Alosetron, Ramosetron Best Medications for IBS With Diarrhea or Mixed Stool Pattern

By Will Boggs MD

May 01, 2019

NEW YORK (Reuters Health) - Alosetron and ramosetron appear to be the best medications for treating irritable bowel syndrome (IBS) with diarrhea (IBS-D) or mixed stool pattern (IBS-M), according to a network meta-analysis.

"Available treatments for IBS-D performed only modestly, and the two that are more easily available were ranked relatively low down for most endpoints," Dr. Alexander C. Ford from Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK told Reuters Health.

Alosetron and ramosetron are 5-hydroxytryptamine-3 (5-HT3) antagonists that seem to slow gastrointestinal transit, alter rectal compliance, and reduce visceral sensitivity.

Rifamixin and eluxadoline have also been used to treat IBS-D and IBS-M. Rifamixin is a minimally absorbed broad-spectrum antibiotic that likely beneficially alters gastrointestinal microbiota. Eluxadoline is a peripherally acting opioid receptor agonist with minimal oral bioavailability that reduces visceral hypersensitivity and slows gastrointestinal transit.

Dr. Ford's team conducted a network meta-analysis to allow comparisons between all of these drugs, compared with each other or with placebo.

Based on data from 10 randomized controlled trials, all treatments were significantly more effective than placebo, and alosetron 1 mg twice daily ranked most effective when efficacy was based on failure to achieve the FDA-recommended endpoint to define treatment response.

When all treatments, including placebo, were compared with each other, the probability of alosetron being the most effective was 97%, according to the April 17th online report in Gut.

Alosetron also ranked first for the endpoints of global IBS symptom response and stool consistency response, whereas ramosetron 2.5 mcg once daily ranked first for the endpoint of abdominal pain response.

In terms of overall adverse events, rifamixin 550 mg three times daily ranked best and ramosetron 2.5 mcg ranked worst, with all drugs having significantly higher trial dropout rates due to adverse events, compared with placebo.

"I believe we should be trying to improve access to 5-HT3 antagonists for patients with IBS with diarrhea," Dr. Ford said. "In the UK, we are conducting a large randomized trial of ondansetron, another 5-HT3 antagonist with a well-established safety profile, in patients with IBS with diarrhea."


Gut 2019.