The Vibrant orally administered vibrating capsule (Vibrant Gastro), an FDA-cleared medical device, is now available by prescription for treatment of adults with chronic idiopathic constipation (CIC) who have not experienced relief of their bowel symptoms by using laxative therapies at the recommended dosage for at least one month. It is the first drug-free treatment to be authorized by the FDA for this indication.

View the Table: Safety of Drugs for IBS in Pregnancy and Lactation

The FDA has approved the 5-HT4 receptor agonist prucalopride (Motegrity – Shire) for treatment of chronic idiopathic constipation (CIC) in adults. Prucalopride is the only drug currently approved in the US for treatment of CIC that stimulates colonic peristalsis. It has been available in Europe and Canada for several years.

View the Expanded Table: Some Drugs for Chronic Idiopathic Constipation

Tegaserod maleate (Zelnorm), a 5-HT₄ receptor partial agonist that increases gastrointestinal (GI) motility, was approved by the FDA in 2002 for short-term treatment of irritable bowel syndrome with constipation (IBS-C) in women and in 2004 for treatment of chronic idiopathic constipation (CIC) in adults <65 years old.

In 2007, the manufacturer (Novartis) complied with an FDA request to stop marketing the drug based on an unpublished retrospective analysis of clinical trials in IBS-C and other GI motility disorders that showed a higher rate of ischemic cardiovascular events (including cardiovascular death, nonfatal myocardial infarction [MI], and nonfatal stroke) in patients who took tegaserod than in those who took 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 (0.01%) of more than 7000 patients who received placebo.1

The mechanism by which tegaserod could cause cardiovascular ischemia is unknown; 5-HT₁ receptor agonists used to treat migraine, such as sumatriptan (Imitrex, and others), can constrict coronary arteries, and tegaserod has some affinity for 5-HT₁ receptors.1

Based on a re-examination of the data that led to withdrawal of tegaserod and the continued need for a drug with this mechanism of action to treat IBS-C, an FDA advisory committee recommended approval of a supplemental new drug application from a new sponsor (Sloan). The drug is now approved only for treatment of IBS-C in women <65 years old and is contraindicated in patients with a history of MI, stroke, transient ischemic attack, or angina.

Prucalopride (Motegrity), a selective 5-HT₄ receptor agonist recently approved by the FDA for treatment of CIC, will be reviewed in a future issue. It has less affinity for 5-HT₁ receptors than tegaserod.2

1. In brief: tegaserod withdrawn. Med Lett Drugs Ther 2007; 49:40.
2. J Tack et al. Systematic review: cardiovascular safety profile of 5-HT₄ agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther 2012; 35:745.

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