Review article: the safety profile of tegaserod

Summary Gastrointestinal symptoms are the most common side‐effects of tegaserod therapy. In data pooled from Phase III randomized controlled trials in patients with irritable bowel syndrome with constipation, diarrhoea was reported by 8.8% of patients treated with tegaserod 6 mg b.d. vs. 3.8% of patients treated with placebo. Similar rates were observed in international post‐US marketing randomized controlled trials. In most patients, tegaserod‐induced diarrhoea was mild and transient. In randomized controlled trials, it did not elicit fluid or electrolyte disturbances, and fewer than 3% of irritable bowel syndrome patients discontinued tegaserod due to diarrhoea. The incidence of other gastrointestinal symptoms (e.g. abdominal pain, nausea and flatulence) was similar in tegaserod‐treated and placebo‐treated patients. Pooled analysis of Phase III and post‐US marketing randomized controlled trials did not demonstrate significant differences between tegaserod‐treated and placebo‐treated patients in the incidence of abdominal/pelvic surgery. No episodes of ischaemic colitis were reported in tegaserod‐using patients in any Phase III or post‐marketing randomized controlled trials, and post‐marketing surveillance indicated that the rate of ischaemic colitis in tegaserod‐using patients was lower than that in non‐tegaserod‐using patients. Pooled analysis of Phase III randomized controlled trials demonstrated an increase in the incidence of headaches in tegaserod‐treated (6 mg b.d.) vs. placebo‐treated patients (15% vs. 12.3%, respectively; P < 0.05), although post‐US marketing randomized controlled trials did not demonstrate this increase. Other extra‐gastrointestinal adverse events occurred with similar frequency in tegaserod‐treated and placebo‐treated patients. Tegaserod‐treated patients in randomized controlled trials did not demonstrate significant prolongation of the QT c interval or cardiac arrhythmias compared with placebo‐treated patients. In summary, tegaserod exhibits a favourable safety and tolerability profile in irritable bowel syndrome patients based on data from clinical trials.