Ezetimibe

This page contains recent news articles, when available, and an overview of Ezetimibe but does not offer medical advice. You should contact your physician with regard to any health issues or concerns.


Overview:

Ezetimibe
(when available)

Pharmacology and use:
Ezetimibe is in a class of lipid-lowering compounds that selectively inhibits the intestinal absorption of cholesterol and related phytosterols. Ezetimibe, administered alone is indicated as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and non-familial) hypercholesterolemia. It is also used in combination therapy with HMG-CoA reductase inhibitors. Ezetimibe has a mechanism of action that differs from those of other classes of cholesterol-reducing compounds (HMG-CoA reductase inhibitors, bile acid sequestrants, fibric acid derivatives, and plant stanols). Ezetimibe does not inhibit cholesterol synthesis in the liver, or increase bile acid excretion but instead localizes and appears to act at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood; this distinct mechanism is complementary to that of HMG-CoA reductase inhibitors. For use as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and non-familial) hypercholesterolemia.

Mechanism Of Action:
Ezetimibe localizes and appears to act at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver.

News Articles on Ezetimibe

Ezetimibe fallout: Experts discuss the premature release of ...  -  ‎Aug 13, 2009‎
Durham, NC - The unusual and controversial history of the cholesterol-lowering drug ezetimibe (Zetia, Merck/Schering-Plough) is the subject of special TheHeart.Org

Ezetimibe use 'should be last resort', DTB says  -  ‎Aug 17, 2009‎
By Nigel Praities GPs should 'make every effort' to lower cholesterol levels with statins rather than resort to using ezetimibe, an analysis by a BMJ Pulse

Rules Suggested for Premature Release of Trial Data  -  ‎Aug 12, 2009‎
A year after an analysis of early data from two ongoing trials of ezetimibe/simvastatin (Vytorin) was used to MedPage Today

Wall Street predicting win for extended-release niacin, but ...  -  ‎Aug 19, 2009‎
Although it is just speculation, clinicians also told heartwire they suspected a possible benefit of extended-release niacin over ezetimibe, TheHeart.Org

Concerned About Cholesterol?  -  ‎Aug 27, 2009‎
There is only one such drug--ezetimibe (Zetia). A 2003 study in the journal Pharmacotherapy found that when given alone or in combination with other KFSM

Merck, Schering agree to $41.5 million settlement of Vytorin ...  -  ‎Aug 6, 2009‎
...accused them of withholding unfavorable results of a clinical trial of the cholesterol drugs Vytorin [ezetimibe and simvastatin] and Zetia [ezetimibe]. InjuryBoard.com

Stockholders approve Merck & Co/Schering-Plough merger  -  ‎Aug 10, 2009‎
Last week, Merck and SP agreed to pay $41.5 million to settle class action litigation related to the cholesterol drugs Vytorin (ezetimibe/simvastatin) and Pharma Times

Glenmark confirms Smithkline's lawsuit in US  -  ‎Aug 18, 2009‎
Glenmark has four sole first-to-file products currently under litigation under the Hatch-Waxman Act. The other three products are Zetia(R) (Ezetimibe), Business Standard

US court to hear Glenmark's patent dispute on Aug 19  -  ‎Aug 6, 2009‎
The Indian drug maker is the sole first-to-file patent challenger for the $1.4 billion drug Zetia (Ezetimibe). As per the US rules, the first company to Economic Times

One Year On: Survey Of GP Opinion On The Impact Of NICE Guidelines ...  -  ‎Aug 19, 2009‎
Additional lipid lowering treatments available to GPs, such as changing to a more potent statin or adding in ezetimibe, should be considered. Medical News Today (press release)

L'ezetimibe funziona?  -  ‎Aug 9, 2009‎
Un articolo ulteriore che non chiarisce, anche per i bassi numeri in gioco, quali siano gli effetti di ezetimibe indipendenti da quelli delle statine, Pillole.org

"당뇨병 ë?™ë°˜ì§ˆí™˜ì?˜ 효과ì ?ì?¸ 치료와 ê·¸ 중요성"  -  ‎Aug 27, 2009‎
...�제티미브(ezetimibe)는 장관 벽� 존재하는 Niemann-Pick C1-like 1(NPC1L1)� 저해하여 콜레스테롤� �수를 선��으로 억제한다(그림 1). KMA Times

고지혈ì¦? 복합제 ë°”ì?´í† ë¦°, ê²½ìŸ?í’ˆ 비êµ? ìž„ìƒ?연구 중단 왜?  -  ‎Aug 21, 2009‎
...ì›?래 ë°”ì?´í† ë¦°ì?€ 머í?¬ì?˜ 심바스틴(simvastatin)ê³¼ ì‰?ë§?프ë?¼ìš°ì‚¬ì?˜ í•­ 콜레스테롤약 제티아(Ezetimibe)와ì?˜ 복합제로 개발ë?œ 약ì?´ë‹¤. 그러나 최근 ë°”ì?´í† ë¦°ì?˜ 비êµ? ìž„ìƒ? 쿠키뉴스

