title: Update on the Management of Diarrhea-Predominant Irritable Bowel Syndrome: Focus on Rifaximin and Eluxadoline.
abstract: Diarrhea-predominant irritable bowel syndrome (IBS-D) is one of the most common diagnoses made by gastroenterologists. Current pharmacologic treatments for IBS-D include fiber supplements, antidiarrheal over-the-counter medications, probiotics, antispasmodics, antidepressants, and a 5-hydroxytryptophan 3 receptor antagonist. All of these options have limited efficacy in managing IBS-D. Rifaximin, a nonabsorbable antibiotic, has been evaluated in patients with IBS-D. In two randomized, double-blind, placebo-controlled phase III trials evaluating rifaximin 550 mg by mouth 3 times/day for 14 days, the primary efficacy end point was achieved by 9% more patients randomized to the rifaximin group compared with placebo (40.7% vs 31.7%, p<0.001, number needed to treat ~11). The primary efficacy end point was defined as the proportion of patients having adequate relief of global IBS symptoms for at least 2 of the 4 weeks during the primary follow-up period (weeks 3-6). In the phase III trial examining the efficacy and safety of repeated courses of rifaximin in patients who responded to the initial 2-week course, rifaximin given for up to two additional courses provided a statistically significant incremental benefit (33% vs 25%, p=0.02). Eluxadoline is a gut-targeting μ and κ opioid receptor agonist and a δ opioid receptor antagonist. The dual mechanism of eluxadoline may explain the antidiarrheal and abdominal pain-modulating properties and lack of profound constipation. In two identically designed randomized, double-blind, placebo-controlled phase III studies, 10.3% more patients in an eluxadoline 100 mg by mouth twice/day group met the primary efficacy end point during the follow-up 1-12 week period compared with placebo (p<0.001). The primary efficacy end point was a composite response, defined as improvement in worst abdominal pain and stool consistency at the same time on most (50% or more) days during the follow-up period. This review evaluates evidence for the use of rifaximin and eluxadoline in patients with IBS-D. Rifaximin provides an additional modality for the management of IBS-D patients; it has mild to moderate efficacy similar to other currently available treatment options. Rifaximin is relatively safe, lacks significant drug-drug interactions, and can be used for up to two additional retreatment courses. This may make rifaximin a possible initial or second-line treatment option. Eluxadoline can also offer relief to patients with IBS-D. While effective, because of several limitations, including drug-drug interactions and drug disease contraindications, as well as current lack of clinical experience, it may be tried as a second- or third-line agent.
authors.affiliation: Fairleigh Dickinson University School of Pharmacy, Florham Park, New Jersey.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Rivkin
authors.affiliation: Division of Gastroenterology, Saint Clare's Hospital Dover/General, Dover, New Jersey.
authors.forename: Sergey
authors.initials: S
authors.lastname: Rybalov
mesh_terms: D000284:Administration, Oral; D003967:Diarrhea / Q000188:drug therapy* / Q000209:etiology; D019468:Disease Management; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy*; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012294:Rifamycins / Q000008:administration & dosage / Q000627:therapeutic use*; D000078262:Rifaximin
chemical_list: D005765:Gastrointestinal Agents; D007093:Imidazoles; D012294:Rifamycins; C583636:eluxadoline; D010649:Phenylalanine; D000078262:Rifaximin
keywords: diarrhea; eluxadoline; irritable bowel syndrome; rifaximin