FDA Adds Boxed Warning to Clopidogrel

The FDA has added a boxed warning to the label for clopidogrel, the anti-blood clotting medication marketed as Plavix, because some patients do not effectively metabolize the drug and may not receive its full benefit.

The agency added information about poor metabolizers to clopidogrel's drug label last year. However, a boxed warning has been added -- based on additional data reviewed by the FDA -- to highlight the reduced effectiveness of the drug in certain patients and to recommend that physicians consider use of other anti-platelet medications or alternative dosing strategies for clopidogrel in patients identified as poor metabolizers.

For clopidogrel to work, enzymes in the liver -- particularly CYP2C19 -- must convert the drug to its active form. The FDA said physicians should be aware that tests are available to determine a patient's CYP2C19 status.

The FDA also said patients should not stop taking clopidogrel unless advised to do so by their physician. However, the agency advised patients to talk to their physicians if they have concerns about clopidogrel or to find out if they should be tested.

Manufacturers Sanofi-aventis U.S. and Bristol-Myers Squibb Co. said in a news release (7-page PDF; About PDFs) that 3 percent of the U.S. population are poor metabolizers. The rate varies by race, affecting 2 percent of whites, 4 percent of blacks and 14 percent of Chinese.

The FDA said physicians should be aware that although a higher dose regimen (e.g., 600 milligram loading dose followed by 150 milligram once daily) in poor metabolizers increases antiplatelet response, an appropriate dose regimen for poor metabolizers has not been established.