Bleeding complications in patients on celecoxib and warfarin
Non-selective non-steroidal anti-inflammatory drugs (nNSAIDs) used in combination with warfarin are associated with an approximately 3-fold increased risk of upper gastrointestinal bleeding (UGIB) compared with warfarin alone. Celecoxib, a selective inhibitor of cyclo-oxygenase 2 (COX-2), is associa...
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Published in | Journal of clinical pharmacy and therapeutics Vol. 30; no. 5; pp. 471 - 477 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Science Ltd
01.10.2005
Blackwell |
Subjects | |
Online Access | Get full text |
ISSN | 0269-4727 1365-2710 |
DOI | 10.1111/j.1365-2710.2005.00676.x |
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Abstract | Non-selective non-steroidal anti-inflammatory drugs (nNSAIDs) used in combination with warfarin are associated with an approximately 3-fold increased risk of upper gastrointestinal bleeding (UGIB) compared with warfarin alone. Celecoxib, a selective inhibitor of cyclo-oxygenase 2 (COX-2), is associated with less gastric mucosal injury and platelet dysregulation than nNSAIDs. We compared rates of bleeding complications in patients taking celecoxib and warfarin with those taking warfarin alone.
We performed a retrospective analysis using data from our Protime Clinic and pharmacy databases from January 2001 to April 2004. We identified 123 patients who took celecoxib and warfarin concurrently (overlap group). We compared rates of bleeding complications in this group with 1022 control patients who were taking warfarin alone. Bleeding complications were defined as major if they resulted in hospitalization, blood transfusion or death.
During approximately 1063 months of exposure to both celecoxib and warfarin, 10 bleeding complications were identified, only one of which was considered major. No patients had UGIB. In the control group, 116 bleeding complications were identified over approximately 16 520 months of exposure to warfarin alone, with 101 minor and 15 major events, including six episodes of UGIB. The relative risk of all bleeding complications was 1.34 (95% CI: 0.70-2.57) in the overlap vs. control groups, and for major bleeds was 1.04 (95% CI: 0.14-7.85).
There is a mild but non-significant increase in bleeding complications in patients taking celecoxib and warfarin compared with those taking warfarin alone. |
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AbstractList | Non-selective non-steroidal anti-inflammatory drugs (nNSAIDs) used in combination with warfarin are associated with an approximately 3-fold increased risk of upper gastrointestinal bleeding (UGIB) compared with warfarin alone. Celecoxib, a selective inhibitor of cyclo-oxygenase 2 (COX-2), is associated with less gastric mucosal injury and platelet dysregulation than nNSAIDs. We compared rates of bleeding complications in patients taking celecoxib and warfarin with those taking warfarin alone.PURPOSENon-selective non-steroidal anti-inflammatory drugs (nNSAIDs) used in combination with warfarin are associated with an approximately 3-fold increased risk of upper gastrointestinal bleeding (UGIB) compared with warfarin alone. Celecoxib, a selective inhibitor of cyclo-oxygenase 2 (COX-2), is associated with less gastric mucosal injury and platelet dysregulation than nNSAIDs. We compared rates of bleeding complications in patients taking celecoxib and warfarin with those taking warfarin alone.We performed a retrospective analysis using data from our Protime Clinic and pharmacy databases from January 2001 to April 2004. We identified 123 patients who took celecoxib and warfarin concurrently (overlap group). We compared rates of bleeding complications in this group with 1022 control patients who were taking warfarin alone. Bleeding complications were defined as major if they resulted in hospitalization, blood transfusion or death.SUBJECTS AND METHODSWe performed a retrospective analysis using data from our Protime Clinic and pharmacy databases from January 2001 to April 2004. We identified 123 patients who took celecoxib and warfarin concurrently (overlap group). We compared rates of bleeding complications in this group with 1022 control patients who were taking warfarin alone. Bleeding complications were defined as major if they resulted in hospitalization, blood transfusion or death.During approximately 1063 months of exposure to both celecoxib and warfarin, 10 bleeding complications were identified, only one of which was considered major. No patients had UGIB. In the control group, 116 bleeding complications were identified over approximately 16 520 months of exposure to warfarin alone, with 101 minor and 15 major events, including six episodes of UGIB. The relative risk of all bleeding complications was 1.34 (95% CI: 0.70-2.57) in the overlap vs. control groups, and for major bleeds was 1.04 (95% CI: 0.14-7.85).RESULTSDuring approximately 1063 months of exposure to both celecoxib and warfarin, 10 bleeding complications were identified, only one of which was considered major. No patients had UGIB. In the control group, 116 bleeding complications were identified over approximately 16 520 months of exposure to warfarin alone, with 101 minor and 15 major events, including six episodes of UGIB. The relative risk of all bleeding complications was 1.34 (95% CI: 0.70-2.57) in the overlap vs. control groups, and for major bleeds was 1.04 (95% CI: 0.14-7.85).There is a mild but non-significant increase in bleeding complications in patients taking celecoxib and warfarin compared with those taking warfarin alone.CONCLUSIONSThere is a mild but non-significant increase in bleeding complications in patients taking celecoxib and warfarin compared with those taking warfarin alone. Purpose: Non-selective non-steroidal anti-inflammatory drugs (nNSAIDs) used in combination with warfarin are associated with an approximately 3-fold increased risk of upper gastrointestinal bleeding (UGIB) compared with warfarin alone. Celecoxib, a selective inhibitor of cyclo-oxygenase 2 (COX-2), is associated with less gastric mucosal injury and platelet dysregulation than nNSAIDs. We compared rates of bleeding complications in patients taking celecoxib and warfarin with those taking warfarin alone. Subjects and Methods:We performed a retrospective analysis using data from our Protime Clinic and pharmacy databases from January 2001 to April 2004. We identified 123 patients who took celecoxib and warfarin concurrently (overlap group). We compared rates of bleeding complications in this group with 1022 control patients who were taking warfarin alone. Bleeding complications were defined as major if they resulted in hospitalization, blood transfusion or death. Results:During approximately 1063 months of exposure to both celecoxib and warfarin, 10 bleeding complications were identified, only one of which was considered major. No patients had UGIB. In the control group, 116 bleeding complications were identified over approximately 16 520 months of exposure to warfarin alone, with 101 minor and 15 major events, including six episodes of UGIB. The relative risk of all bleeding complications was 1.34 (95% CI: 0.70-2.57) in the overlap vs. control groups, and for major bleeds was 1.04 (95% CI: 0.14-7.85). Conclusions:There is a mild but non-significant increase in bleeding complications in patients taking celecoxib and warfarin compared with those taking warfarin alone. Non-selective non-steroidal anti-inflammatory drugs (nNSAIDs) used in combination with warfarin are associated with an approximately 3-fold increased risk of upper gastrointestinal bleeding (UGIB) compared with warfarin alone. Celecoxib, a selective inhibitor of cyclo-oxygenase 2 (COX-2), is associated with less gastric mucosal injury and platelet dysregulation than nNSAIDs. We compared rates of bleeding complications in patients taking celecoxib and warfarin with those taking warfarin alone. We performed a retrospective analysis using data from our Protime Clinic and pharmacy databases from January 2001 to April 2004. We identified 123 patients who took celecoxib and warfarin concurrently (overlap group). We compared rates of bleeding complications in this group with 1022 control patients who were taking warfarin alone. Bleeding complications were defined as major if they resulted in hospitalization, blood transfusion or death. During approximately 1063 months of exposure to both celecoxib and warfarin, 10 bleeding complications were identified, only one of which was considered major. No patients had UGIB. In the control group, 116 bleeding complications were identified over approximately 16 520 months of exposure to warfarin alone, with 101 minor and 15 major events, including six episodes of UGIB. The relative risk of all bleeding complications was 1.34 (95% CI: 0.70-2.57) in the overlap vs. control groups, and for major bleeds was 1.04 (95% CI: 0.14-7.85). There is a mild but non-significant increase in bleeding complications in patients taking celecoxib and warfarin compared with those taking warfarin alone. |
Author | Kearns, P. Bush, T. M. Chakravarty, E. F. Wang, C. Chung, L. |
Author_xml | – sequence: 1 givenname: L. surname: Chung fullname: Chung, L. organization: Division of Immunology and Rheumatology, Department of Medicine, Stanford University Hospital and Clinics, Stanford – sequence: 2 givenname: E. F. surname: Chakravarty fullname: Chakravarty, E. F. organization: Division of Immunology and Rheumatology, Department of Medicine, Stanford University Hospital and Clinics, Stanford – sequence: 3 givenname: P. surname: Kearns fullname: Kearns, P. organization: Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, USA – sequence: 4 givenname: C. surname: Wang fullname: Wang, C. organization: Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, USA – sequence: 5 givenname: T. M. surname: Bush fullname: Bush, T. M. organization: Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, USA |
