to do so from the European Commission.

After examining studies that directly measured gadolinium deposits several months after patients' last injection with the contrast agents, the committee found "convincing evidence" of gadolinium accumulation in the brain.

"The companies concerned with this review have the right to request the PRAC to re-examine its recommendations," they report.

Once the suggestions are final, they will be sent on for the Committee for Medicinal Products for Human Use to weigh in.

Back in 2015, the US Food and Drug Administration announced it was starting its own investigation into possible health risks from repeated use of gadolinium-based contrast agents before MRI.

Last year, a study published in JAMA showed no significant link between exposure to the agents and parkinsonism.

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