FDA sharpens MR contrast warning, singles out three agents as ‘inappropriate’

Three of the most popular MR contrast agents-Magnevist by Bayer Healthcare, Omniscan by GE Healthcare, and Optimark by Covidien-will soon carry labels warning that their use is “inappropriate” for patients with acute kidney injury or chronic severe kidney disease. These and other gadolinium-containing agents will also carry new warnings emphasizing the need to screen patients for kidney dysfunction that puts them at risk for nephrogenic systemic fibrosis, the rare but potentially fatal condition that led the FDA to require warning labels on these agents in 2007.

Three of the most popular MR contrast agents-Magnevist by Bayer Healthcare, Omniscan by GE Healthcare, and Optimark by Covidien-will soon carry labels warning that their use is “inappropriate” for patients with acute kidney injury or chronic severe kidney disease. These and other gadolinium-containing agents will also carry new warnings emphasizing the need to screen patients for kidney dysfunction that puts them at risk for nephrogenic systemic fibrosis, the rare but potentially fatal condition that led the FDA to require warning labels on these agents in 2007.

The new labels are expected within two months. Manufacturers are now reviewing text sent them by the FDA in early September. Dr. Dwaine Rieves, director of the FDA’s division of medical imaging products, described the text written by the FDA as a “minimum expectation” for the labeling. Manufacturers can enhance it or make alternative proposals, Rieves said, subject to FDA approval.

The FDA wrote the text based on findings presented in December 2009 by an FDA advisory committee. In its review of postmarketing reports, new animal and in vitro reports, and published reports, the committee determined that changes in the labeling were needed to enhance the safe use of gadolinium-containing contrast agents. Magnevist, Omniscan, and Optimark were singled out because the FDA determined that these agents are associated with a greater risk for NSF than others in certain patients with kidney disease.

Because the data suggest that NSF may follow the administration of any gadolinium-containing contrast agent, the wording on all labels accompanying these drugs will carry more specific details about the risks than the current warning. The new labeling will better characterize one of the high-risk groups, those with acute kidney injury, while emphasizing the importance of screening patients, Rieves said. The text will also stress the need to record the specific contrast agent administered and the dose.

“One of the particular concerns from postmarketing reports was lack of information regarding which of the GBCAs (gadolinium-based contrast agents) was actually administered to a patient, as well as the dose,” Rieves told Diagnostic Imaging in an e-mail.

Lantheus Medical Imaging, which markets the MR blood pool contrast agent Ablavar, describes the revised language as providing clearer guidance to healthcare professionals about the risk of gadolinium-based contrast agent-associated NSF in patients who are renally impaired.

In addition to the warnings being written into the labels, the FDA recommends that staff perform laboratory tests to estimate kidney function in patients who are at risk for reduced kidney function, avoid the use of gadolinium-based agents in patients suspected or known to have impaired drug elimination unless the imaging is essential and not available without contrast, monitor for signs and symptoms of NSF if a Gd-based agent is administered to a patient with acute kidney injury or chronic, severe kidney disease, and administer a Gd-based agent only once during an imaging session.