New Plavix Warning: Lack of Effect in Many People

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.
For many patients at risk of a second heart attack or stroke, time is of the
essence, noted Robert Temple, MD, director of the FDA's office of medical
policy.
"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.
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