FDA clarifies label of warfarin

The Food and Drug Administration yesterday approved a labeling change for the widely used blood-thinning drug warfarin that will add information explaining that a person’s genetic makeup may call for a lower dosage.

Researchers at the FDA said studies reveal that a person’s response to warfarin, a generic drug, depends on two genetic variants. The agency is attempting to improve the safety of warfarin by describing the influence of genes to doctors. A lower dose may reduce the risk of dangerous bleeding in patients with the gene variations, the agency said.

“Today’s announcement means personalized medicine is no longer an abstract concept. It has moved into the mainstream where it is recommended as a factor in a drug used by millions of people every day ” said Larry Lesko, director of the clinical pharmacology office at the FDA.

The label change marks the first time the FDA will use gene-specific information on the label for a major drug. The agency already includes information about genetic testing on the labels of less-frequently used drugs for colon cancer and leukemia, among others. One drug, Genentech Inc.’s Herceptin for breast cancer, is designed especially for women whose tumor cells have a genetic abnormality.

Originally marketed as a rat poison, warfarin was prescribed more than 30 million times last year in the U.S., according to IMS Health, a pharmaceutical market-research firm. Warfarin is the generic version of Coumadin, manufactured by Bristol-Myers Squibb.

It trails only insulin in sending patients to the emergency room with negative drug reactions, the FDA said.

Proper dosing for warfarin is extremely important. Overdosing can cause excessive bleeding, but if the dose is too low, blood clots can occur. Therefore, the dosage levels must be individualized for each patient according to tests that evaluate the blood’s ability to clot properly.

The new labels will not recommend dosing levels for people with the gene variants, only advising genetic testing.

“Although genetic testing can currently identify who has these genetic variants, more studies are needed to explore the precise starting dose for these patients,” Dr. Lesko said. “FDA has been working with other government agencies and organizations to develop such studies under the auspices of our three-year-old Critical Path Initiative, which addresses the challenges of moving promising medical products from discovery to patient use.”

Doctors will not be required to test for the genes, the agency said, but emphasized that adding the labeling change gives health care providers a unique opportunity to use genetic tests to improve estimates of what is a reasonable dose of warfarin for each patient.

In November 2005, an outside FDA advisory committee voted 8-2 to put information about genetic tests on warfarin’s label, but the agency encountered resistance from doctors who say the benefits of genetic testing are unproven. The FDA hopes resistance is reduced with the new labels.

“Doctors and other health care professionals may well decide to incorporate genetic information, along with more traditional risk factors, in estimating their patients’ warfarin doses,” Dr. Lesko said. “It may improve the safe use of warfarin.”