Ondansetron for Irritable Bowel Syndrome

Article

A recent trial indicates that the antinausea medication ondansetron may have some utility in treating the symptoms of diarrhea-associated irritable bowel syndrome.

A recent trial indicates that the antinausea medication ondansetron may have some utility in treating the symptoms of diarrhea-associated irritable bowel syndrome.

Investigators at the University of Nottingham and associated hospitals in the United Kingdom found that ondansetron improved stool consistency and several markers of diarrhea-associated irritable bowel syndrome (IBS-D) symptoms compared with placebo.

In the trial, all patients had IBS-D as defined by the Rome III criteria. After a 2- to 3-week washout period in which patients did not take medication for IBS, investigators randomized 120 patients to each treatment group in an approximately 1:1 ratio. Patients then received 5 weeks of treatment with ondansetron or placebo and recorded bowel symptoms in a diary. Over the first 3 weeks, patients were instructed to increase the dose slowly to a maximum total daily dose of 24 mg (8 mg 3 times daily). Despite these instructions, the median dose of ondansetron used in the trial was 4 mg daily.

Regular use of ondansetron reduced defecation frequency, self-reported bowel urgency, and self-reported symptoms of bloating. Almost two-thirds of patients (65%) treated with ondansetron reported adequate relief of IBS symptoms compared with 14% of patients receiving placebo. Although investigators speculated that abdominal pain measures might improve with higher dosages of ondansetron, no significant improvement in self-reported abdominal pain scores was observed in the trial.

Ondansetron works by blocking a subtype of serotonin receptors associated with nausea (5-HT3). Blocking this serotonin receptor may also reduce the serotonergic signaling that induces symptoms of loose stool and bowel urgency in patients with IBS.

Although slowing colonic transit time may be therapeutic at low doses, large doses of ondansetron may lead to constipation. This adverse event occurred in 9% of patients taking ondansetron. Constipation was generally reversible with a dose reduction, although 2% of patients stopped taking ondansetron due to the adverse event.

It is important to note that, unlike the 5-HT3 antagonist Lotronex (alosetron), ondansetron does not have an FDA-approved indication for IBS. Alosetron was temporarily withdrawn, but later placed back on the market in 2002. In the United Kingdom, alosetron was withdrawn due to rare cases of ischemic colitis that occurred with a frequency of approximately 0.7 cases per 100,000 patient-years. In the United States, alosetron is still available, but the medication carries a black box warning for ischemic colitis, is distributed with a Risk Evaluation and Mitigation Strategy (REMS), and can only be used in women. The study by Garsed et al showed a benefit of ondansetron in a population of both men and women.

This small study is inadequate to prove the safety of ondansetron in patients with IBS, but researchers noted that, unlike alosetron, ondansetron has been used for over 25 years without a single report of ischemic colitis. Off-label use of ondansetron may offer some patients with IBS-D a lower-cost option with evidence of efficacy in symptom reduction at doses as low as 4 mg daily.

Related Videos
Image Credit: SciePro - stock.adobe.com
Pharmacist selling medications in the pharmacy | Image Credit: rh2010 - stock.adobe.com
Atopic dermatitis on a patient's hand -- Image credit: Ольга Тернавская | stock.adobe.com
biosimilar word or concept represented by wooden letter tiles on a wooden table with glasses and a book | Image Credit: lexiconimages - stock.adobe.com
Image credit: alicja neumiler | stock.adobe.com
Laboratory test tubes and solution with stethoscope background | Image Credit: Shutter2U - stock.adobe.com
Laboratory test tubes and solution with stethoscope background | Image Credit: Shutter2U - stock.adobe.com
Image credit: Krakenimages.com | stock.adobe.com
Human brain digital illustration. Electrical activity, flashes, and lightning on a blue background. | Image Credit: Siarhei - stock.adobe.com
© 2024 MJH Life Sciences

All rights reserved.