Rifaximin and eluxadoline - newly approved treatments for diarrhea-predominant irritable bowel syndrome: what is their role in clinical practice alongside alosetron?

Expert Opin Pharmacother. 2016;17(3):311-22. doi: 10.1517/14656566.2016.1118052. Epub 2015 Dec 8.


Introduction: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal condition in which patients experience abdominal pain, diarrhea, bloating, cramps, flatulence, fecal urgency, and incontinence.

Areas covered: We review two recently approved therapies that focus on treating underlying pathogenic mechanisms of IBS-D: (1) the non-absorbable antibiotic rifaximin, and (2) the opioid receptor agonist/antagonist eluxadoline. We compare the safety and efficacy data emerging from rifaximin and eluxadoline registration trials with safety and efficacy data from the alosetron clinical development program.

Expert opinion: The rifaximin and eluxadoline clinical development programs for IBS-D have demonstrated significant improvement in IBS-D endpoints compared to placebo. Direct comparison of primary endpoint results from the alosetron, rifaximin, and eluxadoline pivotal trials is not possible; however, general estimates of efficacy can be made, and these demonstrate similar and significantly greater responses to 'adequate relief' and a composite endpoint of abdominal pain/stool form for each agent compared to placebo. With the recent approval in the United States of rifaximin and eluxadoline for IBS-D, how should clinicians employ these agents? We suggest that they be utilized sequentially, taking into consideration patient symptoms and severity, prior medical history, mode of action, cost, availability, managed care coverage, and adverse event profiles.

Keywords: 5-HT3 receptor antagonist; adequate relief; alosetron; composite endpoint of abdominal pain and stool consistency; delta opioid receptor (δOR) antagonist; diarrhea-predominant irritable bowel syndrome; eluxadoline; mu opioid receptor (μOR) agonist; non-absorbable antibiotic; rifaximin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abdominal Pain / drug therapy
  • Abdominal Pain / physiopathology
  • Anti-Bacterial Agents / therapeutic use
  • Carbolines / therapeutic use*
  • Diarrhea / drug therapy*
  • Diarrhea / physiopathology
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Imidazoles / therapeutic use*
  • Irritable Bowel Syndrome / drug therapy*
  • Irritable Bowel Syndrome / physiopathology
  • Narcotic Antagonists / therapeutic use
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / therapeutic use
  • Receptors, Opioid / agonists
  • Rifamycins / therapeutic use*
  • Rifaximin
  • Serotonin 5-HT3 Receptor Antagonists / therapeutic use


  • Anti-Bacterial Agents
  • Carbolines
  • Gastrointestinal Agents
  • Imidazoles
  • Narcotic Antagonists
  • Receptors, Opioid
  • Rifamycins
  • Serotonin 5-HT3 Receptor Antagonists
  • alosetron
  • eluxadoline
  • Phenylalanine
  • Rifaximin