SAFETY AND EFFICACY OF TEGASEROD THERAPY IN PATIENTS WITH IRRITABLE BOWEL SYNDROME OR CHRONIC CONSTIPATION
Main Article Content
Keywords
Tegaserod, irritable bowel syndrome, chronic constipation
Abstract
Background
Tegaserod, a 5-HT4 agonist, is effective for treating irritable bowel syndrome and chronic constipation. However, sales of this drug were recently suspended due to concerns about a higher rate of cardiovascular events in patients receiving tegaserod over placebo in clinical trials. Our aim was to review patients in our practice prescribed tegaserod to determine if any of them had suffered a cardiovascular event or other significant adverse effects while on this therapy. Additionally, we attempted to determine the efficacy of tegaserod in clinical practice.
Methods
Patients with irritable bowel syndrome or chronic constipation in our practice prescribed tegaserod were identified through a search of billing codes and charts reviews. These patients were contacted and questioned about symptoms of cardiovascular events or other adverse events while on tegaserod. The efficacy of this drug was determined by a symptom scale during and after stopping tegaserod.
Results
Sufficient data for analysis was retrieved for 51 of 67 patients prescribed tegaserod. Of these, 37 patients (72.5%) experience no adverse events and 14 patients (27.4%) experienced at least one adverse event, including 6 patients (11.8%) with major adverse events (2 patients (3.9%) with atypical chest pain; 4 patients (7.8%) with syncope; and 2 patients (3.9%) who died. One patient died from advanced pancreatic cancer. The other, who had multiple cardiovascular risk factors as well as a previous myocardial infarction, suffered a cardiac arrest 2 days postoperatively following a below knee amputation, and had actually been off tegaserod for 7 days after hospital admission. Patients graded the severity of both abdominal pain and constipation as worse after stopping therapy compared to during therapy (p<0.0002 and p<0.0001, respectively).
Conclusions
The risk of cardiovascular events during tegaserod therapy may be increased in patients with other risk factors. However, this drug is effective for treating irritable bowel syndrome and chronic constipation, and might be used in a select patient population with severe symptoms but without other risk factors for cardiovascular events.
References
2. Drossman DA, Li Z, Andruzzi E, et al. U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact. Dig Dis Sci 1993 Sep;38(9):1569-80.
3. Brandt LJ, Bjorkman D, Fennerty MB, et al. Systematic review on the management of irritable bowel syndrome in North America. Am J Gastroenterol 2002 Nov;97(11 Suppl):S7-26.
4. Hahn BA, Saunders WB, Maier WC. Differences between individuals with self-reported irritable bowel syndrome (IBS) and IBS-like symptoms. Dig Dis Sci 1997 Dec;42(12):2585-90.
5. Saito YA, Locke GR, Talley NJ, Zinsmeister AR, Fett SL, Melton LJ, 3rd. A comparison of the Rome and Manning criteria for case identification in epidemiological investigations of irritable bowel syndrome. Am J Gastroenterol 2000 Oct;95(10):2816-24.
6. Thompson WG, Irvine EJ, Pare P, Ferrazzi S, Rance L. Functional gastrointestinal disorders in Canada: first population-based survey using Rome II criteria with suggestions for improving the questionnaire. Dig Dis Sci 2002 Jan;47(1):225-35.
7. Hungin AP, Whorwell PJ, Tack J, Mearin F. The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40,000 subjects. Aliment Pharmacol Ther 2003 Mar 1;17(5): 643-50.
8. Schuster MM. Diagnostic evaluation of the irritable bowel syndrome. Gastroenterol Clin North Am 1991 Jun;20(2):269-78.
9. Farthing MJ. Irritable bowel syndrome: new pharmaceutical approaches to treatment. Baillieres Best Pract Res Clin Gastroenterol 1999 Oct;13(3):461-71.
10. Wald A. Irritable Bowel Syndrome. Curr Treat Options Gastroenterol 1999 Feb;2(1):13-9.
11. Serra J, Azpiroz F,Malagelada JR. Impaired transit and tolerance of intestinal gas in the irritable bowel syndrome. Gut 2001 Jan;48(1):14-9.
12. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology 2006 Apr;130(5):1480-91.
13. Stewart WF, Liberman JN, Sandler RS, et al. Epidemiology of constipation (EPOC) study in the United States: relation of clinical subtypes to sociodemographic features. Am J Gastroenterol 1999 Dec;94(12):3530-40.
