Ezetimibe

Ezetimibe is a lipid‑lowering medication that inhibits the absorption of cholesterol from the small intestine. It is used to reduce elevated LDL cholesterol and total cholesterol, either as monotherapy or in combination with a statin (for example, in a regimen marketed as ezetimibe with simvastatin). It is approved for use in adults and in pediatric patients aged 10 years and older with primary hyperlipidemia or mixed dyslipidemia, and it may also be used in certain cases of sitosterolemia to limit intestinal uptake of plant sterols.

Mechanism of action: Ezetimibe selectively blocks the Niemann-Pick C1‑like 1 (NPC1L1) transporter on enterocytes, reducing intestinal cholesterol and phytosterol absorption. This lowers the amount of cholesterol delivered to the liver, which in turn upregulates hepatic LDL receptors and lowers circulating LDL cholesterol. The drug has a modest effect when used alone and a greater effect when combined with statins.

Pharmacokinetics and administration: Ezetimibe is taken orally and is rapidly absorbed; it is extensively glucuronidated to an active ezetimibe glucuronide metabolite. Both forms contribute to lipid lowering. It is primarily excreted via bile into the feces, with a terminal half‑life of about 22 hours for the active metabolite. The usual dose is 10 mg once daily, with adjustments when used with other lipid‑lowering agents.

Adverse effects and considerations: Common adverse effects include gastrointestinal symptoms such as diarrhea or abdominal pain. Elevations in liver enzymes may occur, especially when combined with a statin. Rare hypersensitivity reactions and muscle symptoms can occur. It should be avoided in active liver disease or significant hepatic impairment and used with caution in pregnancy and breastfeeding. Interactions include reduced ezetimibe absorption with bile acid sequestrants; dosing should be separated by several hours. Cyclosporine can increase ezetimibe exposure.