Drug Interactions between bempedoic acid/ezetimibe and rifampin

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.

MONITOR: Coadministration with bempedoic acid may increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of the uptake transporters organic anion transporting polypeptide (OATP) 1B1 and 1B3. The proposed mechanism, based on in vitro data, is decreased clearance due to bempedoic acid-mediated inhibition of OATP1B1 and 1B3.

MANAGEMENT: Caution is advised if bempedoic acid is used concomitantly with drugs that are substrates of OATP1B1 or 1B3, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever bempedoic acid is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.