Ezetimibe

Overview
Ezetimibe 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 not 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. Ezetimibe was originally discovered by a team of four Schering-Plough research chemists; Drs. Stuart B. Rosenblum, Duane A. Burnett, John W. Clader and Brian A. McKittrick.

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 a critical mediator of cholesterol absorption, the Niemann-Pick C1-Like 1 (NPC1L1) protein on the gastrointestinal tract epithelial cells as well as in hepatocytes. 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.

Indications
Ezetimibe is indicated as an adjunct to dietary measures in the management of:
 * Hypercholesterolaemia
 * Homozygous sitosterolaemia (phytosterolaemia)

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.



Dosage forms
Ezetimibe is available as 10 mg tablets in most markets. A combination preparation ezetimibe/simvastatin, which combines ezetimibe with a statin, is also available.

Clinical Trial Controversy
On January 14, 2008, it was reported in the New York Times that a clinical trial of Zetia that was designed to show that the drug could reduce the growth of fatty plaques in arteries instead resulted in growth of plaques. Merck and Schering-Plough completed the clinical trial in April 2006 and had initially planned to release the findings no later than March 2007. The companies missed several self-imposed deadlines, and in December 2007 finally agreed to publish the results "soon" after the delays were publicized in news reports.