Drug Interactions between bempedoic acid/ezetimibe and fenofibrate

MONITOR: Concomitant use of ezetimibe may potentiate the risk of cholelithiasis associated with fenofibrate and other fibrates. Fibrates can increase cholesterol excretion into the bile and cause cholelithiasis. A study comparing fenofibrate monotherapy (n=188) to ezetimibe combined with fenofibrate (n=183) found incidence rates for cholecystectomy were numerically higher in the combination group (0.6% vs 1.7%). In a study of 32 adult subjects with low-density lipoprotein cholesterol (LDL-C) levels of greater than or equal to 130 mg/dL, coadministration with fenofibrate (200 mg once daily) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of total ezetimibe by approximately 64% and 48%, respectively. Fenofibrate's Cmax and AUC were increased by 7% and 11%, respectively. The increases in total ezetimibe and fenofibrate are not considered clinically relevant. Similarly, when fenofibric acid delayed-release capsules (135 mg once daily) were coadministered with ezetimibe (10 mg once daily) for 10 days, the AUC of fenofibric acid was also not significantly increased and the AUC of total ezetimibe increased by only 27%.

MANAGEMENT: Caution and increased monitoring are advised during coadministration of ezetimibe and fenofibrate. This recommendation may also apply if ezetimibe is administered with fenofibric acid. If cholelithiasis is suspected, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered. Some authorities consider concomitant use of ezetimibe and fenofibrate to be contraindicated in patients with preexisting gallbladder disease.