Drug Interaction Report

GENERALLY AVOID: The risk of constipation and serious constipation-related adverse reactions may be increased when eluxadoline is used with other drugs that are also associated with this adverse effect. In placebo-controlled studies, constipation occurred in 7% and 8% of patients receiving eluxadoline 75 mg twice daily and 100 mg twice daily, respectively. Approximately 50% of constipation events occurred within the first 2 weeks of treatment, while the majority occurred within the first 3 months. The rates of constipation were similar between eluxadoline and placebo beyond the first 3 months of therapy.

MANAGEMENT: Concomitant use of eluxadoline with other drugs that can cause constipation such as alosetron, anticholinergics, and opioids should generally be avoided. Loperamide may be used occasionally for acute management of severe diarrhea, but chronic use is not recommended, and it should be discontinued immediately if constipation occurs. Eluxadoline should also be discontinued if constipation occurs for more than 4 days.

CONTRAINDICATED: Consumption of more than 3 alcoholic beverages per day may increase the risk of acute pancreatitis during treatment with eluxadoline. Pancreatitis has been reported rarely during clinical trials of eluxadoline, and may or may not be related to sphincter of Oddi spasm.

ADJUST DOSING INTERVAL: High-fat meals may reduce the oral bioavailability of eluxadoline. In 28 healthy volunteers, administration of a single 100 mg dose of eluxadoline with a high-fat meal (approximately 800 to 1000 total calories, 50% from fat) decreased eluxadoline peak plasma concentration (Cmax) and systemic exposure (AUC) by 50% and 60%, respectively, compared to administration in the fasted state. There was no significant effect on the time to peak concentration (Tmax). The clinical relevance of this interaction is unknown. It should be noted that phase 3 clinical trials were conducted under fed conditions.

MANAGEMENT: Chronic or acute excessive use of alcohol should be avoided during treatment with eluxadoline. Alcoholism, alcohol abuse, alcohol addiction, and consumption of more than 3 alcoholic beverages per day are considered contraindications to the use of eluxadoline. The product labeling recommends taking eluxadoline with food. Patients should be advised to stop taking eluxadoline and seek medical attention if they experience potential symptoms of pancreatitis such as persistent nausea, vomiting, abdominal tenderness, and upper abdominal pain, especially that which is made worse after eating or radiates to the back or shoulders.