March 11, 2010 - The FDA has put a new "black box" warning on the anti-clotting drug Plavix, the second best-selling drug in the world.
The new label warns that normal doses of Plavix have a potentially deadly lack of effect in 2% to 14% of patients.
Such patients are so-called "poor metabolizers" who carry a variant CYP2C19 gene affecting the enzyme that converts Plavix into its active form.
A less strident warning about poor metabolizers first appeared on the Plavix labels in May 2009. Based on new information from a drugmaker-funded study and other research, the FDA has now strengthened the warning.
A genetic test can tell whether a person is a poor metabolizer. The test costs about $500, according to Courtney Harper, PhD, director of the FDA's division of chemistry and toxicology devices. But cost isn't the only issue.
"The time to get a test result varies. It may be a few hours to a day or two, or other labs may take a few weeks," Harper said at a news conference held to discuss the FDA action.
"Unfortunately, waiting to see if Plavix will work isn't easy. This drug is to keep you from having a heart attack or stroke or dying, so waiting is not a good idea," he said at the news conference. "And this drug is used acutely, when a person is having angioplasty. So you really can't wait for the test results in that case. But for people who had a heart attack some time ago, they might want to wait for the test."
Different races are more or less likely to carry the CYP2C19 gene that makes them poor metabolizers.
"The frequency is about 2% of Caucasians, 4% of blacks, and 14% of Chinese," Mary Ross Southworth, PharmD, deputy director for safety in the FDA's division of cardiovascular and renal products, said at the news conference.
People carry two copies of each gene. Those who inherit two copies of the CYP2C19 gene are poor metabolizers of Plavix, and those with one copy are intermediate responders. There is also a variation of the gene that makes a person a "hyper-responder" to Plavix.
The FDA wants doctors to discuss Plavix options with patients. Right now, those options include using Effient, another anti-clotting drug that is not affected by the CYP2C19 gene. Another option is to use a double dose of Plavix.
"The data are not clear. There is more uncertainty than we wish we had about exactly what to do for these patients," Temple said.
Plavix, from Bristol-Myers Squibb and Sanofi Aventis, is used to prevent heart attacks and strokes. It's particularly useful in preventing deadly blood clots in patients who have received stents to reopen blocked arteries.