Clopidogrel, the chemical name for Plavix, is an anti-platelet medication used to reduce the risk of heart attacks and strokes in individuals with heart disease. See also the Wikipedia article on clopidogrel. Note that clopidogrel is a pro-drug metabolized by CYP2C19.
Because clopidogrel inhibits CYP2C9 at high doses, it may interfere with the metabolism of drugs processed by the liver enzyme CYP2C9, and individuals with CYP2C9 SNP variants that encode lower metabolizers to begin with would presumably be at greater risk for such side effects when taking clopidogrel at the same time as drugs metabolized by CYP2C9.
SNPs influencing the metabolism (or effectiveness) of clopidogrel include:
- rs4244285: patients who are prescribed clopidogrel and who carriers of this CYP2C19*2 SNP are at 3-4x increased risk for heart attacks or other adverse cardiovascular events [PMID 19108880][PMID 19106083][PMID 19106084] Such patients may require higher clopidogrel dosing or the use of alternative thienopyridines such as prasugrel or ticagrelor. [1]
This has now (2010) been acknowledged by the FDA, who have added a boxed warning to clopidogrel, alerting patients and health care professionals that the drug can be less effective in people who have CYP2C19 variants and cannot convert the drug as effectively to its active form. [2]
Some medical centers offer genetic screening tests for patients who have conditions that are often treated with simvastatin, clopidogrel, or warfarin. [3]
As of May 2011, the CPMC is revealing to its participants their CYP2C19 status, primarily in order to determine the suitability of taking clopidogrel. Coriell states that they determine CYP2C19 status based on the following SNPs: