FDA Updates Prescription Guidelines for Blood Thinner

THURSDAY Aug. 16, 2007 -- The U.S. Food and Drug Administration announced Thursday a labeling update for the widely prescribed blood thinner warfarin (Coumadin), advising doctors that patients' genetic makeup can affect how they respond to the drug.

Responses to warfarin depend on a patient's variants of the genes CYP2C9 and VKORC1. About 30 percent of patients -- many of them heart patients -- who take warfarin have these gene variants.

These variations can determine how fast warfarin is metabolized, Larry Lesko, director of the FDA's office of clinical pharmacology at the Center for Drug Evaluation and Research, said during a teleconference. "Patients with these variations may need lower doses of warfarin than patients with the usual forms of these genes.

"The label change explains that certain people are likely to respond very differently to the drug if they happen to carry variations of two of their genes," Lesko said. The label updates are based on recent studies that found patients' response to the drug depends on these gene variations, he added.

In the United States, some 2 million people start taking warfarin every year to prevent blood clots, heart attacks and stroke, according to the FDA. Warfarin is tricky to use, because the correct dose varies and depends on risk factors, including diet, age, and other medications the patient is taking.

If the warfarin dose is too high, there is the risk of life-threatening bleeding. If the dose is too low, there is a risk of developing blood clots. Dosing is particularly important when starting the drug, the FDA said.

The FDA isn't mandating that doctors obtain genetic tests before prescribing warfarin but suggests that it is something doctors may want to consider when prescribing the drug.

"Doctors and other health-care professionals may well decide to incorporate genetic information along with more traditional risk factors in estimating their patient's warfarin doses," Lesko said. "It may improve the safe use of warfarin."

Lesko noted that genetic tests for the gene variants can cost $125 to $500. The tests may not be readily available in some parts of the United States, he said.

Dr. Janet Woodcock, the FDA's deputy commissioner and chief medical officer, noted during the teleconference that there isn't enough data to make genetic testing a mandate when prescribing warfarin.

"We have to test how good it will be to use genetic information versus the current methods, which are not perfectly satisfactory, but work to initiate warfarin therapy. Then we will have an answer to that question," Woodcock said.

Warfarin is the second most common drug to blame for emergency room visits for adverse drug events, after insulin, the FDA said.

Currently, patients need to have several blood tests over several weeks to determine their optimal warfarin dose.

Patients taking warfarin need to have their blood checked monthly to see if the drug is working properly. The test is called the PT -- or prothrombin time -- test, which evaluates the blood's ability to clot. The results are measured in seconds and compared with the expected value in healthy people.

The changes to the label will be made by manufacturers of warfarin, the generic version of Coumadin. Bristol-Myers Squibb Co., of Princeton, N.J., is the manufacturer of Coumadin, the FDA said.

More information

For more on warfarin, visit the U.S. National Library of Medicine.

Posted: August 2007


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