FDA slaps new warning label on gadolinium-based contrast agents

The FDA is requiring that gadolinium-based contrast agents (GBCAs) carry new warnings on their labels about the risk of the rare and potentially fatal skin disease, nephrogenic systemic fibrosis (NSF), if the drug is administered to certain patients with kidney disease. Since the agency issued its decision Sept. 9, the companies that manufacture and sell these agents have begun to respond to the labeling changes.

Three of the seven FDA-approved GBCAs—Magnevist (Bayer HealthCare), Omniscan (GE Healthcare) and Optimark (Covidien)—will be described as inappropriate for use among patients with acute kidney injury or chronic severe kidney disease, according to the FDA announcement. However, all GBCA labels also will now emphasize the need to screen patients to detect these types of kidney dysfunction before administration.

In late 2009, the agency suggested these three top selling GBCAs posed the greatest risk of leading to NSF. The FDA said its review of the safety of the most widely used GBCAs determined that Magnevist, Omniscan, and Optimark are associated with a greater risk than other GBCAs for NSF in certain patients with kidney disease.

GBCAs are intravenous drugs approved by the FDA for use with MRI or MR angiography (MRA) to help detect abnormalities of body organs, blood vessels and other tissues.

NSF is a condition involving the formation of excess fibrous connective tissue in the skin, joints, eyes and internal organs. Symptoms of NSF can include scaling, hardening and tightening of the skin, red or dark patches on the skin, and stiffness. NSF may lead to death, especially if it involves body organs.

“The FDA is requiring these labeling changes to enhance the safe use of gadolinium-based contrast agents, including avoidance of certain agents among patients at highest risk for nephrogenic systemic fibrosis,” said Rafel (Dwaine) Rieves, MD, director of the division of medical imaging products in the FDA’s Center for Drug Evaluation and Research.
 
In response to the changes, GE agreed to update its label with the revisions, including the contraindication for patients with chronic kidney disease, severe kidney disease or acute kidney injury. While the company said the new safety language reinforces the need for appropriate patient selection and patient management, GE noted that Omniscan has been used for more than 17 years in more than 48 million doses. "GBCAs continue to be a valuable diagnostic tool with a proven safety record," the company added in a press statement.

“Covidien is pleased the FDA has taken this important step in clarifying the appropriate use of the class of gadolinium agents,” said Herbert Neuman, MD, chief medical officer of Pharmaceuticals at Covidien. In November 2009, Covidien’s Mallinckrodt business voluntarily contraindicated the use of its Optimark in MRI procedures involving the same small group of patients with severe renal impairment. According to the Dublin-based company, Mallinckrodt’s previous label change is largely consistent with the new FDA requirements.

Also, Lantheus Medical Imaging, which distributes Ablavar (gadofosveset trisodium), a gadolinium-based MRA blood pool imaging agent, said it supports FDA's labeling changes. “We support the FDA for taking action to ensure the safe and appropriate use of gadolinium-based contrast agents, and we agree with the changes put forth by the FDA for Ablavar,” said Mark Hibberd, MD, PhD, senior medical director at Lantheus.

The other affected manufacturers have yet to respond as of press time.