Luminary Learning Gastrointestinal Disorder- Issue 1

20  • LUMINARY LEARNING: GASTROINTESTINAL DISORDERS Eluxadoline Eluxadoline is a peripherally-restricted mixed MOR agonist and DOR antagonist approved by FDA in May 2015 [34, 38]. In 2013 a phase II clinical trial (n = 807) demonstrated the effective- ness of eluxadoline versus placebo against global IBS-D symptoms [39]. Patients receiving a drug were significantly more likely to meet the U.S. FDA response end point during the full 12 weeks of the study than those receiving placebo. Eluxadoline was well tolerated with a low incidence of constipation. Phase III trials (n = 2428 patients in total) confirmed these results and showed that treatment with eluxadoline (75 or 100 mg twice daily) lead to simultaneous improvement in abdominal pain and stool consistency on the same day for ≥50 % of days over weeks 1–12 and 1–26 of the study (for more details please see Nee et al. [34]). On the other hand a nonsignificant improvement in worst abdominal pain scores in those who received eluxadoline compared to placebo was observed. Common adverse effects in the two phase III clinical trials were nausea, headache, nasopharyngitis, abdominal pain and constipation but rates of discontinuation due to constipation were low (approx. 1.5 %) for both eluxadoline and placebo [40]. Known contrain- dications to the treatment with eluxadoline include: (i) biliary duct obstruction, or sphincter of Oddi disease or dysfunction, (ii) alcohol abuse or addiction, or patients who drink more than three alcoholic beverages per day, (iii) a history of pancreatitis or structural diseases of the pancre- as, including known or suspected pancreatic duct obstruction, (iv) a history of chronic or severe constipation or known or suspected mechanical gastrointestinal obstruction. Rifaximin Rifaximin is another drug for IBS-D approved by FDA in 2015. It is a nonabsorbable, semisyn- thetic antibiotic belonging to the rifamycin family. The use of antibiotics for the treatment of IBS emerged from the observation that gut microflora differs between IBS and general population. Furthermore epidemiological data reveal that up to 31 % of IBS cases are caused by an episode of gastroenteritis [34]. Rifaximin targets the β-subunit of bacterial RNA polymerase which is responsible for the transcription process [41]. It does not affect the overall composition of the microbiota but appear to influence mainly potentially detrimental species such as Clostridium sp. and increases the presence of some species, such as Faecalibacterium prausnitzii [42]. Clinical trials suggest that the drug can reduce global IBS symptoms, improve bloating, abdominal pain, and stool consistency in patients with non-constipated IBS [43]. While other anti- IBS therapies require daily administration to maintain their efficacy, 2-week rifaximin treatment can achieve symptom improvement that persists up to 12 weeks post-treatment [44]. However, in the clinical trial it has been shown that 64 % of patients who underwent a 2-week therapy with rifaximin (550 mg) develop a relapse in the 18 weeks follow up hence FDA recommends a 14-day therapy with rifaximin at the dose of 550 mg (orally), three times a day. In case of the recurrence of the symptoms therapy may be repeated for another 14 days. Rifaximin is well-tolerated both after single and repeated treatments with a side effect profile comparable to that of placebo. The most common adverse events caused by rifaximin are headache, upper respiratory infection, nausea, nasopharyngitis, diarrhea and abdominal pain.