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Update on the Management of Diarrhea‐Predominant Irritable Bowel Syndrome: Focus on Rifaximin and Eluxadoline
Author(s) -
Rivkin Anastasia,
Rybalov Sergey
Publication year - 2016
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.1712
Subject(s) - rifaximin , irritable bowel syndrome , medicine , placebo , gastroenterology , abdominal pain , clinical endpoint , diarrhea , constipation , randomized controlled trial , antibiotics , pathology , alternative medicine , microbiology and biotechnology , biology
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.