Need for pharmacogenomic information also for generic medications: recommendation of the European Society of Pharmacogenomics and Theranostics (ESPT).

Abstract

As of 2007, PLAVIX (the original brand name of clopidogrel) had been the second top-selling drug in the world and is, presently, prescribed and marketed in nearly 110 countries. Clopidogrel is currently the thienopyridine of choice for dual antiplatelet therapy (in combination with aspirin) in patients with the full spectrum of acute coronary syndrome and in those undergoing percutaneous coronary intervention and stenting. In a plethora of pharmacogenomic studies on PLAVIX, it has been shown that clopidogrel is a prodrug that requires biotransformation to an active metabolite by CYP450 enzymes (mainly CYP2C19) and paraoxonase 1 (PON-1). There is signifi cant inter-individual variability in the response to PLAVIX, with up to 40 % of patients being classifi ed as non-responders, poor responders, or resistant to this drug. Pharmacogenomic information on PLAVIX reveals that genetic polymorphisms of CYP enzymes (most commonly CYP2C19*2), PON-1, and also the ABCB 1 transporter contribute to variation in the response of individual patients to the drug. In March 2010, the Food and Drug Administration (FDA) released a “ boxed warning ” on PLAVIX addressing the need for pharmacogenomic testing (for detecting CYP2C19 loss-of-function polymorphisms) to identify patients ’ altered PLAVIX metabolism, and thus their risk for a suboptimal clinical response to this drug. On the basis of an expanding database, and as an approach to the FDA boxed warning, the American College of Cardiology Foundation/ American Heart Association-convened writing committee developed an evidence-based guideline, “ Recommendations for Practice, ” in July 2010. These documents were validated in France in October 2010 and the SmPC (Summary of Product Characteristics) of PLAVIX was updated accordingly by the French regulatory agency (AFSSAPS).