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Keywords | Human Prostaglandin-endoperoxide synthase Warfarin Enzyme Coumarine derivatives Pesticides anticoagulation Enzyme inhibitor Anticoagulant Cyclooxygenase 2 inhibitor Celecoxib Rodenticide Hemorrhage bleeding complications Non steroidal antiinflammatory agent Antivitamin K Treatment Complication cyclo-oxygenase 2 inhibitor Oxidoreductases |
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Notes | The authors have no financial disclosures related to this manuscript. The results of this study were presented at the American College of Rheumatology meeting in October 2004 as a poster presentation. ArticleID:JCPT676 ark:/67375/WNG-BDN38HM8-9 istex:FC8D6E05566CC4109C144C6EADA330E4982877F1 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
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References | Guidelines ACoRSoRA (2002) Guidelines for the management of rheumatoid arthritis. Arthritis and Rheumatism, 46, 328-346. Battistella M, Mamdami M, Juurlink D, Rabeneck L, Laupacis A (2005) Risk of upper gastrointestinal hemorrhage in warfarin users treated wtih nonselective NSAIDs or COX-2 inhibitors. Archives of Internal Medicine, 165, 189-192. Levine M, Raskob G, Hirsh J (1989) Hemorrhagic complications of long-term anticoagulant therapy. Chest, 95, 26S-36S. Ray W, Stein C, Daugherty J, Hall K, Arbogast P, Griffin M (2002) COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet, 360, 1071-1073. Verbeeck R, Blackburn J, Loewen G (1983) Clinical pharmacokinetics of non-steroidal anti-inflammatory drugs. Clinical Pharmacokinetics, 8, 297-331. Bull S, Conell C, Campen D (2002) Relationship of clinical factors to the use of cox-2 selective NSAIDs within an arthritis population in a large HMO. Journal of Managed Care Pharmacy: JMCP, 8, 252-258. Mersfelder T, Stewart L (2000) Warfarin and celecoxib interaction. Annals of Pharmacotherapy, 34, 325-327. Errichetti A, Holden A, Ansell J (1984) Management of oral anticoagulant therapy. Archives of Internal Medicine, 144, 1966-1968. Manninen P, Riihimaki H, Heliovaara M, Makela P (1996) Overweight, gender and knee osteoarthritis. International Journal of Obesity and Related Metabolic Disorders, 20, 595-597. Linder J, Monkemuller K, Davis J, Wilcox C (2000) Cyclooxygenase-2 inhibitor celecoxib: a possible cause of gastropathy and hypoprothrombinemia. Southern Medical Journal, 93, 930-932. Kimmel S, Berlin J, Muredach R et al. (2005) Patients exposed to rofecoxib and celecoxib have different odds of nonfatal myocardial infarction. Annals of Internal Medicine, 142, 157-164. Serlin M, Breckenridge A (1983) Drug interactions with warfarin. Drugs, 2, 610-620. Solomon D, Schneeweiss S, Glynn R et al. (2004) Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation, 109, 2068-2073. Shorr R, Ray W, Daugherty J, Griffin M (1993) Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. Archives of Internal Medicine, 153, 1665-1670. Hernandez-Diaz S, Garcia-Rodriguez L (2001) Epidemiologic assessment of the safety of conventional nonsteroidal anti-inflammatory drugs. American Journal of Medicine, 110, 20S-27S. Silverstein F, Faich G, Goldstein J et al. (2000) Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis. Jama, 284, 1247-1255. Symmons D (2002) Epidemiology of rheumatoid arthritis: determinants of onset, persistence and outcome. Best Practice and Research. Clinical Rheumatology, 16, 707-722. Karim A, Tolbert D, Piergies A et al. (2000) Celecoxib does not significantly alter the pharmacokinetics or hypoprothrombinemic effect of warfarin in healthy subjects. Journal of Clinical Pharmacology, 40, 655-663. Mamdani M, Rochon P, Juurlink D et al. (2003) Effect of selective cyclooxygenase 2 inhibitors and naproxen on short-term risk of acute myocardial infarction in the elderly. Archives of Internal Medicine, 163, 481-486. Administration UFaD (1999) US Food and Drug Administration Safety Alert Available at: http://www.fda.gov/medwatch/safety/1999/celebr.htm. Chiquette E, Amato M, Bussey H (1998) Comparison of an anticoagulation clinic with usual medical care. Archives of Internal Medicine, 158, 1641-1647. Gutthann S, Garcia-Rodriguez L, Raiford D (1997) Individual nonsteroidal antiinflammatory drugs and other risk factors for upper gastrointestinal bleeding and perforation. Epidemiology, 8, 18-24. Lanza F (1998) A guideline for the treatment and prevention of NSAID-induced ulcers. American Journal of Gastroenterology, 93, 2037-2046. Carson J, Strom B, Soper K, West S, Morse M (1987) The association of nonsteroidal anti-inflammatory drugs with upper gastrointestinal tract bleeding. Archives of Internal Medicine, 147, 85-88. Simon L, Weaver A, Graham D et al. (1999) Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial. Jama, 282, 1921-1928. |
