Interaction of rofecoxib and celecoxib with warfarin

• Published in: American journal of health-system pharmacy Vol. 60; no. 13; pp. 1319 - 1323
• Main Authors: Schaefer, MG, Plowman, BK, Morreale, AP, Egan, M
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Bethesda, MD ASHP 01.07.2003; American Society of Health Pharmacists
• Subjects: Aged; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anticoagulants - adverse effects; Biological and medical sciences; Celecoxib; Cross-Over Studies; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - adverse effects; Cyclooxygenase Inhibitors - pharmacology; Drug Synergism; Female; Humans; International Normalized Ratio; Isoenzymes - antagonists & inhibitors; Lactones - adverse effects; Lactones - pharmacology; Male; Medical sciences; Membrane Proteins; Prospective Studies; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Sulfonamides - adverse effects; Sulfonamides - pharmacology; Sulfones; Warfarin - adverse effects; International Normalized Ratio; Anticoagulants; Warfarin; Antiinflammatory agents; Drug Interactions; Rofecoxib; Toxicity; Celecoxib
• ISSN: 1079-2082; 1535-2900
• DOI: 10.1093/ajhp/60.13.1319

The interaction of celecoxib and rofecoxib with warfarin was studied. Patients stable on warfarin therapy and concurrently taking a cyclooxygenase-2 (COX-2) inhibitor comparator (traditional nonsteroidal antiinflammatory medications, salsalate, or acetaminophen) randomly received celecoxib 200 mg/day or rofecoxib 25 mg/day for three weeks. After a one-week washout period, the patients were crossed over to treatment with the opposite COX-2 inhibitor for three more weeks. The International Normalized Ratio (INR) was measured at baseline and at weeks 1, 2, and 3 of therapy with each COX-2 inhibitor by testing blood samples obtained by finger stick. Data for 16 patients were analyzed. The INR increased by 13%, 6%, and 5% on average in patients taking celecoxib at weeks 1, 2, and 3, respectively, and by 5%, 9%, and 5% in patients taking rofecoxib. Changes in the INR were statistically significant at week 1 for celecoxib and at week 2 for rofecoxib. Of the 12 subjects who had a clinically significant > or = 15% change in the INR while receiving either COX-2 inhibitor, 4 showed this change for both agents. Adverse drug reactions were similar for each COX-2 inhibitor, but the rate of edema requiring medical intervention was higher in the rofecoxib group. Significant increases in the INR were observed in patients who were stable on warfarin therapy after the addition of therapy with rofecoxib or celecoxib.