Brian K Plowman, PharmD, MBA, BCPS, VA San Diego Health Care System; Monica G Schaefer, PharmD, VA San Diego Health Care System/University of the Pacific; Melissa Egan, PharmD, VA San Diego Health Care System; Anthony Morreale, PharmD, MBA, BCPS, VA San Diego Health Care System; Robert Terkeltaub, MD, VA San Diego Health Cre System

Objectives: To quantitate any clinically significant effect of rofecoxib or celecoxib therapy on warfarin dosing in a stable anticoagulated veteran population. The study will evaluate the potential need for prophylactic reduction in warfarin dosing in patients who are converted from their current arthritic or chronic pain medications including traditional NSAIDs, salsalate and acetaminophen, to celecoxib or rofecoxib.

Methods: The study consists of a crossover design and includes patients who are stable on warfarin therapy and a concomitant COX-2 comparator agent (traditional NSAIDs, salsalate, or acetaminophen) for rheumatoid arthritis, osteoarthritis or chronic pain. Subjects will be randomized to either receive celecoxib 200mg or rofecoxib 25mg daily in place of current COX-2 comparator medication. After three weeks on the initial randomized medication patients will undergo a one-week washout period in which they will be placed back on their pre-entry comparator agent. Patients will then be converted to the opposite COX-2 inhibitor for three weeks and serve as their own control. Weekly INR fingersticks will be performed to quantitatively assess changes in INR. A sample of 44 subjects is needed to detect a 15% difference in INR values and achieve 80% power with a level of significance of 0.05.

Results: Data collection is projected to begin mid-October with interim analysis of results planned for January.

Conclusions: Conclusions are pending data analysis.

Impact: The information gathered and analyzed from this study will serve as a guide to safely managing therapy in patients who require both warfarin anticoagulation and COX-2 therapy. Results will add to the existing data on COX-2 drug interactions and help to determine appropriate place in therapy of celecoxib and rofecoxib in our veteran population.