Warfarin Institute of America
DEDICATED TO YOUR HEALTH SINCE 2000
CELECOXIB INTERACTIONS WITH WARFARIN (Coumadin, Jantoven)
The official package insert approved by the United States Food and Drug Administration states, Anticoagulant activity should be monitored, particularly in the first few days, after initiating or changing CELEBREX therapy in patients receiving warfarin or similar agents, since these patients are at an increased risk of bleeding complications. The effect of celecoxib on the anticoagulant effect of warfarin was studied in a group of healthy subjects receiving daily doses of 2-5 mg of warfarin. In these subjects, celecoxib did not alter the anticoagulant effect of warfarin as determined by prothrombin time. However, in post-marketing experience, serious bleeding events, some of which were fatal, have been reported, predominantly in the elderly, in association with increases in prothrombin time in patients receiving CELEBREX concurrently with warfarin. This was copied directly from the website www.Celebrex.com
Clinical Studies
Emery and colleagues compared celecoxib with diclofenac SR and found that they produced comparable pain relief. However, the celecoxib produced less gastrointestinal adverse events.
One other action which could be important is suppression of platelet function. Platelets are a part of the blood which has to do with clotting. If a drug suppresses platelet function it can lead to bleeding. Certainly this could be a problem if the drug is taken with warfarin (Coumadin, Jantoven). Leese and colleagues reported the results of a study in which they found that celecoxib did not suppress platelet function. Therefore, it did not increase the likelihood of bleeding.
Silverstein et al reported on the Celecoxib Long-term Arthritis Safety Study (CLASS Trial). This study compared doses of celecoxib at two to four times the recommended level with usual doses of ibuprofen or diclofenac. There were 4,573 patients evaluated after six months of treatment. Even at these high doses, there were fewer incidents of ulcer with celecoxib than with the other two drugs.
Goldstein et al examined the reports of fourteen trials to determine the incidence of gastrointestinal ulcer complications with celecoxib. They found that this complication was 8-fold lower with celecoxib than with naproxen, diclofenac or ibuprofen.
Schaefer reported on a study involving sixteen patients with stable warfarin (Coumadin, Jantoven) doses who were given celecoxib. Twelve of the patients had a 15% increase in the INR after one week. The authors judged this to be clinically significant.
Case Reports
Mersfelder reported the case of a 73-year-old woman who developed an INR of 5.7, five weeks after celecoxib was added to her medications which included warfarin (Coumadin, Jantoven).
Linder et al reported on the case of a 71-year-old man who was taking warfarin (Coumadin, Jantoven) for atrial fibrillation. He was started on celecoxib for arthritis. He was taking several other medications including cimetidine. One week after starting celecoxib, he was admitted to the hospital with black, tarry, loose stools and an INR of 4.0. The hospital course was uneventful and the patient was discharged on warfarin (Coumadin, Jantoven), but not celecoxib.
Stoner reported on the case of an “elderly”, psychiatric patient whose INR was elevated in conjunction with this combination. The warfarin (Coumadin, Jantoven) dose was 28 mg per week before the celecoxib was started. The INR only went up to 3.6 while the combination was being administered. After the celecoxib had been discontinued for one week, the INR was at 3.8. Sixteen days after the celecoxib was discontinued, the INR was 6.3. After the celecoxib was discontinued, warfarin (Coumadin, Jantoven) 21 mg per week kept the INR in the desired range.
Editor’s Note: It seems to me that this case report stretches the imagination to see how it could have been related to the interaction claimed. The INR only went to 3.6 while the combination was being administered. Those of us who monitor a lot of warfarin (Coumadin, Jantoven) patients know that INR changes of this magnitude happen frequently without any discernable cause. The fact that the INR kept increasing even more than two weeks after the supposed causative agent was stopped makes a strong case against this being a valid interaction. Then the warfarin (Coumadin, Jantoven) being restarted at a lower rate without celecoxib eliminates almost any possibility of this being an interaction.
Conclusions
So what does this mean for the person taking warfarin (Coumadin, Jantoven) who needs non-narcotic pain relief stronger than acetaminophen? My opinion is that celecoxib is a good choice. These studies and case reports indicate that this is true with celecoxib. The official celecoxib package insert recommends monitoring within a few days, also. The Mersfelder case fell well outside the few days follow-up recommended. The Linder case happened within a few days, but it also happened at an INR of 4.0 which is not usually considered particularly troublesome. Two gastroenterologists, Lehmann and Beglinger say that data from cost-effectiveness studies suggest, that Coxibs should currently be used only in patients with high risks of GI complications. It is not within the scope of this page to discuss the possible cardiac effects of celecoxib.
References:
Emery P et al. Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison. Lancet 1999;354:2106-2111.
Leese PT et al. Effects of celecoxib, a novel cyclooxygenase-2 inhibitor, on platelet function in healthy adults: a randomized controlled trial. J Clin Pharmacol 2000; 40:124-132.
Silverstein FE et al. Gastrointestinal toxicity with celecoxib vs nonstreoidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. JAMA 2000;284:1247-1255.
Goldstein JL et al. Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a novel COX-2 inhibitor.
Schaefer MG et al. Am J Health Syst Pharm. 2003;60:1319-1323.
Mersfelder TL et al. warfarin and celecoxib interaction. Ann Pharmacother 2000;34:325-327.
Linder JD et al. Cyclooxygenase-2 inhibitor Celecoxib: A Possible cause of gastropathy and hypoprothrombinemia. South Med J 2000;93: 930-932.
Stoner SC et al. Possible international normalized ratio elevation associated with celecoxib and warfarin in an elderly psychiatric patient. J Amer Geriatr Soc. 2003;51:728-729.
Lehmann FS et al. Impact of COX-2 inhibitors in common clinical practice a gastroenterologist's perspective. Curr Top Med Chem. 2005;5(5):449-64.
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Last updated May 6, 2006