Tegaserod: long-term treatment for irritable bowel syndrome patients with constipation in primary care.

BACKGROUND: Tegaserod, a prokinetic 5-HT4 receptor agonist, has demonstrated efficacy and tolerability in irritable bowel syndrome (IBS) patients with constipation (IBS-C) in controlled clinical trials. Its use in primary care has not been investigated. AIM: To determine whether tegaserod is effective and well tolerated by primary care IBS-C patients. METHODS: Patients received tegaserod 6 mg b.i.d. for 12 weeks and were assessed for response, abdominal pain/discomfort, bloating, stool consistency/frequency and straining at weeks 4 and 12. Previous successful treatment with the withdrawn drug, cisapride, was noted. A 9-month study extension was offered to patients completing 12 weeks of tegaserod treatment. RESULTS: 212 patients entered the 12-week treatment period; 166 completed as planned. Response rates were 64.2% at week 4 and 70.3% at week 12. After 12 weeks, abdominal pain/discomfort and bloating were reduced from baseline (p < 0.0001; mean change -1.02 and -0.91 points, respectively), stool frequency increased (0.78-0.97 stools/day) and stool consistency improved (2.45-3.42; lumpy stools became softer). Tegaserod was well tolerated; the most common adverse events were headache (13.2%) and diarrhea (9.4%). One hundred and twenty patients entered the 9-month extension study, 85 completed and tegaserod continued to be well tolerated. CONCLUSIONS: In ambulatory primary care IBS-C patients, tegaserod is an effective and well-tolerated long-term treatment.

Tegaserod, a 5-hydroxytryptamine type 4 receptor partial agonist, is devoid of electrocardiographic effects.

OBJECTIVES: Certain GI prokinetic agents have been shown to affect cardiac repolarization, which may be associated with life-threatening arrhythmias. The selective 5-hydroxytryptamine type 4 receptor partial agonist tegaserod is a novel promotile agent developed for the treatment of functional motility disorders such as irritable bowel syndrome (IBS). The aim of the study was to investigate the cardiac safety profile of tegaserod through analysis of electrocardiographic data from clinical studies conducted in patients with IBS and a study conducted in healthy male subjects. METHODS: In three randomized, double blind, placebo-controlled, parallel group clinical studies, 2516 IBS patients with symptoms of abdominal pain and constipation received tegaserod 2 or 6 mg b.i.d. (n = 1679) or placebo (n = 837) for 12 wk. In an additional study, 36 healthy male subjects received iv. single doses of tegaserod (0.8 mg to 20 mg) or placebo. Standard 12-lead electrocardiograms were recorded at baseline and during treatment. Baseline values were compared with data collected during the treatment period. RESULTS: The proportion of patients with prolongation of the QTc interval was the same for placebo and tegaserod, as was the frequency of overall electrocardiographic abnormalities. No ventricular or supraventricular tachycardia was observed. Comparable electrocardiographic results were obtained during placebo and tegaserod treatment. In healthy volunteers, tegaserod at i.v. doses resulting in plasma concentrations up to 100 times those measured after therapeutic doses (6 mg b.i.d.) did not influence electrocardiographic parameters. CONCLUSIONS: Tegaserod is devoid of electrocardiographic effects and is not expected to adversely influence cardiac function. These data confirm preclinical findings.

Safety and tolerability of tegaserod in patients with irritable bowel syndrome and diarrhea symptoms.

OBJECTIVES: Tegaserod is a selective serotonin (5-HT4) receptor partial agonist effective in providing relief from abdominal pain, bloating, and constipation in patients with irritable bowel syndrome. Tegaserod therapy may be associated with early transient diarrhea, which is related to its mechanism of action. This study was performed in patients with irritable bowel syndrome and symptoms of diarrhea to further assess the safety of tegaserod. METHODS: After a 2-wk baseline, patients were randomized (2:2:1) in a double-blind manner to receive 4 mg of tegaserod a day (n = 35), 12 mg of tegaserod a day (n = 34), or placebos (n = 17) for 8 wk. Patients had to fulfill > or =2 Rome diarrhea criteria > or =25% of the time. Adverse events were recorded. RESULTS: Diarrhea, abdominal pain, headache, flatulence, and fatigue were the most frequently reported adverse events. The frequency rates of diarrhea were 49%, 18%, and 35% for the 4 mg/day, 12 mg/day, and placebo groups, respectively; when the tegaserod data were pooled, the frequency of diarrhea was similar to that of the placebo group (33% and 35%, respectively). No complications of diarrhea (e.g., dehydration and electrolyte abnormalities) were reported. Five patients (6%), all from the tegaserod groups, discontinued study participation because of diarrhea and/or abdominal pain. No serious adverse events were reported. CONCLUSIONS: In this study, tegaserod at doses of 4 and 12 mg/day was safe and not associated with complications of diarrhea or serious adverse events.