teaser
Carole Mongin-Bulewski
PhD
Editor
Hospital Pharmacy Europe
IBS (irritable bowel syndrome) is a common but uncomfortable disorder of the colon or rectum. While the basic cause of IBS is unknown, it has been found that the colon muscle in people with IBS contracts more readily than in people without IBS. A number of factors can “trigger” IBS, including certain foods and medicines, as well as emotional stress. IBS is not a life-threatening condition and does not make a person more likely to develop other colon conditions, such as colitis, Crohn’s disease or colon cancer.
IBS is a chronic, relapsing condition encompassing a wide variety of gastrointestinal (GI) symptoms.Symptoms of IBS include:
- Abdominal pains or cramps (usually in the lower half of the abdomen).
- Excess gas.
- Harder or looser bowel movements than average.
Symptoms of IBS do not include bleeding or black stools.
A new drug treatment for IBS
Current drug treatments for IBS are of limited value, and many treatments target specific symptoms. Tegaserod, a 5-HT(4)-receptor partial agonist, has a novel mechanism of action in the treatment of IBS.(1)
Tegaserod is a drug in a new class of compounds called aminoguanidine indoles, and it is structurally similar to serotonin (5-HT), with modifications that make the drug selective for the 5-HT(4) receptor.
A Cochrane review evaluated the efficacy and tolerability of tegaserod in the treatment of IBS in patients 12 years of age and older.(2) Randomised or quasi-randomised controlled trials comparing tegaserod with placebo, no treatment or any other intervention (pharmacological or nonpharmacological) in subjects aged 12 years and above with a diagnosis of IBS focusing on clinical endpoints were considered for review. Eight short-term placebo-controlled studies fulfilled the inclusion criteria. These were mainly conducted in women. Seven studies evaluated the efficacy of tegaserod on global GI symptoms in patients with constipation-predominant IBS, and one small study evaluated safety in patients with diarrhoea-predominant IBS.
Compared with patients receiving placebo, the relative risk (RR) of responding in terms of global relief of GI symptoms was significantly higher in patients who received tegaserod in dosages of 12mg per day (RR 1.19; 95% CI 1.09–1.29) and 4mg per day (RR 1.15; 95% CI 1.02–1.31), with numbers needed to treat (NNT) of 14 and 20, respectively. Comparision of patients who received tegaserod at any dosage (n=4,040) with patients who received placebo showed that the RR of responding was 1.17 (95% CI 1.08–1.27), with an NNT of 17. The pooled results indicate a statistically significant benefit with tegaserod, but the a-priori minimal clinically important differences that were set in two of the four pooled studies were not reached. Tegaserod did not significantly improve patients’ individual symptoms of abdominal pain and discomfort, but a statistically significant improvement in bowel habits was observed in patients in the lower dosage group. There was a nonsignificant trend in favour of the 12mg dosage.
Separate assessment of GI symptoms showed that symptoms indicative of GI motility, such as number of bowel movements and days without bowel movements, were generally improved in patients who received tegaserod, although the proportion of patients experiencing diarrhoea was significantly higher in the 12mg group than in the placebo group (RR 2.75; 95% CI 1.90–3.97), with a number needed to harm (NNH) of 20. The effects of tegaserod on GI symptoms such as bloating, stool consistency and straining were not consistent across the studies.
Tegaserod was well tolerated by most patients, with the most common side-effect being diarrhoea.(3,4) Headache, abdominal pain and nausea were experienced with increased frequency, but this was not statistically significant. No cardiac effects were observed, as is the case with other partial 5-HT(4)-receptor agonist GI-motility agents.
In a recent open-label trial designed to evaluate the effectiveness of tegaserod under real-life conditions, constipation-predominant IBS patients received tegaserod 6mg twice daily for 12 weeks.(5) Response was assessed at weeks 4 and 12. Responders (who were defined as those achieving satisfactory relief for at least two of the previous four weeks) at weeks 4 and/or 12 entered an eight-week withdrawal period where symptom reccurence was assessed. Patients experiencing recurrence received tegaserod 6mg twice daily for another four weeks and, on completion, could choose to continue tegaserod in a six-month extension study. Among the 513 patients who received initial treatment, 85% (n=436) responded, of which 403 entered the withdrawal period. Symptoms recurred in 83.9% of patients after 38 days in average. Of the 307 patients who subsequently entered retreatment, 89.3% responded, with 87.6% responding within the first four weeks of initial treatment. Among these, 90.3% responded to retreatment. Side-effects were infrequent and similar during four weeks of the initial treatment period (11.1%) and on retreatment (10.4%). Finally, the extension study, which was completed by 81% of patients, demonstrated good long-term tolerability.
Conclusion
Few data are available about the efficacy of tegaserod in men and its impact on quality of life. Longer-term studies are needed to determine the duration of treatment and the safety of this drug with prolonged used. However, it can be used for short-term relief of global GI symptoms in women with constipation-predominant IBS, although it does not affect their abdominal pain and discomfort.
References
- Patel S, Berrad D, Lembo A. Review of tegaserod in the treatment of irritable bowel syndrome. Expert Opin Pharmacother 2004;5:2369-79.
- Evans BW, Clark WK, Moore DJ, Whorwell PJ. Tegaserod for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev 2004:CD003960.
- Schoenfeld P. Review article: the safety profile of tegaserod. Aliment Pharmacol Ther 2004;20 Suppl:25-30.
- Hasler WL, Schoenfeld P. Safety profile of tegaserod, a 5-HT4 receptor agonist, for the treatment of irritable bowel syndrome. Drug Saf 2004;27:619-31.
- Müller-Lissner S, Holtmann G, Ruegg P, et al. Tegaserod is effective in the initial and retreatment of irritable bowel syndrome with constipation. Aliment Pharmacol Ther 2005;21:11-20.
