Annotation of Health Canada Santé Canada (HCSC) label information
for clopidogrel
and CYP2C19
Summary
The product monograph for clopidogrel (PLAVIX) states that CYP2C19 poor metabolizers may be at increased risk for experiencing cardiovascular events when taking the drug at recommended doses as compared to normal CYP2C19 metabolizers, and that an alternative treatment or treatment strategies should be considered in these patients.
Annotation
Clopidogrel (PLAVIX) is indicated for the secondary prevention of atherothrombotic events in patients with atherosclerosis. Excerpts from the clopidogrel (PLAVIX) product monograph:
PLAVIX is a pro-drug, which requires metabolism by the hepatic cytochrome CYP2C19 to form the active thiol metabolite.
In patients who are CYP2C19 poor metabolisers, PLAVIX at recommended doses forms less of the active metabolite of clopidogrel and has a smaller effect on platelet function. Poor metabolisers with acute coronary syndrome or undergoing percutaneous coronary intervention treated with PLAVIX at recommended doses may exhibit higher cardiovascular event rates than do patients with normal CYP2C19 function. Consider alternative treatment or treatment strategies in patients identified as CYP2C19 poor metabolisers.
The CYP2C19*1 allele corresponds to fully functional metabolism while the CYP2C19*2 and CYP2C19*3 alleles are nonfunctional. The CYP2C19*2 and CYP2C19*3 alleles account for the majority of reduced function alleles in white (85%) and Asian (99%) poor metabolisers. Other alleles associated with absent or reduced metabolism are less frequent and include, but are not limited to, CYP2C19*4, *5, *6, *7 and *8. A patient with poor metaboliser status will possess two loss-of-function alleles as defined above.
For the complete product monograph text with sections containing pharmacogenetic information highlighted, see the clopidogrel product monograph.
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