14. Sonnenberg A, Koch TR. Physician visits in the United States for constipation: 1958 to 1986. Dig Dis Sci 1989 Apr;34(4):606-11.
15. Pare P, Ferrazzi S, Thompson WG, Irvine EJ, Rance L. An epidemiological survey of constipation in canada: definitions, rates, demographics, and predictors of health care seeking. Am J Gastroenterol 2001 Nov;96(11):3130-7.
16. Heaton KW, Radvan J, Cripps H, Mountford RA, Braddon FE, Hughes AO. Defecation frequency and timing, and stool form in the general population: a prospective study. Gut 1992 Jun;33(6): 818-24.
17. Johanson JF, Sonnenberg A, Koch TR. Clinical epidemiology of chronic constipation. J Clin Gastroenterol 1989 Oct;11(5):525-36.
18. Everhart JE, Go VL, Johannes RS, Fitzsimmons SC, Roth HP, White LR. A longitudinal survey of self-reported bowel habits in the United States. Dig Dis Sci 1989 Aug;34(8):1153-62.
19. Sandler RS, Drossman DA. Bowel habits in young adults not seeking health care. Dig Dis Sci 1987 Aug;32(8):841-5.
20. Koch A, Voderholzer WA, Klauser AG, Muller- Lissner S. Symptoms in chronic constipation. Dis Colon Rectum 1997 Aug;40(8):902-6.
21. American College of Gastroenterology Chronic Constipation Task Force. An evidence-based approach to the management of chronic constipation in North America. Am J Gastroenterol 2005;100 Suppl 1:S1-4.
22. Gershon MD. Serotonin and its implication for the management of irritable bowel syndrome. Rev Gastroenterol Disord 2003;3 Suppl 2:S25-34.
23. Evans BW, Clark WK, Moore DJ, Whorwell PJ. Tegaserod for the treatment of irritable bowel syndrome and chronic constipation. Cochrane Database Syst Rev 2007(4):CD003960.
24. Lembo A, Camilleri M. Chronic constipation. N Engl JMed 2003 Oct 2;349(14):1360-8.
25. FDA Announces Discontinued Marketing of GI Drug, Zelnorm, for Safety Reasons FDA; March 30 ,2007 [cited 2009 May,21 ]; Available from: http://www.fda.gov/bbs/topics/NEWS/2007/NEW 01597.html.
26. FDA Permits Restricted Use of Zelnorm for Qualifying Patients July 27, 2007 [cited 2009 May 21]; Available from: http://www.fda.gov/bbs/topics/NEWS/2007/NEW 01673.html.
27. Tack J, Muller-Lissner S, Bytzer P, et al. A randomised controlled trial assessing the efficacy and safety of repeated tegaserod therapy in women with irritable bowel syndrome with constipation. Gut 2005 Dec;54(12):1707-13.
28. Fock KM, Wagner A. Safety, tolerability and satisfaction with tegaserod therapy in Asia-Pacific patients with irritable bowel syndrome with constipation. J Gastroenterol Hepatol 2007 Aug;22(8): 1190-8.
29. Morganroth J, Ruegg PC, Dunger-Baldauf C, Appel-Dingemanse S, Bliesath H, Lefkowitz M. Tegaserod, a 5-hydroxytryptamine type 4 receptor partial agonist, is devoid of electrocardiographic effects. Am J Gastroenterol 2002 Sep;97(9):2321- 7.
30. Anderson JL, May HT, Bair TL, Muhlestein JB, Horne BD, Carlquist JF. Lack of association of tegaserod with adverse cardiovascular outcomes in a matched case-control study. J Cardiovasc
Pharmacol Ther 2009 Sep;14(3):170-5.
31. Johanson JF, Wald A, Tougas G, et al. Effect of tegaserod in chronic constipation: a randomized, double-blind, controlled trial. Clin Gastroenterol Hepatol 2004 Sep;2(9):796-805.
32. Kamm MA, Muller-Lissner S, Talley NJ, et al. Tegaserod for the treatment of chronic constipation: a randomized, double-blind, placebocontrolled multinational study. Am J Gastroenterol 2005 Feb;100(2):362-72.
33. Schoenfeld P. Review article: the safety profile of tegaserod. Aliment Pharmacol Ther 2004 Nov;20 Suppl 7:25-30.
34. Camilleri M. Review article: tegaserod. Aliment Pharmacol Ther 2001 Mar;15(3):277-89.