• Fenofibrate and gemfibrozil both significantly increase ezetimibe levels when co-administered but this increase is not thought to be clinically significant.

• The UK manufacturers of ezetimibe state that the safety and efficacy of ezetimibe administered with fibrates have not been established and caution is advised. However, ezetimibe, administered in combination with fenofibrate is licensed in the USA as adjunctive therapy to diet in patients with mixed hyperlipidaemia. However, the US manufacturer states that co-administration of ezetimibe with fibrates other than fenofibrate is not recommended.

• Theoretically, co-administration may cause increased cholesterol excretion into the bile and raise the risk of cholelithiasis (gallstone formation). So, it may be prudent to avoid concomitant use of ezetimibe with any fibrate in a patient at high risk of cholelithiasis.

• Two small pharmacokinetic studies showed that total ezetimibe exposure is increased approximately 43% - 48% by fenofibrate but this was not considered to be clinically significant. The pharmacokinetics of fenofibrate were not affected. However, these findings may only apply to the fenofibrate formulations studied.

• One small pharmacokinetic study showed that gemfibrozil caused an approximately 1.7-fold increase in total ezetimibe exposure. However, this increase was not considered to be clinically significant. Gemfibrozil pharmacokinetics were not affected.

• Studies investigating the efficacy and safety of ezetimibe with bezafibrate have not been published in English. Co-administration of ezetimibe with ciprofibrate has not been studied.

 
• Further larger, long-term pharmacokinetic studies of ezetimibe co-administered with fibrates to patients with hypercholesterolaemia are required, particularly as results in healthy subjects may not always extrapolate well to patients.