Tegaserod maleate (Zelnorm – Novartis), a partial serotonin 5-HT4 receptor agonist that increases gastrointestinal motility, was approved by the FDA in 2002 for short-term treatment of constipation-predominant irritable bowel syndrome in women,1 and in 2004 for treatment of chronic constipation in adults ≤65 years old. Its efficacy has not been impressive statistically, but according to Medical Letter consultants some patients with slow-transit constipation have benefited from taking the drug. Diarrhea has been its main adverse effect.2
The FDA now has requested that the manufacturer stop marketing the drug based on an unpublished postmarketing analysis of earlier clinical trials that showed a higher rate of serious cardiovascular events (including angina, myocardial infarction and stroke) in patients who took tegaserod compared to placebo. Among more than 11,600 patients treated with tegaserod for 1-3 months, 13 (0.11%) had a confirmed ischemic event compared to only 1 patient (0.01%) among more than 7000 treated with placebo. The mechanism by which tegaserod would cause cardiovascular ischemia is unknown; serotonin 5-HT1 receptor agonists used to treat migraine, such as sumatriptan (Imitrex), can constrict coronary arteries, and tegaserod has some affinity for 5-HT1 receptors.3
Tegaserod may still be available, possibly through a special access program, for patients who do not have other treatment options.