The label for  OptiMARK gadolinium contrast agent will now warn that it should not be administered to people with severe kidney impairment.  The decision by Covidien to make the label change comes on the heels of a the U.S. Food and Drug Administration review that found that OptiMARK was one of three gadolinium agents with the highest risk of nephrogenic systemic fibrosis (NSF).

In a statement released by Covidien yesterday, the company said it is  implementing its OptiMARK label change in all countries where OptiMARK contrast agent has been approved for sale, in accordance with local regulatory requirements. Covidien also will update its educational materials to help physicians make informed decisions regarding the appropriate use of OptiMARK. Mallinckrodt Inc., a Covidien company, has submitted this label change to the FDA and says it is implementing the new label in the U.S. effective immediately.

“For the small percentage of the U.S. population – less than 0.5 percent – with severe renal impairment, we believe it is prudent to act now, rather than wait for a causal link between GBCAs (gadolinium based contrast agents) and NSF to be established. Although the label already advises caution when using GBCAs with these patients, we are voluntarily taking this next step to help ensure this small, at-risk population does not receive administration of a contrast agent that could pose a risk of NSF.” said Dr. Herbert Neuman, Vice President, Medical Affairs and Chief Medical Officer, Pharmaceuticals, Covidien.

Gadolinium contrast dyes are approved for use in MRI procedures, and are sometimes used off-label in MRA studies. These agents were first introduced in the 1980s, and there are currently five such dyes on the market. In addition OptiMARK, other agents on the market include Prohance and Multihance, both by Bracco Diagnostics, Bayer Healthcare’s Magnevist and GE Healthcare’s Omniscan.

Yesterday, we reported that an FDA review had found that OptiMARK, Magnevist and Omniscan carried a higher risk of NSF than other gadolinium agents on the market.    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.

It appears that NSF only develops in people with pre-existing kidney disease. 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.