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Update on the Management of Diarrhea-Predominant Irritable Bowel Syndrome: Focus on Rifaximin and Eluxadoline.
Pharmacotherapy 2016; 36(3):300-16P

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+Show Affiliations

Fairleigh Dickinson University School of Pharmacy, Florham Park, New Jersey.Division of Gastroenterology, Saint Clare's Hospital Dover/General, Dover, New Jersey.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

26971716

Citation

Rivkin, Anastasia, and Sergey Rybalov. "Update On the Management of Diarrhea-Predominant Irritable Bowel Syndrome: Focus On Rifaximin and Eluxadoline." Pharmacotherapy, vol. 36, no. 3, 2016, pp. 300-16.
Rivkin A, Rybalov S. Update on the Management of Diarrhea-Predominant Irritable Bowel Syndrome: Focus on Rifaximin and Eluxadoline. Pharmacotherapy. 2016;36(3):300-16.
Rivkin, A., & Rybalov, S. (2016). Update on the Management of Diarrhea-Predominant Irritable Bowel Syndrome: Focus on Rifaximin and Eluxadoline. Pharmacotherapy, 36(3), pp. 300-16. doi:10.1002/phar.1712.
Rivkin A, Rybalov S. Update On the Management of Diarrhea-Predominant Irritable Bowel Syndrome: Focus On Rifaximin and Eluxadoline. Pharmacotherapy. 2016;36(3):300-16. PubMed PMID: 26971716.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Update on the Management of Diarrhea-Predominant Irritable Bowel Syndrome: Focus on Rifaximin and Eluxadoline. AU - Rivkin,Anastasia, AU - Rybalov,Sergey, Y1 - 2016/03/11/ PY - 2016/3/15/entrez PY - 2016/3/15/pubmed PY - 2016/12/17/medline KW - diarrhea KW - eluxadoline KW - irritable bowel syndrome KW - rifaximin SP - 300 EP - 16 JF - Pharmacotherapy JO - Pharmacotherapy VL - 36 IS - 3 N2 - 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. SN - 1875-9114 UR - https://www.unboundmedicine.com/medline/citation/26971716/Update_on_the_Management_of_Diarrhea_Predominant_Irritable_Bowel_Syndrome:_Focus_on_Rifaximin_and_Eluxadoline_ L2 - https://doi.org/10.1002/phar.1712 DB - PRIME DP - Unbound Medicine ER -