Correspondence
Gastropathy Due to Celecoxib, a Cyclooxygenase-2 Inhibitor
N Engl J Med 1999; 340:2005-2006June 24, 1999
- Article
To the Editor:
Celecoxib (Celebrex), a cyclooxygenase (COX)-2–specific nonsteroidal antiinflammatory drug (NSAID), was recently introduced in the U.S. market. COX-2 is induced in inflammation, whereas COX-1 produces protective prostaglandins in the stomach. Because of its specificity for COX-2, celecoxib is less likely to cause gastric injury. A one-week endoscopic study of gastrointestinal mucosal effects in phase 2 trials showed that gastric ulcers developed in 19 percent of the subjects receiving naproxen, whereas no ulcers developed in the subjects receiving celecoxib or placebo.1 We describe a patient in whom NSAID-induced gastropathy developed while she was taking celecoxib.
A 69-year-old woman presented with abdominal cramps. She was found to have antibodies to Helicobacter pylori and was treated with lansoprazole, amoxicillin, and clarithromycin eight weeks before presentation. She had been treated with tramadol for arthritis; the medication was switched to celecoxib, in doses of 100 mg twice a day, six weeks before presentation. While the patient was taking celecoxib, severe epigastric pain developed. Another two-week course of treatment for H. pylori was given four weeks before presentation. She was referred to us since the epigastric pain persisted. Esophagogastroduodenoscopy revealed severe, erosive gastropathy with multiple petechial hemorrhages and small erosions involving the body and antrum. Histologically, no inflammation was seen in the body, and slight inflammation was seen in the antrum, findings compatible with NSAID-induced gastropathy. H. pylori was not identified. Treatment with celecoxib was discontinued, and the patient was given 40 mg of omeprazole by mouth twice a day for a week and then once a day. The burning abdominal pain resolved in a week.
NSAIDs with COX-2 selectivity had antiinflammatory effects in mice only at doses at which they inhibited COX-1.2 At these doses, they inhibited gastric prostaglandin synthesis and elicited gastric erosions. COX-2 was induced in the stomach after injury, and COX-2 inhibitors impaired the healing of ulcers in mice.3 This finding implies a role for gastric prostaglandins derived from COX-2 in mucosal resistance to injury. COX-2 was localized in the base of gastric ulcers in rats, which suggests a role for COX-2 in the healing of ulcers.4 Even though celecoxib was not tested in these studies, the results raise the possibility of gastric mucosal injury with COX-2 inhibitors. This case report indicates that COX-2 inhibitors can cause gastric mucosal damage. The gastropathy was endoscopically and histologically characteristic of NSAID-induced gastropathy. Physicians should be aware of the potential for gastric injury with COX-2 inhibitors.
4 ReferencesSuneel Mohammed, M.D.
Dorwyn W. Croom, II, M.D.
Grace Health Care System, Morganton, NC 286551
Simon LS ,Lanza FL ,Lipsky PE , et al. Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor: efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects. Arthritis Rheum 1998;41:1591-1602
CrossRef | Web of Science | Medline2
Wallace JL ,Bak A ,McKnight W ,Asfaha S ,Sharkey KA ,MacNaughton WK . Cyclooxygenase 1 contributes to inflammatory responses in rats and mice: implications for gastrointestinal toxicity. Gastroenterology 1998;115:101-109
CrossRef | Web of Science | Medline3
Mizuno H ,Sakamoto C ,Matsuda K , et al. Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice. Gastroenterology 1997;112:387-397
CrossRef | Web of Science | Medline4
Takahashi S ,Shigeta J ,Inoue H ,Tananbe T ,Okabe S . Localization of cyclooxygenase-2 and regulation of its mRNA expression in gastric ulcers in rats. Am J Physiol 1998;275:G1137-G1145
Web of Science | Medline
- Citing Articles (19)
Citing Articles
1
Jeremy R. Parfitt, David K. Driman. (2007) Pathological effects of drugs on the gastrointestinal tract: a review. Human Pathology 38:4, 527-536
