Frequency of Concurrent Use of Warfarin with Potentially Interacting Drugs


University of Washington Medical Center, 1959 Northeast Pacific Street, Room BB112, Box 356015, Seattle, WA 98195; e-mail:


Study Objective. To determine the rates of concomitant use of drugs known to interact with warfarin by increasing the prothrombin time expressed as the international normalized ratio (INR), decreasing the INR, or increasing bleeding risk without apparent changes in INR in a cohort of patients receiving long-term warfarin therapy.

Design. Retrospective, longitudinal cohort study.

Setting. Large pharmacy benefits manager database.

Patients. A total of 134,833 patients who were prescribed long-term warfarin from June 1, 1999–May 31, 2000.

Measurements and Main Results. Longitudinal pharmacy claims from the pharmacy benefits manager database were reviewed to identify coprescription of warfarin and drugs associated with significant interactions with warfarin. Of the 134,833 patients receiving long-term warfarin therapy, 109,998 (81.6%) were prescribed a concurrent prescription for at least one potentially interacting drug, including 87,346 (64.8%) who were prescribed one or more concomitant drugs associated with interactions known to increase the INR. Acetaminophen-containing products, prescribed for 22.7% of patients receiving concomitant prescriptions, and thyroid hormones, prescribed for 17.5%, were the most commonly prescribed concurrent drugs associated with an increased INR response. The most frequently prescribed interacting agents associated with a decreased INR response were trazodone (2.2%) and carbamazepine (1.1%). The most commonly prescribed agents independently associated with increased bleeding risk were cyclooxygenase-2 inhibitors.

Conclusion. Many patients receiving warfarin therapy are treated with concomitant drugs that may interact with the warfarin. The high percentage of patients taking drugs that may increase INR or bleeding risk is a reminder that bleeding events are a likely adverse outcome of combining drugs that interact with warfarin. Careful warfarin management is necessary to avoid adverse events associated with drug interactions.