Drug Interaction Report

ADJUST DOSE: Coadministration with inhibitors of organic anion transporting polypeptide (OATP) 1B1 may significantly increase the plasma concentrations of eluxadoline. Based on available data, inhibition of OATP1B1-mediated hepatic uptake appears to reduce both the hepatic first-pass extraction and systemic biliary clearance of eluxadoline. In 30 healthy volunteers, administration of a single 100 mg dose of eluxadoline with a single 600 mg dose of cyclosporine, a known OATP1B1 inhibitor, increased eluxadoline peak plasma concentration (Cmax) and systemic exposure (AUC) by 6.2- and 4.4-fold, respectively, compared to administration of eluxadoline alone. Adverse events were reported in 6 study subjects during coadministration of eluxadoline with cyclosporine and in 2 subjects during administration of eluxadoline alone.

MANAGEMENT: The recommended dosage of eluxadoline is 75 mg twice daily when used with OATP1B1 inhibitors. Patients should be monitored for adverse effects such as sedation, nausea, vomiting, constipation, abdominal pain, liver enzyme elevations, and pancreatitis.

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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.

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ADJUST DOSING INTERVAL: Food does not appear to substantially alter the pharmacokinetics of tipranavir. When tipranavir capsules or oral solution was coadministered with ritonavir capsules at steady-state, no clinically significant changes in tipranavir peak plasma concentration (Cmax) and systemic exposure (AUC) were observed under fed conditions (500 to 682 kcal, 23% to 25% calories from fat) relative to fasted conditions. The effect of food on tipranavir exposure during coadministration with ritonavir tablets has not been evaluated. High-fat foods may enhance the gastrointestinal absorption of tipranavir. In a multiple-dose study, administration of tipranavir capsules with a high-fat meal (868 kcal, 53% from fat, 31% from carbohydrates) increased the oral bioavailability of tipranavir by 31% compared to administration with toast and skimmed milk, but did not significantly affect tipranavir Cmax. Thus, tipranavir may be safely taken with standard or high-fat meals.

MANAGEMENT: Tipranavir coadministered with low-dose ritonavir should be taken with food to improve the gastrointestinal tolerability of ritonavir. According to the product labeling, tipranavir coadministered with ritonavir capsules or solution can be taken with or without meals, whereas tipranavir coadministered with ritonavir tablets must be taken with meals.

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