Eluxadoline: a promising therapy that raises many questions

In the United States (US) there are three medications currently approved for the treatment of irritable bowel syndrome (IBS)-D. The most recent additions, rifaximin and eluxadoline, were approved by the US Food and Drug Administration (FDA) on the same day in May, 2015, and were the first therapies approved by the FDA since the approval of alosetron in 2000. Rifaximin, approved for more than a decade for traveler’s diarrhea and since 2010 for the prevention of recurrent hepatic encephalopathy, is well recognized by clinicians and has been used extensively as an off-label treatment for IBS and bloating, as well as for small intestinal bacterial overgrowth. Eluxadoline, however, represents a unique addition to the IBS-D therapeutic milieu and clinicians are just gaining experience with it since it became available in January of 2016. Eluxadoline is an orally administered, minimally absorbed mixed opioid receptor modulator, acting as a mu (µOR) and kappa opioid receptor agonist and delta opioid receptor (δOR) antagonist (1). It is thought that the µOR agonist component of eluxadoline reduces propulsive gastrointestinal motility and chloride secretion while the δOR antagonist component reduces both abdominal pain and opposes µOR activation, tending to ‘normalize’ bowel function rather than constipate (2). The significance of the kappa OR agonism of eluxadoline remains unknown.