Effect of Oseltamivir on Bleeding Risk Associated with Warfarin Therapy

Abstract

Warfarin is a commonly used oral anticoagulant and its interaction with other drugs can result in serious thrombotic or bleeding events. Currently, there is no definitive evidence on the possibility of an interaction between warfarin and oseltamivir. The objective of this study was to investigate whether a possible drug interaction between oseltamivir and warfarin exists. A retrospective review of patients on anticoagulation therapy who took oseltamivir from 1 September 2009 to 28 February 2010 at Seoul National University Hospital, Seoul, Korea, was carried out. Among 15 patients who were tested for prothrombin time/international normalized ratio (PT/INR) [hereafter referred to as INR] within 10 days of starting oseltamivir therapy and had previously stable INR values, seven patients had an increase in INR levels after oseltamivir administration, and the other eight patients maintained stable INR levels. The mean ± SD INR value was 2.08 ± 0.46 prior to the administration of oseltamivir and 5.15 ± 2.00 after treatment with oseltamivir (measured a mean ± SD 5.7 ± 2.5 days after the first dose of oseltamivir) in the INR-increased group and, respectively, 2.03 ± 0.40 and 1.97 ± 0.54 (measured 6.4 ± 2.5 days after the first dose of oseltamivir) in the INR-unaffected group. The dosage and duration of oseltamivir treatment were similar whether the INR values increased or not. There were bleeding events such as blood-tinged sputum and bloody ascites in three patients in the INR-increased group. The INR level recovered within 5 days after discontinuation of warfarin in these three patients. The positivity rates for influenza A H1N1 were not different between the INR-increased group and the INR-unaffected group. This case series suggests the possibility of a potential interaction between warfarin and oseltamivir. Further well designed prospective studies and genetic evaluations are needed to determine the exact nature of the interaction between warfarin and oseltamivir.