Eluxadoline

• Irritable Bowel Syndrome with Diarrhea (IBS-D)
• IBS-D Abdominal Pain
• Chronic Diarrhea from IBS
• Functional GI Disorders

Eluxadoline is a mixed opioid receptor agonist/antagonist used for the treatment of irritable bowel syndrome with diarrhea (IBS-D). This medication acts locally in the gastrointestinal tract to reduce abdominal pain and improve stool consistency without causing systemic opioid effects.

Mechanism of Action

Eluxadoline has a unique mixed opioid receptor mechanism: it is a mu-opioid receptor agonist, delta-opioid receptor antagonist, and kappa-opioid receptor agonist. In the gastrointestinal tract, mu-opioid agonism reduces bowel motility and decreases visceral hypersensitivity, while delta-opioid antagonism may counteract constipating effects and enhance analgesia. The kappa agonism may contribute to visceral analgesia. This combination reduces diarrhea and abdominal pain associated with IBS-D. Eluxadoline has minimal systemic absorption due to extensive first-pass metabolism and P-glycoprotein-mediated efflux, limiting CNS effects.

Available Formulations

Eluxadoline is available as oral tablets in 75 mg and 100 mg strengths. The tablets should be taken with food to reduce the risk of spasm of the sphincter of Oddi. Eluxadoline is a Schedule IV controlled substance due to its opioid receptor activity, though abuse potential is low due to minimal systemic exposure.

Medical Uses

Eluxadoline is FDA-approved for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults. Clinical trials demonstrated improvement in both abdominal pain and stool consistency compared to placebo, with patients reporting improvement as early as the first week of treatment. The medication is indicated for patients who have had inadequate response to conventional therapies including dietary modification and anti-diarrheals.

Dosing Guidelines

The recommended dose is 100 mg taken orally twice daily with food. A dose of 75 mg twice daily is recommended for patients who: do not have a gallbladder, are unable to tolerate the 100 mg dose, are receiving concomitant OATP1B1 inhibitors (e.g., cyclosporine, gemfibrozil, antiretrovirals), or have mild to moderate hepatic impairment. The medication should not be taken without food due to increased risk of sphincter of Oddi spasm.

Important Safety Information

Eluxadoline is contraindicated in patients without a gallbladder due to increased risk of sphincter of Oddi spasm, patients with known or suspected biliary duct obstruction or sphincter of Oddi disease/dysfunction, alcoholism or heavy alcohol use (more than 3 drinks/day), history of pancreatitis or structural pancreatic disease, severe hepatic impairment, or severe constipation. Sphincter of Oddi spasm and pancreatitis have occurred, typically within the first week of treatment. Patients should be advised to discontinue and seek medical attention if they experience severe abdominal pain.

Drug Interactions

Strong OATP1B1 inhibitors (cyclosporine, gemfibrozil) increase eluxadoline exposure; use the 75 mg dose. Drugs that cause constipation (anticholinergics, opioids, loperamide) may increase risk of serious constipation-related adverse events. Eluxadoline may increase rosuvastatin levels; avoid concomitant use. Strong CYP inhibitors may increase eluxadoline exposure. Concurrent use with medications that affect the sphincter of Oddi should be avoided.

Special Populations

There are no adequate studies in pregnant women; animal studies showed no adverse effects. Eluxadoline is minimally absorbed; breastfeeding is likely compatible but use caution. Safety and efficacy have not been established in pediatric patients. Clinical trials included patients up to 80 years; no overall differences in safety or efficacy were observed in elderly patients. Patients with mild to moderate hepatic impairment should use the 75 mg dose; contraindicated in severe impairment. No dose adjustment is needed for renal impairment, but use with caution in severe impairment due to limited data.