References_xml | – reference: Carson J, Strom B, Soper K, West S, Morse M (1987) The association of nonsteroidal anti-inflammatory drugs with upper gastrointestinal tract bleeding. Archives of Internal Medicine, 147, 85-88. – reference: Silverstein F, Faich G, Goldstein J et al. (2000) Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis. Jama, 284, 1247-1255. – reference: Linder J, Monkemuller K, Davis J, Wilcox C (2000) Cyclooxygenase-2 inhibitor celecoxib: a possible cause of gastropathy and hypoprothrombinemia. Southern Medical Journal, 93, 930-932. – reference: Levine M, Raskob G, Hirsh J (1989) Hemorrhagic complications of long-term anticoagulant therapy. Chest, 95, 26S-36S. – reference: Lanza F (1998) A guideline for the treatment and prevention of NSAID-induced ulcers. American Journal of Gastroenterology, 93, 2037-2046. – reference: Mamdani M, Rochon P, Juurlink D et al. (2003) Effect of selective cyclooxygenase 2 inhibitors and naproxen on short-term risk of acute myocardial infarction in the elderly. Archives of Internal Medicine, 163, 481-486. – reference: Verbeeck R, Blackburn J, Loewen G (1983) Clinical pharmacokinetics of non-steroidal anti-inflammatory drugs. Clinical Pharmacokinetics, 8, 297-331. – reference: Serlin M, Breckenridge A (1983) Drug interactions with warfarin. Drugs, 2, 610-620. – reference: Bull S, Conell C, Campen D (2002) Relationship of clinical factors to the use of cox-2 selective NSAIDs within an arthritis population in a large HMO. Journal of Managed Care Pharmacy: JMCP, 8, 252-258. – reference: Ray W, Stein C, Daugherty J, Hall K, Arbogast P, Griffin M (2002) COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet, 360, 1071-1073. – reference: Simon L, Weaver A, Graham D et al. (1999) Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial. Jama, 282, 1921-1928. – reference: Guidelines ACoRSoRA (2002) Guidelines for the management of rheumatoid arthritis. Arthritis and Rheumatism, 46, 328-346. – reference: Hernandez-Diaz S, Garcia-Rodriguez L (2001) Epidemiologic assessment of the safety of conventional nonsteroidal anti-inflammatory drugs. American Journal of Medicine, 110, 20S-27S. – reference: Chiquette E, Amato M, Bussey H (1998) Comparison of an anticoagulation clinic with usual medical care. Archives of Internal Medicine, 158, 1641-1647. – reference: Administration UFaD (1999) US Food and Drug Administration Safety Alert Available at: http://www.fda.gov/medwatch/safety/1999/celebr.htm. – reference: Gutthann S, Garcia-Rodriguez L, Raiford D (1997) Individual nonsteroidal antiinflammatory drugs and other risk factors for upper gastrointestinal bleeding and perforation. Epidemiology, 8, 18-24. – reference: Kimmel S, Berlin J, Muredach R et al. (2005) Patients exposed to rofecoxib and celecoxib have different odds of nonfatal myocardial infarction. Annals of Internal Medicine, 142, 157-164. – reference: Shorr R, Ray W, Daugherty J, Griffin M (1993) Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. Archives of Internal Medicine, 153, 1665-1670. – reference: Manninen P, Riihimaki H, Heliovaara M, Makela P (1996) Overweight, gender and knee osteoarthritis. International Journal of Obesity and Related Metabolic Disorders, 20, 595-597. – reference: Karim A, Tolbert D, Piergies A et al. (2000) Celecoxib does not significantly alter the pharmacokinetics or hypoprothrombinemic effect of warfarin in healthy subjects. Journal of Clinical Pharmacology, 40, 655-663. – reference: Symmons D (2002) Epidemiology of rheumatoid arthritis: determinants of onset, persistence and outcome. Best Practice and Research. Clinical Rheumatology, 16, 707-722. – reference: Battistella M, Mamdami M, Juurlink D, Rabeneck L, Laupacis A (2005) Risk of upper gastrointestinal hemorrhage in warfarin users treated wtih nonselective NSAIDs or COX-2 inhibitors. Archives of Internal Medicine, 165, 189-192. – reference: Errichetti A, Holden A, Ansell J (1984) Management of oral anticoagulant therapy. Archives of Internal Medicine, 144, 1966-1968. – reference: Solomon D, Schneeweiss S, Glynn R et al. (2004) Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation, 109, 2068-2073. – reference: Mersfelder T, Stewart L (2000) Warfarin and celecoxib interaction. Annals of Pharmacotherapy, 34, 325-327. |
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Title | Bleeding complications in patients on celecoxib and warfarin |
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