Tegaserod is Effective in the Initial and Retreatment of IBS-C
Please note: The following announcement supersedes any information contained in this article. On March 30, 2007, Novartis, in compliance with an FDA request, suspended marketing and sales of its irritable bowel/constipation drug tegaserod maleate (Zelnorm) after an analysis of its clinical database pointed to a higher incidence of myocardial infarction, stroke, and unstable angina among patients taking the drug. For updated information on this issue, see the Medscape Alert Center on tegaserod.

Summary and Introduction

Summary

Background: Symptoms of irritable bowel syndrome are often cyclical and thus may require repeated rather than continuous therapy. Tegaserod is effective and well-tolerated for irritable bowel syndrome with constipation but data on retreatment are lacking.
Aim: To assess whether tegaserod retreatment is as efficacious and well-tolerated as initial treatment in a primary care setting.
Methods: This open-label trial was designed to evaluate the effectiveness of tegaserod under real-life conditions. Irritable bowel syndrome with constipation patients received tegaserod 6 mg b.d. for 12 weeks; response was assessed at weeks 4 and 12. Responders (those achieving satisfactory relief for at least 2 of the previous 4 weeks) at weeks 4 and/or 12 entered an 8-week withdrawal period where symptom recurrence was assessed. Patients experiencing recurrence could receive tegaserod 6 mg b.d. for another 4 weeks (retreatment phase) and on completion, could choose to continue tegaserod in a 6-month extension study.
Results: A total of 513 patients received initial treatment with tegaserod; 85.0% (436 of 513) responded. 403 responders entered the withdrawal period; symptoms recurred in 83.9% (338 of 403) after a mean of 38 days. Of the 307 patients who subsequently entered retreatment 89.3% (274 of 307) responded. Among patients entering the retreatment period, 269 (87.6%) had responded within the first 4 weeks of initial treatment. Of these, 243 (90.3%) responded to tegaserod retreatment. Adverse events were infrequent and similar during 4 weeks of the initial treatment period (11.1%) and on retreatment (10.4%). The extension study, completed by 188 of 232 (81.0%) patients, demonstrated good long-term tolerability of tegaserod.
Conclusions: Irritable bowel syndrome with constipation patients can be successfully treated, and retreated, with tegaserod 6 mg b.d. Tegaserod was well-tolerated during initial and retreatment periods.

Irritable bowel syndrome (IBS) is a chronic and recurrent symptomatic gastrointestinal (GI) disorder that is characterized by abdominal pain/discomfort, bloating and altered bowel function such as constipation (IBS-C) or diarrhoea. In general, IBS is a chronic condition with fluctuations in intensity in many patients. In the absence of treatment, IBS symptoms appear to occur over time in clusters rather than random individual symptoms occurring alone. Because of the episodic nature of IBS, patients often require repeated courses of treatment. Therefore, it is important that pharmacological interventions can be used repeatedly without a deterioration of efficacy.

Tegaserod is a selective 5-HT₄-receptor partial agonist that helps to normalize GI tract function by activating 5-HT₄-receptors, which are located primarily on enteric ganglia and smooth muscle cells. Tegaserod stimulates the release of enteric neurotransmitters resulting in enhanced intestinal secretion, stimulation of the peristaltic reflex and increased contractility. Tegaserod also augments peristaltic and secretory reflexes and inhibits visceral afferent responses involved in pain signal transmission to the central nervous system.

In large, randomized, placebo-controlled studies, tegaserod has been shown to be effective in treating patients with IBS-C. Tegaserod normalized bowel habit and relieved the multiple symptoms associated with IBS-C: abdominal pain/discomfort, bloating and constipation. In these studies, tegaserod was well tolerated. The long-term (12-month) safety and tolerability of tegaserod has also been demonstrated in patients with IBS-C. A number of recent studies have investigated the post-treatment withdrawal characteristics of tegaserod. Following withdrawal, a loss of treatment effect and symptom recurrence was observed. However, recurring symptoms were, on average, not as severe as those experienced at baseline.

Although the efficacy and tolerability of retreating patients previously withdrawn from tegaserod treatment has not been widely studied, a recent study established that patients who were retreated with tegaserod following a withdrawal period subsequently experienced symptom relief similar to that seen with initial treatment.

The present, open-label study was designed to assess whether retreatment with tegaserod in patients experiencing symptom recurrence following treatment withdrawal was as efficacious and well-tolerated as the initial 12-week course of treatment. The study had an open-label design and enrolled patients from a primary care setting, aiming to reflect as closely as possible the use of tegaserod in a 'real-life' clinical situation and the cyclical nature of IBS. In addition, the long-term tolerability of tegaserod treatment was assessed during an optional 6-month extension study.