WARFARIN DOSAGE ADJUSTMENT IN PATIENTS WITH GENETIC VARIABILITY

Warfarin is a potent drug that when used judiciously and monitored closely, leads to substantial reductions in morbidity and mortality from thromboembolic events. However, even with careful monitoring, initiation of warfarin dosing is associated with highly variable responses between individuals and challenges achieving and maintaining levels within the narrow therapeutic range that can lead to adverse drug events. Genetic factors most correlated with warfarin dose requirements are variations in the genes encoding the enzymes cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKOR). Patients receiving warfarin who possess one or more genetic variations in CYP2C9 and VKORC1 are at increased risk of adverse drug events and require significant dose reductions to achieve a therapeutic international normalized ratio (INR). The results of this study suggests that the CYP2C9*2 and CYP2C9*3 polymorphisms associates an increased risk for over anticoagulation and bleeding events among patients using warfarin anticoagulant, although small numbers in some cases would suggest the need for caution in interpretation. To reduce the risk of adverse reactions in patients, screening for CYP2C9 variants helps the clinicians to develop the new required dosing protocols and surveillance techniques in patients using warfarin(14). The theme of this review was explaining, of association of CYP2C9*2 & CYP2C9*3 variants are in over anticoagulation & bleeding events in warfarin therapy.