The U.S. Food & Drug Administration (FDA) is seeking label changes for gadolinium contrast dyes after determining that three – Bayer Healthcare’s Magnevist, GE Healthcare’s Omniscan,  and Covidien ‘s  OptiMARK -carry a higher risk of nephrogenic systemic fibrosis (NSF) than others.

According to documents released yesterday by the FDA,  the lowest risk was associated with Bracco Diagnostic’s Prohance and Multihance.  However, the agency said “the data do not appear to rule out an NSF risk for each of the agents.” FDA reviewers said the extent of risk from any of the agents was unknown. One study of Omniscan estimated the chances of developing NSF was 4 percent among patients with severe kidney impairment.

According to a Reuters report, Covidien has already decided to modify the labeling of OptiMARK.  A spokesperson for the company  told Reuters that “it was prudent to act now, rather than wait for a causal link… to be established” between the imaging drugs and NSF.

Though the agency’s drug safety unit said the risk associated with the gadolinium contrast dyes “does not compel removal of specific (imaging agents) from the U.S. market”,  it has recommended that the drug labels note the varying levels of risks with each product. An  outside panel of experts will take up the issue in December.

NSF is a debilitating disease that leads to excessive formation of connective tissue in the skin and internal organs. It is characterized by high blood pressure, burning, itching, swelling and hardening of the skin. Other symptoms include red or dark patches on the skin; pain deep in the hip bones or ribs and muscle weakness. NSF can progress to the point of causing severe stiffness in joints, and it can lead to death. NSF is a relatively new disease. In fact, the first known diagnosis of NSF only occurred in 1997, but it wasn’t until September 2000 that details of the disease were published in the medical journal Lancet.

It appears that NSF only develops in people with pre-existing kidney disease. In 2006, Dutch researchers were the first to link NSF with the use of gadolinium contrast dyes. In September 2007, the FDA asked the manufacturers of all gadolinium contrast dyes to add a black box warning to the product labels about its association with NSF. The FDA also warned that patients with kidney disease should avoid gadolinium contrast agents, and that the lowest possible dosage should be administered to such patients if use of the dyes cannot be avoided.

Gadolinium contrast dyes are approved for use in MRI procedures, and are sometimes used off-label in MRA studies.