Pharmacogenetics and anticoagulant therapy

Warfarin and other coumarins are metabolized by the cytochrome P450 2C9 complex. Common single-nucleotide polymorphisms ( SNPs) in this enzyme are associated with an exaggerated elevation in the INR during warfarin initiation and an increased risk of bleeding. These observations suggest that patients known to carry the putative SNPs should be started on lower doses of warfarin therapy or have their INR values monitored more frequently during warfarin initiation. Such clinical variables as age, body surface area, and concomitant medications also play important roles in determining the maintenance dose of warfarin. Thus, a comprehensive dosing algorithm offers the most promising approach to estimating the therapeutic dose of warfarin a priori and to preventing hemorrhage during warfarin induction.