Pharmacology and therapeutics of ezetimibe (SCH 58235), a cholesterol-absorption inhibitor

Clin Ther. 2003 Sep;25(9):2352-87. doi: 10.1016/s0149-2918(03)80281-3.


Background: Ezetimibe is the first of a new class of antihyperlipidemic agents, the cholesterol-absorption inhibitors. It is indicated for monotherapy or in combination with 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitors (statins) in patients with primary hypercholesterolemia, in combination with simvastatin or atorvastatin in patients with homozygous familial hypercholesterolemia, and as monotherapy in patients with homozygous familial sitosterolemia.

Objective: This article reviews available data on the clinical pharmacology, clinical efficacy, and tolerability of ezetimibe.

Methods: A literature review was conducted using the search terms ezetimibe and SCH 58235 to identify articles and abstracts indexed in MEDLINE and the Iowa Drug Information Service from 1966 to February 2003. The reference lists of the identified articles were reviewed for additional publications.

Results: In adults, ezetimibe 10 mg PO given once daily has been reported to reduce intestinal cholesterol absorption by 54% from baseline in association with a compensatory increase in endogenous cholesterol synthesis. Within 2 weeks of its initiation, ezetimibe monotherapy produced a 17% to 20% reduction from baseline in low-density lipoprotein cholesterol (LDL-C); in combination with statins, ezetimibe produced a reduction in LDL-C of up to 40% over the same period. Based on studies performed to date, ezetimibe appears to be well tolerated, with a safety profile similar to that of placebo. Because ezetimibe is eliminated primarily by glucuronidation and not by cytochrome P450 (CYP) oxidation, it is subject to minimal drug interactions involving the CYP enzyme system.

Conclusions: Ezetimibe is an option for monotherapy in patients with mild hypercholesterolemia or in those requiring adjunctive drug therapy for reduction of LDL-C levels. It may be useful in patients at risk for adverse events (eg, liver toxicity, myopathy) from other hypocholesterolemic agents. Additive LDL-C-lowering effects of ezetimibe may allow use of lower doses of conventional agents (eg, statins, fibric acid derivatives, niacin) to achieve an equivalent effect, thereby reducing the potential for adverse events and drug interactions. However, because trials have lasted no longer than 12 weeks, the long-term effect of ezetimibe on cardiovascular morbidity and mortality remains to be determined.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / pharmacology
  • Anticholesteremic Agents / therapeutic use*
  • Azetidines / administration & dosage
  • Azetidines / pharmacology
  • Azetidines / therapeutic use*
  • Clinical Trials as Topic / statistics & numerical data
  • Drug Administration Schedule
  • Drug Interactions
  • Drug Therapy, Combination
  • Ezetimibe
  • Humans
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / metabolism
  • Lipoproteins / blood


  • Anticholesteremic Agents
  • Azetidines
  • Lipoproteins
  • Ezetimibe