Ezentia Drug Interactions

(See Pharmacology: Pharmacokinetics under Actions).
It has been reported that ezetimibe does not induce cytochrome P450 drug metabolising enzymes. No clinically significant pharmacokinetic interactions have been reported between ezetimibe and drugs known to be metabolized by cytochromes P450 1A2, 2D6, 2C8, 2C9, and 3A4, or N-acetyltransferase.
Ezetimibe had no effect on the pharmacokinetics of dapsone, dextromethorphan, digoxin, oral contraceptives (ethinyl estradiol and levonorgestrel), glipizide, tolbutamide, or midazolam, during co-administration. Cimetidine, co-administered with ezetimibe, had no effect on the bioavailability of ezetimibe.
Antacids: Concomitant antacid administration decreased the rate of absorption of ezetimibe but had no effect on the bioavailability of ezetimibe. This decreased rate of absorption is not considered clinically significant.
Cyclosporine: Caution should be exercised when using ezetimibe and cyclosporine concomitantly due to increased exposure to both ezetimibe and cyclosporine. Cyclosporine concentrations should be monitored in patients receiving ezetimibe and cyclosporine.
The degree of increase in ezetimibe exposure may be greater in patients with severe renal insufficiency. In patients treated with cyclosporine, the potential effects of the increased exposure to ezetimibe from concomitant use should be carefully weighed against the benefits of alterations in lipid levels provided by ezetimibe.
Fibrates: The efficacy and safety of co-administration of ezetimibe with fibrates other than fenofibrate have not been reported.
Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis. It was reported that in dogs, ezetimibe increased cholesterol in the gallbladder bile [see Pharmacology: Toxicology: Preclinical Saftey Data under Actions). Coadministration of ezetimibe with fibrates other than fenofibrate is not recommended until use in patients is adequately reported.
Fenofibrate: If cholelithiasis is suspected in a patient receiving ezetimibe and fenofibrate, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered (see Adverse Effects and the prescribing information for fenofibrate).
Statins: No clinically significant pharmacokinetic interactions were reported when ezetimibe was co-administered with atorvastatin, simvastatin, pravastatin, lovastatin, fluvastatin or rosuvastatin.
Cholestyramine: Concomitant cholestyramine administration decreased the mean area under the curve (AUC) of total ezetimibe approximately 55%. The incremental LDL-C reduction due to adding ezetimibe to cholestyramine may be reduced by this interaction.
Anticoagulants: Concomitant administration of ezetimibe (10 mg once daily) had no significant effect on bioavailability of warfarin and prothrombin time in a study of twelve healthy adult males. However, there have been post-marketing reports of increased International Normalised Ratio (INR) in patients who had ezetimibe added to warfarin or fluindione. If ezetimibe is added to warfarin, another coumarin anticoagulant, or fluindione, the International Normalized Ratio (INR) should be appropriately monitored.