Drug Interaction Report

MONITOR: Coadministration with inhibitors of organic anion transporting polypeptides (OATP) 1B1 and/or 1B3 may increase the plasma concentrations and effects of momelotinib, which is a substrate of the hepatic uptake transporters. Clinical studies have demonstrated that concomitant use with a single dose of the OATP1B1/B3 inhibitor rifampin increased the peak plasma concentration (Cmax) and systemic exposure (AUC) of momelotinib by 40% and 57% respectively. The Cmax and AUC of the active metabolite of momelotinib, M21, was also increased, by 6% and 12%, respectively.

MANAGEMENT: Caution is advised if momelotinib is used in combination with inhibitors of OATP1B1 and/or 1B3. Dosage adjustments of momelotinib may be required. Patients should be advised to report any momelotinib-related adverse reactions such as bacterial or viral infection, thrombocytopenia, neutropenia, hepatotoxicity, thrombosis, and adverse cardiovascular events.

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.