FDA: New Class Warning for All Gadolinium-Based Contrast Agents

New class warning and other safety measures for all gadolinium-based contrast agents
New class warning and other safety measures for all gadolinium-based contrast agents

The Food and Drug Administration (FDA) announced a new class warning and safety measures that will be required to appear in the labeling for gadolinium-based contrast agents (GBCAs) used in magnetic resonance imaging (MRI).

As an update to the May 2017 safety communication regarding gadolinium retention in the body, the FDA has concluded that the benefit of all approved GBCAs "continues to outweigh any potential risks." The remaining gadolinium in areas such as the brain has not been directly associated with adverse effects in patients with normal kidney function. 

The FDA is requiring, however, some action steps to warn clinicians and patients about gadolinium retention after an MRI when using GBCAs. A new patient Medication Guide will be required that every patient will be asked to read prior to being administered a GBCA. Also, manufacturers will be required to perform human and animal studies to further assess the safety of these contrast agents. For all GBCAs, the FDA is requiring specific updates to the following drug labeling sections: Warnings and Precautions, Adverse Reactions, Pregnancy, Clinical Pharmacology, and Patient Instructions.

GBCAs are injected to improve visualization of internal organs, blood vessels, and tissues during an MRI, which helps in diagnosing certain conditions. Although they are primarily renally eliminated, trace amounts may remain in the body for a long-term period. Of the two types of GBCAs—linear and macrocyclic—the linear GBCAs have greater and longer retention compared to macrocyclic GBCAs. Specifically, gadolinium levels retained in the body are higher after receiving Omniscan (gadodiamide) or OptiMARK (gadoversetamide) compared with Eovist (gadoxetate disodium), Magnevist (gadopentetate dimeglumine), or MultiHance (gadobenate dimeglumine). 

The lowest levels of retained gadolinium were associated with Dotarem (gadoterate meglumine), Gadavist (gadobutrol), and ProHance (gadoteridol). 

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When choosing a GBCA for a patient, the healthcare professional should consider the retention characteristics of each agent especially for patients who are at higher risk for retention. Patients at risk may include pregnant women, those requiring multiple lifetime doses, children, and patients with inflammatory conditions. While the repeated imaging studies should be kept to a minimum (particularly closely spaced MRIs), the FDA cautions to not avoid or delay necessary GBCA MRI scans. 

The only established adverse effect associated with gadolinium retention is nephrogenic systemic fibrosis (NSF), a rare condition occurring in patients with pre-existing renal failure; a causal relationship has not been established. The Agency is continuing to evaluate health risks associated with retained gadolinium and will update the public as new data becomes available.

For more information visit FDA.gov.