CrossRef2
2006. COX-2 inhibitors. , 1000-1015.
CrossRef3
Chengzhong Xing, Shunji Kato, Norio Matsukura, Noriko Matsuda, Huimian Xu, En Takashi, Nobutaka Yamada, Zenya Naito, Takashi Tajiri. (2005) Interleukin-8, Cyclo-oxygenase-2, and Trefoil Factor Family 1 Gene Expression and Their Association with Helicobacter pylori Infection in the Remnant Stomach. Surgery Today 35:12, 1026-1032
CrossRef4
Deborah Layton, Lynda V. Wilton, Saad A. W. Shakir. (2004) Safety profile of celecoxib as used in general practice in England: results of a prescription-event monitoring study. European Journal of Clinical Pharmacology 60:7, 489-501
CrossRef5
Johanne Martel-Pelletier, Jean-Pierre Pelletier, Hassan Fahmi. (2003) Cyclooxygenase-2 and prostaglandins in articular tissues. Seminars in Arthritis and Rheumatism 33:3, 155-167
CrossRef6
Julia Kirchheiner, Elke St??rmer, Christian Meisel, Nadine Steinbach, Ivar Roots, J??rgen Brockm??ller. (2003) Influence of CYP2C9 genetic polymorphisms on pharmacokinetics of celecoxib and its metabolites. Pharmacogenetics 13:8, 473-480
CrossRef7
Jane E. Weder, Carolyn T. Dillon, Trevor W. Hambley, Brendan J. Kennedy, Peter A. Lay, J.Ray Biffin, Hubert L. Regtop, Neal M. Davies. (2002) Copper complexes of non-steroidal anti-inflammatory drugs: an opportunity yet to be realized. Coordination Chemistry Reviews 232:1-2, 95-126
CrossRef8
Robert W. McMurray, Kenneth J. Hardy. (2002) Cox-2 Inhibitors:. The American Journal of the Medical Sciences 323:4, 181-189
CrossRef9
Pamela A. Foral, Amy F. Wilson, Kelly K. Nystrom. (2002) Gastrointestinal Bleeds Associated with Rofecoxib. Pharmacotherapy 22:3, 384-386
CrossRef10
K Rainsford. (2001) The ever-emerging anti-inflammatories. Have there been any real advances?. Journal of Physiology-Paris 95:1-6, 11-19
CrossRef11
Cuyue Tang, Magang Shou, Thomas H. Rushmore, Qin Mei, Punam Sandhu, Eric J. Woolf, Mark J. Rose, Alyssa Gelmann, Howard E. Greenberg, Inge De Lepeleire, Anne Van Hecken, Paul J. De Schepper, David L. Ebel, Jules I. Schwartz, A. David Rodrigues. (2001) In-vitro metabolism of celecoxib, a cyclooxygenase-2 inhibitor, by allelic variant forms of human liver microsomal cytochrome P450 2C9: correlation with CYP2C9 genotype and in-vivo pharmacokinetics. Pharmacogenetics 11:3, 223-235
CrossRef12
Neal M Davies, Thijs W Gudde, Martijn AWC de Leeuw. (2001) Celecoxib: a new option in the treatment of arthropathies and familial adenomatous polyposis. Expert Opinion on Pharmacotherapy 2:1, 139-152
CrossRef13
S Yedgar. (2000) Inhibition of phospholipase A2 as a therapeutic target. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1488:1-2, 182-187
CrossRef14
N S Buttar, K K Wang. (2000) The "aspirin" of the new millennium: cyclooxygenase-2 inhibitors.. Mayo Clinic Proceedings 75:10, 1027-1038
CrossRef15
Colette Hawkins, Geoffrey W Hanks. (2000) The Gastroduodenal Toxicity of Nonsteroidal Anti-Inflammatory Drugs. A Review of the Literature. Journal of Pain and Symptom Management 20:2, 140-151
CrossRef16
Neal M. Davies, Andrew J. McLachlan, Ric O. Day, Kenneth M. Williams. (2000) Clinical Pharmacokinetics and Pharmacodynamics of Celecoxib. Clinical Pharmacokinetics 38:3, 225-242
CrossRef17
Vincent C. Dennis, Brian K. Thomas, James E. Hanlon. (2000) Potentiation of Oral Anticoagulation and Hemarthrosis Associated with Nabumetone. Pharmacotherapy 20:2, 234-239
CrossRef18
G. Klein, W. Kullich. (2000) Short-Term Treatment of Painful Osteoarthritis of the Knee with Oral Enzymes. Clinical Drug Investigation 19:1, 15-23
CrossRef19
&NA;. (1999) Celecoxib. Reactions Weekly &NA;:758, 7
CrossRef
