PMID- 29090081 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240327 IS - 2040-6223 (Print) IS - 2040-6231 (Electronic) IS - 2040-6223 (Linking) VI - 8 IP - 11 DP - 2017 Nov TI - Eluxadoline in irritable bowel syndrome with diarrhea: rationale, evidence and place in therapy. PG - 153-160 LID - 10.1177/2040622317714389 [doi] AB - Irritable bowel syndrome (IBS) is the most common gastrointestinal (GI) disorder worldwide, however treatment options for diarrhea-predominant IBS (IBS-D) remain limited. Eluxadoline, a micro- and kappa-opioid receptor agonist and delta-opioid receptor antagonist, was recently approved for the treatment of IBS-D. A novel compound first described in 2008, eluxadoline was shown to normalize GI transit, with a subsequent phase I demonstrating its safety and tolerability in healthy adults. In 2016, two randomized, double-blind, placebo-controlled phase III trials studying eluxadoline use at 75 mg and 100 mg twice daily over 26 weeks demonstrated a significant improvement in stool consistency and many global symptoms of IBS. However, the data did not demonstrate a significant advantage over placebo using the United States Food and Drug Administration (US FDA) and European Medicines Agency (EMA) endpoints for abdominal pain. Safety and tolerability data, pooled from both phase II and III studies, suggest that eluxadoline is generally well tolerated with the most common adverse events (AEs) occurring in approximately 3-8% of patients and included nausea, constipation, and abdominal pain. The most common serious adverse event (SAE) is pancreatitis, which had a 0.4% incidence. Recent US FDA reports reporting severe pancreatitis and sphincter of Oddi dysfunction after short-term use of eluxadoline in patients without a gallbladder has added a history of cholecystectomy as an important contraindication. Eluxadoline is also contraindicated in patients with a history of biliary duct obstruction, sphincter of Oddi dysfunction, active alcohol abuse, history of pancreatitis or known pancreatic duct obstruction, severe hepatic impairment, severe or chronic constipation, or known mechanical gastrointestinal obstruction. As a new drug to enter the IBS-D market, the place of eluxadoline in the hierarchy of IBS treatments is still to be determined. In this article, we review the development and clinical trial data behind the approval of eluxadoline with a focus on safety data and its use in clinical practice. FAU - Barshop, Kenneth AU - Barshop K AD - Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA. FAU - Staller, Kyle AU - Staller K AD - Division of Gastroenterology, Center for Neurointestinal Health, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. LA - eng PT - Journal Article PT - Review DEP - 20170621 PL - United States TA - Ther Adv Chronic Dis JT - Therapeutic advances in chronic disease JID - 101532140 PMC - PMC5638229 OTO - NOTNLM OT - abdominal pain OT - diarrhea OT - eluxadoline OT - functional GI disease OT - irritable bowel syndrome OT - pancreatitis COIS- Conflict of interest statement: The authors declare that there is no conflict of interest. EDAT- 2017/11/02 06:00 MHDA- 2017/11/02 06:01 PMCR- 2017/11/01 CRDT- 2017/11/02 06:00 PHST- 2017/01/19 00:00 [received] PHST- 2017/05/17 00:00 [accepted] PHST- 2017/11/02 06:00 [entrez] PHST- 2017/11/02 06:00 [pubmed] PHST- 2017/11/02 06:01 [medline] PHST- 2017/11/01 00:00 [pmc-release] AID - 10.1177_2040622317714389 [pii] AID - 10.1177/2040622317714389 [doi] PST - ppublish SO - Ther Adv Chronic Dis. 2017 Nov;8(11):153-160. doi: 10.1177/2040622317714389. Epub 2017 Jun 21.