title: Interaction of rofecoxib and celecoxib with warfarin.
abstract: 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.
authors.affiliation: VA San Diego Healthcare System, Pharmacy (119), 3350 La Jolla Village Drive, San Diego, CA 92161, USA. monica.schaefer@med.va.gov
authors.forename: Monica G
authors.initials: MG
authors.lastname: Schaefer
authors.forename: Brian K
authors.initials: BK
authors.lastname: Plowman
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Morreale
authors.forename: Melissa
authors.initials: M
authors.lastname: Egan
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D000925:Anticoagulants / Q000009:adverse effects*; D000068579:Celecoxib; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007783:Lactones / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins; D011446:Prospective Studies; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides / Q000009:adverse effects* / Q000494:pharmacology; D013450:Sulfones; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D014859:Warfarin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib