Eluxadoline Efficacy in IBS-D Patients Who Report Prior Loperamide Use

Am J Gastroenterol. 2017 Jun;112(6):924-932. doi: 10.1038/ajg.2017.72. Epub 2017 Apr 18.


Objectives: Irritable bowel syndrome with diarrhea (IBS-D) is often managed with over-the-counter therapies such as loperamide, though with limited success. This analysis evaluated the efficacy of eluxadoline in patients previously treated with loperamide in two phase 3 studies.

Methods: Adults with IBS-D (Rome III criteria) were enrolled and randomized to placebo or eluxadoline (75 or 100 mg) twice daily for 26 (IBS-3002) or 52 (IBS-3001) weeks. Patients reported loperamide use over the previous year and recorded their rescue loperamide use during the studies. The primary efficacy end point was the proportion of patients with a composite response of simultaneous improvement in abdominal pain and reduction in diarrhea.

Results: A total of 2,428 patients were enrolled; 36.0% reported prior loperamide use, of whom 61.8% reported prior inadequate IBS-D symptom control with loperamide. Among patients with prior loperamide use, a greater proportion treated with eluxadoline (75 and 100 mg) were composite responders vs. those treated with placebo with inadequate prior symptom control, over weeks 1-12 (26.3% (P=0.001) and 27.0% (P<0.001) vs. 12.7%, respectively); similar results were observed over weeks 1-26. When daily rescue loperamide use was imputed as a nonresponse day, the composite responder rate was still higher in patients receiving eluxadoline (75 and 100 mg) vs. placebo over weeks 1-12 (P<0.001) and weeks 1-26 (P<0.001). Adverse events included nausea and abdominal pain.

Conclusions: Eluxadoline effectively and safely treats IBS-D symptoms of abdominal pain and diarrhea in patients who self-report either adequate or inadequate control of their symptoms with prior loperamide treatment, with comparable efficacy and safety irrespective of the use of loperamide as a rescue medication during eluxadoline treatment.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Abdominal Pain / etiology
  • Adult
  • Antidiarrheals / adverse effects
  • Antidiarrheals / therapeutic use*
  • Diarrhea / etiology
  • Double-Blind Method
  • Female
  • Gastrointestinal Agents / adverse effects
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Imidazoles / adverse effects
  • Imidazoles / therapeutic use*
  • Irritable Bowel Syndrome / complications
  • Irritable Bowel Syndrome / drug therapy*
  • Loperamide / adverse effects
  • Loperamide / therapeutic use*
  • Male
  • Middle Aged
  • Pain Measurement
  • Phenylalanine / adverse effects
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / therapeutic use
  • Symptom Assessment


  • Antidiarrheals
  • Gastrointestinal Agents
  • Imidazoles
  • eluxadoline
  • Phenylalanine
  • Loperamide