Preemptive dose reduction of warfarin in patients initiating metronidazole

The goal of this study was to determine if preemptive dose reduction (PDR) of warfarin is effective in maintaining therapeutic anticoagulation in patients initiating metronidazole.

This is a retrospective, single-center, cohort study in a pharmacist-managed anticoagulation clinic of a university affiliated Veteran's Affairs (VA) Medical Center. Subjects were anticoagulation patients initiating metronidazole between 1 January 2002 and 30 March 2009. At the time of metronidazole initiation, patients were managed with PDR of warfarin or no dose reduction. The primary outcome was the average change in International Normalized Ratio (INR) between patients that received PDR vs. those that did not.

In total, 20 patients met inclusion criteria with seven patients receiving PDR at the time of initiation of metronidazole, whereas 13 did not. Patients managed with PDR and those that were not were similar in age (mean±SD 69.4±12.9 years vs. 72.1±9.9 years, p=0.61), mean baseline INR before metronidazole (2.58±0.49 vs. 2.57±0.66, p=0.98), and mean time to follow-up after initiation of metronidazole (5.6±2.9 days vs. 7.0±3.7 days, p=0.40), respectively. The primary outcome was statistically significant with a mean difference in INR of 1.28 (p=0.01) between patients manag-ed with PDR vs. those that were not. The mean preemptive warfarin dose reduction was 34.6%±13.4% which resulted in no significant increase in INR (p=0.61). Secondary outcomes including INR values >4.0 (0% vs. 46%, p=0.05), the average number of warfarin doses omitted (0.43±0.79 vs. 1.15±1.27, p=0.17), use of phytonadione or fresh frozen plasma, and rates of bleeding events were not significantly different be-tween groups. No thromboembolic events occurred during the 30 days following metronidazole therapy.

In patients determined to be appropriate candidates for PDR, a 30%-35% reduction in mean daily warfarin dose was effective in maintaining therapeutic anticoagulation in patients started on concomitant metronidazole.