Annotation

Clopidogrel (Plavix) is a P2Y12 platelet inhibitor indicated for acute coronary syndrome, recent myocardial infarction, recent stroke or peripheral arterial disease.

Excerpt from the clopidogrel (Plavix) drug label:

The effectiveness of Plavix results from its antiplatelet activity, which is dependent on its conversion to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19...Plavix at recommended doses forms less of the active metabolite and so has a reduced effect on platelet activity in patients who are homozygous for nonfunctional alleles of the CYP2C19 gene, (termed "CYP2C19 poor metabolizers"). Tests are available to identify patients who are CYP2C19 poor metabolizers...Consider use of another platelet P2Y12 inhibitor in patients identified as CYP2C19 poor metabolizers...

Twenty-one studies involving 4,520 subjects have shown that CYP2C19*2, CYP2C19*3, and other CYP2C19 loss-of-function alleles are associated with diminished antiplatelet responses to treatment with clopidogrel. CYP2C19 participates in the formation of both the active metabolite of clopidogrel and the 2-oxo-clopidogrel intermediate metabolite. Individuals with CYP2C19 loss-of-function alleles have reduced exposure to the active metabolite of clopidogrel, leading to less platelet inhibition or higher residual platelet reactivity. Key publications on pharmacogenetic studies of response to clopidogrel include: [Articles:19106083, 19106084, 19108880, 19193675].

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the clopidogrel drug label.

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