This article was accepted for publication after full peer-review.
Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: a pooled analysis of randomised, double-blind, placebo-controlled trials
Article first published online: 3 APR 2014
© 2014 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Alimentary Pharmacology & Therapeutics
Volume 39, Issue 10, pages 1161–1168, May 2014
How to Cite
Schoenfeld, P., Pimentel, M., Chang, L., Lembo, A., Chey, W. D., Yu, J., Paterson, C., Bortey, E. and Forbes, W. P. (2014), Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: a pooled analysis of randomised, double-blind, placebo-controlled trials. Alimentary Pharmacology & Therapeutics, 39: 1161–1168. doi: 10.1111/apt.12735
- Issue published online: 16 APR 2014
- Article first published online: 3 APR 2014
- Manuscript Accepted: 15 MAR 2014
- Manuscript Revised: 14 MAR 2014
- Manuscript Revised: 19 OCT 2013
- Manuscript Received: 3 OCT 2013
- Salix Pharmaceuticals, Inc.
The efficacy of rifaximin, a nonsystemic, gut-targeted antibiotic for reducing non–constipation-predominant irritable bowel syndrome (non-C IBS) symptoms, has been demonstrated in one phase 2b and two phase 3 randomised, double-blind, placebo-controlled trials, but detailed data about rifaximin safety and tolerability during treatment and subsequent follow-up periods are lacking.
To assess and determine the frequency of rifaximin and placebo adverse events (AEs) in phase 2b and phase 3 non-C IBS trials.
A post hoc pooled safety analysis of the phase 2b (rifaximin 275, 550, and 1100 mg twice daily for 2 weeks; 550 mg twice daily for 4 weeks) and phase 3 (rifaximin 550 mg three times daily for 2 weeks) studies was performed. Data on treatment and post-treatment AEs were collected. Patients were followed up for 12 weeks and 10 weeks post-treatment in the phase 2b and phase 3 trials, respectively.
Patients receiving rifaximin (n = 1103) and placebo (n = 829) had a similar incidence of drug-related AEs (12.1% vs. 10.7%), serious AEs (1.5% vs. 2.2%), drug-related AEs resulting in study discontinuation (0.8% vs. 0.8%), gastrointestinal-associated AEs (12.2% vs. 12.2%) and infection-associated AEs (8.5% vs. 9.5%). There were no cases of Clostridium difficile colitis or deaths.
The safety and tolerability profile of rifaximin during treatment and post-treatment was comparable to placebo. Future research should define the safety and tolerability profile, including risk of C. difficile colitis and microbial antibiotic resistance, with repeated courses of rifaximin in patients with non—constipation-predominant irritable bowel syndrome (ClinicalTrials.gov: NCT00269412, NCT00731679, and NCT00724126).