Impact of Drug Interactions on Major Bleed Rates in Patients Taking Direct Oral Anticoagulants.

Background: While direct oral anticoagulants (DOACs) have less stringent monitoring, favorable pharmacokinetics, and fewer drug interactions compared to warfarin, there is still a potential for drug-drug interactions. There is limited evidence showing total impact of DOAC drug interactions on major bleeding events. Methods: This was an IRB-approved retrospective, case control, single center study. Patients were included if they had received a DOAC from January 2012 to September 2019 and were identified for major bleeding events and matched to a control group. The primary objective was to compare the presence of major drug interactions between patients on DOACs who did and did not have a major bleeding event. The secondary objectives were to compare the impact of specific interacting drug classes and their additive effects on major bleeding events. Results: There were 122 patients included in the study. While the number of patients on at least one interacting medication within duration of DOAC use was numerically higher in the bleed group (85% vs 72%), this was not significant (P = .077). There were significantly more patients on at least three interacting medications within the last 3 months of the study period in the bleed group (n = 9 vs 1), with significantly higher use of aspirin (n = 38 vs 17) and rate control agents (n = 24 vs 11). Conclusion: There may be a cumulative effect on risk of bleeding if patients are on three or more interacting medications concomitantly with a DOAC. This risk of bleeding may be higher with aspirin and rate control agents.

Impact of prophylactic oseltamivir on INR in patients on stable warfarin therapy.

Influenza prophylaxis with oseltamivir is recommended for exposed high-risk patients. Patients with many comorbidities have an increased likelihood of co-administration of oseltamivir and warfarin. Evidence of a drug interaction is conflicting in the literature and is limited to a 5-day treatment course. This study evaluates the impact of prophylactic oseltamivir on international normalized ratio (INR) in patients taking warfarin. This retrospective cohort study conducted within the Veterans Health Administration included patients on warfarin who received oseltamivir for influenza prophylaxis. The primary endpoint was change in INR from baseline to day 10 of oseltamivir treatment. Secondary endpoints included change in INR based on renal function and duration of oseltamivir prophylaxis, trend in INR, and frequency of bleeding and thrombosis events. A total of 1041 patients were included and received oseltamivir for a mean of 12.9 days. The mean post-oseltamivir INR was significantly increased compared to the pre-oseltamivir INR (2.39 to 2.52; p < 0.001). Patients with a creatinine clearance of 31-60 mL/min had a significant increase in INR (2.40 to 2.59; p < 0.01). There was an increase in INR when oseltamivir was used for 7 or 8-10 days. Of included patients, 5.1% and 1.8% had a recorded thrombosis or bleeding event, respectively. There was a significant increase in INR in patients on chronic warfarin therapy and concomitant prophylactic oseltamivir, but this change may only be clinically significant for certain patient populations. The most impact on INR was within 7-10 days of oseltamivir initiation and in patients with impaired renal function.