Pharmacology · Cholesterol absorption inhibitors

Ezetimibe !

Blocks cholesterol absorption in the gut. Added to a statin it lowers LDL further; it is the usual first add-on to a statin.

Updated 2026-11-01

Class: Cholesterol absorption inhibitors
Transporter: NPC1L1 sterol transporter
ATC code: C10AX09

NPC1L1 sterol transporterEzetimibe

The figure shows ezetimibe bound to human NPC1L1 (cryo-EM, construct without the N-terminal domain); cholesterol molecules also appear in the structure.

Target in 3D: NPC1L1 sterol transporter. PDB structure 7DFZ (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Ezetimibe and its active glucuronide localize at the brush border of the small intestine and bind NPC1L1, the transporter that takes cholesterol and plant sterols into enterocytes. Less cholesterol reaches the liver in chylomicron remnants, hepatic cholesterol falls and LDL receptors increase, lowering blood LDL. The liver responds by synthesizing more cholesterol, which a statin can block.

Binds NPC1L1 on the intestinal brush border
Less dietary and biliary cholesterol is absorbed
Liver cholesterol falls and LDL receptors rise
Blood LDL falls, more so with a statin

Pharmacokinetics

Absorption: Oral; rapidly converted in the intestine and liver to an active glucuronide.
Metabolism: Glucuronide conjugation, with very little oxidative (CYP) metabolism.
Elimination: In bile and urine; repeated plasma peaks reflect enterohepatic recycling.
Half-life: About 22 hours for ezetimibe and its glucuronide.

Indications

High LDL cholesterol, alone or added to a statin, including in secondary prevention Atherosclerosis and dyslipidaemia →
Familial hypercholesterolemia (heterozygous and homozygous), with a statin Familial hypercholesterolemia →
Homozygous sitosterolemia (plant-sterol overabsorption)

Adverse effects

Common

Diarrhea, upper respiratory infection symptoms
Joint pain, muscle aches
Raised transaminases, mainly combined with a statin

Contraindications

Hypersensitivity to ezetimibe or an excipient
When combined with a statin or fenofibrate: every contraindication of that partner drug

Key interactions

Colestyramine and other bile acid sequestrants: Bind ezetimibe and lower its exposure; ezetimibe is given at least 2 hours before or 4 hours after.
Cyclosporine: Raises ezetimibe exposure, and ezetimibe can raise cyclosporine levels; cyclosporine levels are monitored.
Fibrates: Both may increase cholesterol in bile; with fenofibrate the gallstone risk is kept in mind. Other fibrates are not combined.

What is monitored

Lipid panel before and some weeks after starting
Liver enzymes when combined with a statin, as the statin label indicates
Muscle symptoms

Administration and safety

Oral tablet once daily, with or without food, at any time of day.
Given at least 2 hours before or 4 hours after a bile acid sequestrant.
Often in a fixed combination with a statin: the statin component sets the interaction checks.

Nursing care

Before: lipid panel and the full medication list (statin, sequestrant, cyclosporine).
Ask about unexplained muscle pain or weakness.
Teach that diet and the statin continue; ezetimibe adds to them.
Check timing with any resin powder the patient also takes.

Pregnancy and breastfeeding

Few human data; when it is combined with a statin, the statin's pregnancy rule applies and the combination is not used in pregnancy.

Test yourself

Think of the answer, then tap the question to see it.

What is ezetimibe's molecular target?

NPC1L1, the sterol transporter on the brush border of the small intestine.

Why does ezetimibe have a long half-life even though it is quickly glucuronidated?

The active glucuronide is excreted in bile and reabsorbed (enterohepatic recycling), giving a half-life of about 22 hours.

A patient takes ezetimibe and colestyramine in the morning together. What is the problem?

The resin binds ezetimibe in the gut and lowers its absorption; ezetimibe is given at least 2 hours before or 4 hours after.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Ezetimibe: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - EZETIMIBE tablet (DailyMed (U.S. National Library of Medicine), 2026); Cryo_EM structure of delta N-NPC1L1-EZE (RCSB Protein Data Bank, 2021); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.