EU reconsiders pulling gadolinium contrast agents from market

The European Medicines Agency (EMA) will re-examine its decision to pull several gadolinium contrast agents from the European single market following requests from gadolinium producers.

The contrast agents’ marketing authorizations were revoked in March over fears of gadolinium deposition in the brain. Although no adverse neurological effects have been recorded, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) was taking a cautionary approach.

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.

Nonetheless, the committee reconsidered the ban on linear agents after gadolinium producers and imaging societies raised objections.

“While there is clear evidence that all types of [gadolinium contrast agents], both linear and macrocyclic, may result in trace amounts of gadolinium in the brain, there exists no clinical evidence that this leads to an increase in risk or harm to patients,” GE Healthcare said in a press release defending Omniscan, its MRI contrast agent. “In addition, Omniscan has a specific cardiac indication in several European Member States; removing it would limit clinical choice.”

The American College of Radiology (ACR) also made its voice heard, characterizing the amount of contrast agent remaining in the brain as insignificant.

“There is indisputable evidence that the amount of gadolinium deposited in tissues after a single [Gadolinium-Based Contrast Agent] dose is incredibly small and is detectable using only the most sensitive of medical and scientific instrumentation,” the ACR said in a statement. “Further, although gadolinium accumulation appears to be dose-dependent, there remains no evidence of cellular toxicity, nor is there credible evidence of neurologic sequelae after over 300 million worldwide human doses.”

Not all parties with a stake in gadolinium opposed the ruling, however. French pharmaceutical firm Guerbet agreed with the recommendation, even going as far as to relabel two linear contrast agents sold in the US with warnings about gadolinium deposition. The agents will continue to be available for clinical use but Guerbet is monitoring the situation closely, according to a release.

The PRAC’s re-examination of linear Gadolinium contrast agents is expected to conclude in July.