FRIDAY, March 12, 2010 (HealthDay News) -- The anti-clotting drug Plavix must now carry a "black box" warning on its label, alerting patients and doctors that some people don't metabolize the medication properly, U.S. health officials said Friday.
Patients with a certain genetic variation can't convert the blood thinner into its active form, which puts them at risk for heart attack and stroke, the U.S. Food and Drug Administration warned.
"If the patient makes less of the active form, there is less antiplatelet effect in the blood, and the patient may not receive the full benefit of Plavix treatment," Mary Ross Southworth, FDA's deputy director for safety in the division of cardiovascular and renal products at the Center for Drug Evaluation and Research, said during an afternoon press conference.
These patients are called poor metabolizers, she said.
Clopidogrel (Plavix) is generally prescribed after a heart attack, stroke or a procedure to open blocked coronary arteries. It usually makes platelets less likely to form blood clots, thus reducing the risk of heart attack, unstable angina, stroke and cardiovascular death in patients with cardiovascular disease.
For the drug to do its work, liver enzymes, especially one called CYP2C19, must convert the drug to its active form. In patients with low levels of the enzyme, the drug may be less effective in preventing heart attack, stroke and cardiovascular death, according to the FDA.
About 2 percent to 14 percent of people fall into this category, with the percentages varying by race. About 2 percent of whites have the variation, while 4 percent of blacks and 14 percent of Chinese people do, Southworth said.
But patients should not stop taking Plavix without consulting their doctor, the FDA said, noting a test to assess the CYP2C19 genotype can determine if a patient is a poor metabolizer.
In May 2009, the FDA required mention of the problem on the bottle label, but additional data from a recent study has caused the agency to call for the "black box" alert, its strongest warning.
That study, which the FDA asked Plavix's makers to conduct, found less antiplatelet activity in people who were poor metabolizers than in patients who had no problem converting the drug.
However, when Plavix was given at higher-than-usual doses, the poor metabolizers showed more active drug in their blood than when they received lower doses, the researchers noted.
Patients who cannot convert Plavix well should use another anti-clotting drug or try an alternate strategy, such as a dosage increase, the FDA advised. Anti-clotting drugs that might be substituted for Plavix include ticlopidine (Ticlid) and prasugrel (Efient), the FDA said.
>"Efient doesn't need this enzyme as much to form its active metabolite so it does not have the primary problem, and we know some people will consider using that," Dr. Robert Temple, director of the FDA's Office of Drug Evaluation, said during the press conference.
On the other hand, "ticlopidine was the first member of this class and has a fairly high frequency of some unpleasant hematologic problems, so it has lost popularity considerably," he said.
Another recent study found that heart attack patients taking Plavix plus a proton pump inhibitor, such as Prilosec or Nexium, may be at increased risk of death or another heart attack, because this combination also prevents Plavix from being fully metabolized. The FDA is conducting a safety review about potential interactions of these commonly prescribed medications.
Plavix is made in partnership by two pharmaceutical giants, Bristol-Myers Squibb and Sanofi Pharmaceuticals. A Bristol-Myers spokesperson told the Associated Press that the new labeling would be added to Plavix during the next two months.
For more information on the new warning, visit the U.S. Food and Drug Administration.