Drug Interaction Report

GENERALLY AVOID: Coadministration with inhibitors of the hepatic uptake transporters organic anion transporting polypeptides (OATP) 1B1 and/or OATP 1B3 may increase the plasma concentrations of resmetirom, which has been shown to be a substrate and inhibitor of these transporters in vitro. This may increase the risk and/or severity of resmetirom-related adverse effects (e.g., hepatotoxicity, gallbladder-related adverse reactions, diarrhea, nausea, pruritus, vomiting, constipation, abdominal pain, dizziness); however, clinical data are not available.

MANAGEMENT: According to the manufacturer of resmetirom, concomitant use with inhibitors of OATP 1B1 and/or OATP 1B3 should generally be avoided.

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.