A clinically significant interaction between warfarin and simvastatin is unique to carriers of the CYP2C9*3 allele

Background: Simvastatin interacts with warfarin, but the strength of the interaction varies between individual patients, indicating a genetic predisposition. Patients & methods: The influence of the CYP2C9*2 and CYP2C9*3 polymorphisms on the interaction between simvastatin and warfarin was analyzed in data from 1132 patients. Results: Simvastatin use reduced warfarin dose requirements by 29% in carriers of the CYP2C9*3 allele, compared with 5% in noncarriers. A regression model showed a significant influence of CYP2C9*3 on the drug drug interaction, predicting a warfarin dose reduction of 25% in CYP2C9*3 heterozygotes and 43% in CYP2C9*3 homozygotes. Conclusion: Our data indicate that the CYP2C9*3 polymorphism predisposes for a pharmacologic interaction between warfarin and simvastatin.