Ezetimibe 864202 221541651 2008-06-24T23:36:30Z Rjwilmsi 203434 gen fixes + format *date= in cite templates - full explanation [[User:Rjwilmsi#My_correction_of_dates_in_templates|here]] using [[Project:AutoWikiBrowser|AWB]] {{drugbox | | IUPAC_name = (3''R'',4''S'')-1-(4-fluorophenyl)-<br />3-((3''S'')-3-(4-fluorophenyl)-3-hydroxypropyl)-4-<br />(4-hydroxyphenyl)-2-azetidinone | image = Ezetimibe.png | width = 220 | CAS_number = 163222-33-1 | ATC_prefix = C10 | ATC_suffix = AX09 | PubChem = 150311 | DrugBank = APRD00619 | C=24 | H=21 | F=2 | N=1 | O=3 | molecular_weight = 409.4 g.mol<sup>-1</sup> | smiles = Oc1ccc(cc1)[C@@H]1[C@@H](CC[C@H](O)c2ccc(F)cc2)C(=O)N1c1ccc(F)cc1 | bioavailability = 35–65% | protein_bound = >90% | metabolism = Intestinal wall, hepatic | elimination_half-life = 19–30 hours | excretion = Renal 11%, faecal 78% | pregnancy_category = C <small>([[Australia|Au]])</small>, C <small>([[United States|U.S.]])</small> | legal_status = S4 <small>(Au)</small>, POM <small>([[United Kingdom|UK]])</small>, ℞-only <small>(U.S.)</small> | routes_of_administration = Oral }} '''Ezetimibe''' ({{pronEng|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 not tolerated, or together with [[statin]]s (e.g. [[ezetimibe/simvastatin]], marketed as '''[[Vytorin]]''' and '''[[Inegy]]''') when cholesterol levels are unable to be controlled on statins alone. It is marketed by [[Schering-Plough]] and [[Merck & Co.|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<ref name="Garcia-Calvo2005">Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, et al. The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). [[Proceedings of the National Academy of Sciences of the United States of America|Proc Natl Acad Sci U S A]] 2005;102(23):8132-7. PMID 15928087</ref> as well as in [[hepatocytes]]<ref name="Temel"> Temel, Ryan E., Tang, Weiqing, Ma, Yinyan, Rudel, Lawrence L., Willingham, Mark C., Ioannou, Yiannis A., Davies, Joanna P., Nilsson, Lisa-Mari, Yu, Liqing. Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe J. Clin. Invest. 2007 0: JCI30060</ref>. 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 [[sitosterolemia]] (phytosterolemia)<ref name="AMH2006">Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3 </ref> On [[9 June]] [[2006]], U.S. regulators approved the use of ezetimibe in combination with [[fenofibrate]] to treat [[hyperlipidemia|mixed hyperlipidaemia]]. ===Adverse effects=== Common [[adverse drug reaction]]s (≥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]] ([[alanine aminotransferase|ALT]]/[[aspartate aminotransferase|AST]]) results. Rarely (<0.1% of patients), [[hypersensitivity]] reactions (rash, [[angioedema]]) or [[myopathy]] may occur.<ref name="AMH2006" /> [[Image:zetia.gif|right|frame|Zetia Logo]] ===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]] (ENHANCE trial) of Zetia that was designed to show that the drug could reduce the growth of [[Atheromatous plaque|fatty plaques]] in arteries instead resulted in ''growth'' of plaques. However, the growth noted was less than it would have been had the patients been on placebo alone. 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.<ref name=nyt>{{cite news| url=http://www.nytimes.com/2008/01/14/business/14cnd-drug.html?em&ex=1200459600&en=fe4f047fcd65a68e&ei=5070 |title=Drug Has No Benefit in Trial, Makers Say|author= Berenson, A|publisher=NY Times|date=2008-01-14|accessdate=2008-01-14}}</ref> It should be recognized that the ENHANCE trial was not a clinical-outcome trial, but merely an imaging study. Formally, the American College of Cardiology (ACC) maintains that Zetia may be a reasonable option for patients who cannot tolerate a statin or cannot be controlled on a high dose statin. <ref name=acc>{{cite news| url=http://acc.org/enhance.htm|title=ACC Statement on ENHANCE Trial||publisher=ACC|date=2008-01-15|accessdate=2008-02-04}}</ref> Results from the trial have provoked three large clinical-outcome trials. The results from these trials will be presented in the next three to four years. However, a March 30th, 2008 meeting of the ACC resulted in negative press for drugs like Zetia as Yale University Cardiologist Harlan Krumholz and concurring colleagues called into question the efficacy of such drugs. <ref>{{cite news| url=http://www.businessweek.com/bwdaily/dnflash/content/mar2008/db20080331_704360.htm? |title=A Weak Prognosis for Vytorin and Zetia |author= Carey, J|publisher=Business Week|date=2008-03-31|accessdate=2008-04-01}}</ref> Krumholz' statements maintained that such pharmaceuticals should not be the first or even second option for prescribing doctors. Definitive conclusions of the efficacy and safety of Zetia can be made such a time when the results of more substantial and comprehensive trials are released. ==References== {{reflist}} ==See also== *[[Ezetimibe/simvastatin]] *[[Statin]] ==External links== *[http://www.zetia.com Zetia] *[http://www.zetia.com/ezetimibe/zetia/consumer/product_information/pi/index.jsp U.S. Prescribing Information] {{Merck&Co}} {{Lipid modifying agents}} [[Category:Hypolipidemic agents]] [[Category:Lactams]] [[de:Ezetimib]] [[it:Ezetimibe]] [[pl:Ezetymib]] [[pt:Ezetimiba]]