Ezetimibe is a selective cholesterol absorption inhibitor that acts at the brush border of the small intestine. It localizes to the enterocyte and selectively inhibits the absorption of dietary and biliary cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction in hepatic cholesterol stores and an increase in clearance of cholesterol from the blood. It is used as monotherapy or in combination with statins for the management of hypercholesterolemia. In the Indian context, it is a key agent for patients intolerant to statins or requiring additional LDL-C lowering.
Adult: 10 mg once daily. The 5mg strength is often used in fixed-dose combinations (FDCs) with statins (e.g., Ezetimibe 5mg + Atorvastatin 10mg). As monotherapy, the standard dose is 10mg.
Note: Can be taken with or without food, at any time of the day. If used with a statin, both can be taken together. Should be taken as a single daily dose. For patients also taking bile acid sequestrants (e.g., cholestyramine), ezetimibe should be taken at least 2 hours before or 4 hours after the sequestrant.
Ezetimibe selectively and potently inhibits the Niemann-Pick C1-Like 1 (NPC1L1) protein, which is responsible for the uptake of intestinal cholesterol and phytosterols across the brush border membrane of the enterocytes in the small intestine. By blocking this transporter, it reduces the absorption of dietary and biliary cholesterol from the intestinal lumen.
Pregnancy: Pregnancy Category C (US FDA). Animal studies have shown adverse effects. There are no adequate and well-controlled studies in pregnant women. Ezetimibe is contraindicated during pregnancy because cholesterol and products of cholesterol biosynthesis are essential for fetal development. Discontinue immediately if pregnancy occurs.
Driving: Ezetimibe has no or negligible influence on the ability to drive and use machines. Dizziness and fatigue have been reported rarely.
| Cholestyramine | Reduces the bioavailability and systemic exposure of ezetimibe by approximately 55%. | Major |
| Fibrates (Gemfibrozil, Fenofibrate) | Increases ezetimibe concentration. May increase risk of cholelithiasis. Fibrates may increase cholesterol excretion into bile. | Major |
| Cyclosporine | Increases ezetimibe concentration (up to 12-fold). Increased risk of cyclosporine-induced side effects. Monitor cyclosporine levels. | Major |
| Warfarin | Minor, inconsistent effect on INR. Monitor INR when initiating or discontinuing ezetimibe. | Moderate |
| Statins (Atorvastatin, Simvastatin, Rosuvastatin) | Pharmacodynamic interaction: Additive LDL-C lowering. Pharmacokinetic interaction: Minimal. No significant effect on statin levels. | Minor (Therapeutic synergy) |