The influence of fibrate initiation on INR and warfarin dose in patients receiving chronic warfarin therapy

Several drug interaction compendia report a risk of warfarin potentiation after initiation of a fibrate; however, the evidence of this interaction is limited. The objective of this study was to evaluate warfarin dose and international normalized ratio (INR) response among a large sample of patients receiving chronic warfarin who initiated a fibrate. This was a retrospective, one-sample, pre-to-post study. Adult patients who were receiving chronic warfarin therapy at the time of gemfibrozil or fenofibrate dispensing between 1/1/2000 and 3/31/2016 were included. Patients had at least one and two therapeutic INRs during the 90 days prior to (baseline) and after (follow-up), respectively, fibrate initiation. Comparison of stable warfarin dose:INR ratio between the baseline and follow-up periods and assessment of safety outcomes during follow-up were performed. There were 321 patients included. Patients were predominantly male (62.6%) with an indication of atrial fibrillation (44.2%). The mean warfarin dose:INR ratio was equivalent between the baseline and follow-up periods (13.4 mg/INR [+/- 6.9] vs. 13.5 mg/INR [+/- 7.5], respectively, p = 0.711). Rates of thromboembolism, bleeding, and all-cause mortality in the 90-day follow up were 0, 0.6, and 1.2%, respectively. Although individual patients may have labile INRs after fibrate initiation, no significant interaction between fibrate and warfarin in a large sample of real world patients was identified. The utility of additional INR monitoring after fibrate initiation in otherwise stable patients receiving chronic warfarin therapy is unclear.