Changing the Diabetes Treatment Paradigm  -  13 Jul 2009
As we have seen with recent studies of ezetimibe and torcetrapib, our reliance on surrogate end points as markers for risk reduction is flawed. Archives of Internal Medicine

ARBITER-6 HALTS stopped early: Safety not an issue, but little ...  -  ‎Jul 9, 2009‎
Ezetimibe has been a flashpoint in the cardiology community since 2008, when the ENHANCE results were first presented. That trial showed that Vytorin, TheHeart.Org

Steering committee terminates ARBITER-6 HALT study prematurely  -  ‎Jul 10, 2009‎
Speculation over the reason for the trial's early termination reported in several media accounts included the possibility that ezetimibe outperformed niacin Cardiology Today

For Treatment of Dyslipidemia, Surveyed Physicians are ...  -  ‎Jul 8, 2009‎
Crestor --- rather than adding Merck/Schering-Plough's Zetia (ezetimibe) or switching to Merck/Schering-Plough's Vytorin (simvastatin/ezetimibe). PR Newswire (press release)

Merck & Co shares slip over Zetia/Niaspan trial termination  -  ‎Jul 10, 2009‎
The notice also stresses that the Phase IV study comparing Zetia (ezetimibe) and Niaspan (extended-release niacin) “was not stopped due to safety concerns�. Pharma Times

Glenmark gets first-to-file status for 3 drugs in US  -  ‎Jul 2, 2009‎
The latest first-to-file status was granted for Ezetimibe in April this year. Litigation for all three filings are in various stages, but if Glenmark wins, Economic Times

September 2008 Mayo Clinic Women's HealthSource Highlights Normal ...  -  ‎Jul 7, 2009‎
Researchers compared the drug ezetimibe-simvastatin (Vytorin), which combines a statin with a cholesterol-absorption inhibitor, with the stand-alone statin Chiropractic Economics

September 2004 Pharmaceutical Update  -  ‎Jun 29, 2009‎
Vytorin (ezetimibe/simvastatin) by Merck/Schering-Plough Pharmaceuticals in July was approved by the US Food and Drug Administration for the treatment of ADVANCE for Physician Assistants

NeoStem, Inc. Appoints International Expert in Endocrinology and ...  -  ‎Jul 6, 2009‎
NJ, where he was involved in the joint venture with Merck in the clinical development of the novel cholesterol medication, ezetimibe (Zetia). PR Newswire (press release)

Vitamin D has many benefits  -  ‎Jun 20, 2009‎
...thiazide diuretics, corticosteroids, nicotine, cimetidine, cholesterol-lowering agents (ezetimibe), heparin, and diet agents (Xenical and Alli). fwdailynews.com

L-TAP 2: Number of patients lowering LDL nearly doubled in the ...  -  ‎Jun 23, 2009‎
Others took fibrates, ezetimibe (Zetia, Merck-Schering Plough) or incorporated lifestyle changes such as diet and exercise without a drug. Endocrine Today

Prueban novedosa terapia capaz de prevenir los cálculos biliares  -  ‎Jun 22, 2009‎
Investigadores de la U. Católica, liderados por el profesor del Depto. de Gastroenterología, Juan Francisco Miquel, descubrieron que el ezetimibe, El Mercurio (Chile)

제티아, 니아스íŒ? 비êµ?ìž„ìƒ? '기권'  -  ‎Jul 9, 2009‎
...머í?¬ì?˜ 제티아와(Zetia, ezetimibe) 애보트ì?˜ 니아스íŒ?(Niaspan, niacin)ì?˜ 효과를 비êµ?하는 ìž„ìƒ?시험ì?´ ë?Œì—° 중단ë?¼, 제티아가 효과 부족으로 기권한 것ì?´ 아니ëƒ?는 디지틀보사

Le statine appaiono generalmente inefficaci nel ritardare la ...  -  ‎Jul 7, 2009‎
Lo studio SEAS ( Simvastatin and Ezetimibe in Aortic Stenosis ), non solo ha trovato che le statine non hanno un significativo effetto sulla progressione Cardiologia.net

NeoStem, Inc. 任命内分泌和è?¯ç?†å­¦é¢†åŸŸçš„国际专家担任其è?¯ç‰©å¼€å?‘与监管 ...  -  ‎Jul 6, 2009‎
...事务部(Medical & Scientific Affairs) 高级主管,期间,他å?‚与了与默克公å?¸(Merck) è?”å?ˆåˆ›åŠžçš„å?ˆèµ„ä¼?业在新型胆固醇è?¯ç‰©ezetimibe (Zetia) 领域的临床开å?‘工作。 凤凰网

Prewencja chorób sercowo-naczyniowych - postÄ™py 2008  -  ‎Jun 18, 2009‎
Ezetimibe monotherapy for cholesterol lowering in 2722 people: systematic review and meta-analysis of randomized controlled trials. J. Intern. Medycyna Praktyczna

