Drug Interactions between ezetimibe and Tykerb

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.