Article: Ezetimibe

Ezetimibe
Systematic (IUPAC) name
(3R,4S)-1-(4-fluorophenyl)- 3-((3S)-3-(4-fluorophenyl)-3-hydroxypropyl)-4- (4-hydroxyphenyl)-2-azetidinone
Identifiers
CAS number	163222-33-1
ATC code	C10AX09
PubChem	150311
DrugBank	APRD00619
Chemical data
Formula	C24H21NF2O3
Mol. weight	409.4 g.mol-1
Pharmacokinetic data
Bioavailability	35–65%
Protein binding	>90%
Metabolism	Intestinal wall, hepatic
Half life	19–30 hours
Excretion	Renal 11%, faecal 78%
Therapeutic considerations
Pregnancy cat.	C (Au), C (U.S.)
Legal status	S4 (Au), POM (UK), ℞-only (U.S.)
Routes	Oral

Ezetimibe (IPA: [ɛˈzɛtəmɪb]) is an anti-hyperlipidemic medication which is used to lower cholesterol levels. It acts by decreasing cholesterol absorption in the intestine. It may be used alone when other cholesterol-lowering medications are unable to be tolerated, or together with statins (e.g. ezetimibe/simvastatin) when cholesterol levels are unable to be controlled on statins alone. It is marketed by Schering-Plough and Merck under the trade names Ezetrol, Zetia and Ezemibe.

Pharmacology

Ezetimibe localises at the brush border of the small intestine, where it inhibits the absorption of cholesterol from the diet. Specifically, it appears to bind to the Niemann-Pick C1-Like 1 (NPC1L1) protein on the gastrointestinal tract epithelium, a critical mediator of cholesterol absorption.^[1] In addition to this direct effect, decreased cholesterol absorption leads to an increase in LDL-cholesterol uptake into cells, thus decreasing levels in the blood plasma.

Clinical use

Indications

Ezetimibe is indicated as an adjunct to dietary measures in the management of:

• Hypercholesterolaemia
• Homozygous sitosterolaemia (phytosterolaemia)^[2]

On 9 June 2006, U.S. regulators approved the use of ezetimibe in combination with fenofibrate to treat mixed hyperlipidaemia.

Adverse effects

Common adverse drug reactions (≥1% of patients) associated with ezetimibe therapy include: headache and/or diarrhea. Infrequent adverse effects (0.1–1% of patients) include: myalgia and/or raised liver function test (ALT/AST) results. Rarely (<0.1% of patients), hypersensitivity reactions (rash, angioedema) or myopathy may occur.^[2]

Dosage forms

Zetia Logo

Ezetimibe is available as 10 mg tablets in most markets, with 5 mg and 20 mg tablets also being available on the U.S. market. A combination preparation ezetimibe/simvastatin, which combines ezetimibe with a statin, is also available.