Drug Interaction Report

GENERALLY AVOID: Coadministration with rolapitant may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter. When a 0.5 mg dose of digoxin, a P-gp probe substrate, was administered with a 180 mg dose of rolapitant, digoxin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 70% and 30%, respectively.

MANAGEMENT: Concomitant use of rolapitant with drugs that are P-gp substrates should generally be avoided. If concomitant administration is unavoidable, caution is advised, particularly with drugs that have a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever rolapitant is added to or withdrawn from therapy.

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.