Drug Interaction Report

GENERALLY AVOID: Coadministration of revefenacin with inhibitors of organic anion transporting polypeptide (OATP) 1B1 and/or 1B3 may increase systemic exposure to its active metabolite, which has been reported to be a substrate of the hepatic uptake transporters. No pharmacokinetic data are available, but increased anticholinergic adverse effects such as mydriasis, blurred vision, heat intolerance, fever, dry mouth, tachycardia, urinary retention, constipation, and glaucoma (onset or exacerbation) may occur. In study patients, revefenacin was rapidly converted to its active metabolite following inhaled administration, and plasma exposures of the metabolite exceeded those of revefenacin by approximately 4- to 6-fold. The activity of the metabolite at target muscarinic receptors is approximately one-third to one-tenth that of revefenacin and could potentially contribute to systemic antimuscarinic effects at therapeutic doses.

MANAGEMENT: Concomitant use of revefenacin with OATP 1B1 and/or 1B3 inhibitors is not recommended.

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.