Warning about Plavix and Low Metabolisers
Prescribing information for clopidogrel (Plavix) will now include a boxed warning that the drug can be less effective in poor metabolizers, the FDA indicated.
The new warning suggests that many if not all patients on clopidogrel should undergo genetic testing to determine whether they have variants of the CYP2C19 gene associated with poor metabolism of the antiplatelet drug.
Clopidogrel is actually a prodrug that requires metabolic activation by the CYP2C19 enzyme to become effective. Poor metabolizers get little or no benefit from the drug at standard doses, and therefore are at increased risk for thrombotic events and death, the FDA said.
The drug’s label has carried a similar warning since May 2009, but the FDA said today that “it was important to highlight this risk in a boxed warning” in light of a subsequent review of data.
Seven different variants of the CYP2C19 gene are associated with poor metabolism of clopidogrel. According to the FDA, patients with two loss-of-function alleles, which do not have to be identical, will be poor metabolizers.
The agency estimated that 2% to 14% of patients are poor metabolizers, with some racial-ethnic groups more likely to be affected than others. Whites have the lowest prevalence of poor metabolism and Asians have the highest.