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FDA notes role genetic testing can play in safer use of blood thinner

WASHINGTON – Federal health officials are stopping short of recommending genetic tests for patients on the blood-thinner warfarin, even though they have said such screenings could prevent thousands of complications each year.

Warfarin, sold under the brand name Coumadin and in generic forms, on Thursday became the first widely used drug to include genetic testing information on its label. The information can help doctors determine how best to prescribe the drug.

"This means personalized medicine is no longer an abstract concept but has moved into the mainstream," the Food and Drug Administration’s clinical pharmacology chief, Larry Lesko, said in announcing the label change.

The updated label for warfarin suggests that lower doses may be best for patients with variations in two specific genes. One produces an enzyme that helps the body metabolize warfarin and other medicines; the second produces the blood-clotting protein that warfarin blocks.

The FDA has not changed its dosing recommendations for the drug, and tailoring the proper dosage remains largely a matter of trial and error.

A patient’s age, weight, diet and other prescription drug use all play a role in determining a proper dose. Patients taking too much warfarin can bleed to death. If people take too little of the drug, it can fail to protect them from deadly blood clots and stroke.

Genetic testing can reveal which patients may require less of the drug and lead doctors to recommend an initial dose closer to the lower end of the scale, FDA officials said.

"This issue of getting people to the right dosage sooner is really important. The recent label change is a huge help in this regard," said Dr. Robert Epstein, chief medical officer of Medco Health Solutions Inc.

An analysis done by the prescription benefit management company found that 60 percent of 147,000 patients who began taking warfarin in 2005 had their dosage adjusted during the first 12 months on the drug, Epstein said.

Rebecca Burkholder, vice president of health policy for the National Consumers League, said the FDA’s action was a good first step. But she said that once patients are on the drug, they still must have regular blood tests to see if it is working properly.

Changes in diet, for example, can lead to further dosing tweaks – something even genetic testing will not eliminate.

A survey done by the group last year found too few patients on warfarin understood some basic steps they were supposed to take to avoid complications.

FDA economists estimate the genetic testing could prevent 85,000 "serious bleeding events" and 17,000 strokes a year, according to a November 2006 study posted to the Web site of the American Enterprise Institute. The savings to the health care system could be $1.1 billion a year, though some people question that. The genetic tests can cost $125 to $500. About 2 million people start taking the drug each year.

Warfarin sends more than 43,000 people to the emergency room each year, the FDA economists said. That total is more than for any other drug except insulin, which diabetics use.

About one in three warfarin patients metabolizes, or clears, the drug differently than anticipated. Variations on two genes explain some of those differences.

One gene, CYP2C9, produces an enzyme that helps the body metabolize a variety of medicines, including warfarin. People whose bodies process warfarin more slowly would need a smaller dose.

A second gene, VKORC1, produces the blood-clotting protein that warfarin blocks. A patient’s body that churns out less of that protein also would need less warfarin.

FDA officials said they would hold off on recommending or requiring the tests for those genetic variants until the completion of studies to show whether doing so would actually benefit patients. An outside expert said doing otherwise would have been premature.

"What we need to do is find out whether genetic testing improves outcomes," said Dr. Brian Gage of Washington University in St. Louis.

The FDA was to have begun that type of study in November but scrapped it for lack of money. The National Institutes of Health has since announced plans for such a trial.

Bristol-Myers Squibb Co. makes Coumadin. A message left with a spokesman was not immediately returned. A half-dozen other companies make generic versions of the drug.