Drug Interaction Report

MONITOR: Coadministration with inhibitors of the organic anion transporting polypeptides (OATP) 1B1 and/or 1B3 may increase the plasma concentrations and effects of ezetimibe, which is a substrate of these hepatic uptake transporters. When a single dose of ezetimibe was taken with steady state bempedoic acid, a weak inhibitor of OATP1B1 and 1B3, the systemic exposure (AUC) and maximum plasma concentration (Cmax) of total ezetimibe (ezetimibe and its glucuronide form) increased by 1.6- and 1.8-fold, respectively. These increases were not considered clinically significant. When coadministered in patients on cyclosporine, a stronger OATP1B1 and 1B3 inhibitor, the AUC and Cmax of total ezetimibe increased by approximately 3.4- and 3.9-fold, respectively, compared to the exposure observed in a historical healthy control population. In another study, a renal transplant patient with severe renal dysfunction who was receiving multiple medications, including cyclosporine, demonstrated a 12-fold greater exposure to total ezetimibe compared to healthy subjects. The exact mechanism of the interaction with cyclosporine is unknown, but its ability to inhibit OATP1B1 and 1B3 may play a role. Data are not available for all inhibitors of OATP1B1 and/or 1B3 with ezetimibe.

MANAGEMENT: Caution and additional monitoring may be advisable if ezetimibe is used concurrently with OATP1B1 and/or 1B3 inhibitors. Additional monitoring of liver enzymes and creatine kinase (CK) may be necessary. Patients should also be advised to promptly report unexplained muscle pain, tenderness, or weakness to their healthcare provider.

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of telaprevir. When given with a meal containing 533 kcal and 21 g fat, telaprevir systemic exposure (AUC) increased by 237% compared to administration under fasting conditions. The type of meal also affects the exposure to telaprevir. Relative to fasting, telaprevir AUC increased by approximately 117% with a low-fat meal (249 kcal; 3.6 g fat) and 330% with a high-fat meal (928 kcal; 56 g fat). In Phase 3 clinical trials, telaprevir doses were administered within 30 minutes of completing a meal or snack containing approximately 20 grams of fat.

MANAGEMENT: Telaprevir should be administered with food containing approximately 20 grams of fat. Patients should be advised that the fat content of the meal or snack is critical to the absorption of telaprevir. Food taken with telaprevir should be ingested within 30 minutes prior to each dose. Examples of some foods that could be taken with telaprevir include: bagel with cream cheese; half cup of nuts; 3 tablespoons of peanut butter; 1 cup of ice cream; 2 ounces of American or cheddar cheese; 2 ounces of potato chips; or half cup of trail mix.