NeoStem, Inc. 任命內分泌和藥ç?†å­¸é ˜åŸŸçš„國際專家擔任其藥物開發與監管 ...  -  ‎Jul 6, 2009‎
...事務部(Medical & Scientific Affairs) 高級主管,期間,他å?ƒèˆ‡äº†èˆ‡é»˜å…‹å…¬å?¸(Merck) è?¯å?ˆå‰µè¾¦çš„å?ˆè³‡ä¼?業在新型膽固醇藥物ezetimibe (Zetia) 領域的臨床開發工作。 臺灣新浪網

Skuteczność i bezpieczeÅ„stwo leczenia ezetymibem w połączeniu z ...  -  ‎Jul 6, 2009‎
Lipid-altering efficacy and safety of ezetimibe/simvastatin versus atorvastatin in patients with hypercholesterolemia and the metabolic syndrome (from the Polskie Towarzystwo Kardiologiczne

Zetia and Vytorin Side Effects Not Linked to Cancer According to Study  -  ‎Mar 30, 2009‎
Zetia (ezetimibe) is a prescription drug which decreases cholesterol delivery to the liver by inhibiting its intestinal absorption. Vytorin is a combination AboutLawsuits.com

2-in-1: Merck and Schering-Plough  -  ‎Apr 8, 2009‎
Zetia (ezetimibe) was launched in 2003, and is the first in a new class of cholesterol lowering drugs which works by blocking the body's absorption of Pharmafocus

Evaluating and Understanding Articles About Treatment  -  ‎Apr 15, 2009‎
Cholesterol lowering and ezetimibe. N Engl J Med. 2008; 358(14):1507-1508. 4. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial AAFP News Now

Sunset for Statins after AURORA?  -  ‎Mar 30, 2009‎
Since SHARP is evaluating the effect of combined simvastatin–ezetimibe therapy, it is concerned with an overlapping but different research question. New England Journal of Medicine (subscription)

A cuidarse ese colesterol  -  ‎Apr 19, 2009‎
Debido a todos esos factores, tenemos otra herramienta: Ezetimibe. Con esa droga, que tiene un mecanismo de acción diferente, se evita que el colesterol que Correo del Caroní

위기 'MSD ë°”ì?´í† ë¦°' 기사회ìƒ? 길 ë³´ì?´ë‚˜  -  ‎Apr 13, 2009‎
...ì?´ëŠ” 지난해 9ì›” 발표ë?œ SEAS(Simvastatin and Ezetimibe in Aortic Stenosis) 연구ì—?서 ë°”ì?´í† ë¦°ì?´ 위약 대비 발암 위험성ì?´ ì¦?가했다는 보고와는 ìƒ?ë°˜ë?œ 결과다. 데일리메디

ë°”ì?´í† ë¦°, ì•” ë°˜ì?‘ 1백만건 당 1.3회 불과  -  ‎Apr 8, 2009‎
...ì?´ ê°™ì?€ 결과는 2008ì›” 9ì›” SEAS(Simvastatin and Ezetimibe in Aortic Stenosis) ìž„ìƒ? ê²°ê³¼ 발표 ì?´í›„ 제기ë?œ ì—?제티미브와 ì—?제티미브/심바스타틴 복합제(ë°”ì?´í† ë¦°) 메디팜뉴스

Rosuvastatina nei pazienti in emodialisi  -  ‎Apr 9, 2009‎
...che ha arruolato circa 9000 pazienti con insufficienza renale cronica (in dialisi e non) e che sta testando l'associazione simvastatina/ezetimibe. Pillole.org

全世界引用率最高的医学论文  -  ‎Apr 2, 2009‎
77 JJP Kastelein, et al., "Simvastatin with or without ezetimibe in familial hypercholesterolemia," New Engl. J. Med., 358(14): 1431-3, 3 April 2008. 科讯网

Brand Names/Synonyms:
Ezetimibe is also known by the following brand names and/or synonymsEzedoc; Ezetimibe; Ezetimibe [Usan:Inn]; Ezetimibe [Usan]; Vytorin; Zetia

Drug Category:
Ezetimibe is categorized under the following by the FDA: Anticholesteremic Agents; Cholesterol Absorption Inhibitors; ATC:C10AX09

Dosage Forms:
TABLET

Absorption:
Not Available

Interactions:
-->Interactions for Ezetimibe:

Cholestyramine: Concomitant cholestyramine administration decreased the mean AUC of total ezetimibe approximately 55%. The incremental LDL-C reduction due to adding ezetimibe to cholestyramine may be reduced by this interaction.

Fibrates: The safety and effectiveness of ezetimibe administered with fibrates have not been established.

Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis. In a preclinical study in dogs, ezetimibe increased cholesterol in the gallbladder bile. Co-administration of ZETIA with fibrates is not recommended until use in patients is studied.

Fenofibrate: In a pharmacokinetic study, concomitant fenofibrate administration increased total ezetimibe concentrations approximately 1.5-fold.

Gemfibrozil: In a pharmacokinetic study, concomitant gemfibrozil administration increased total ezetimibe concentrations approximately 1.7-fold.

HMG-CoA reductase inhibitors: No clinically significant pharmacokinetic interactions were seen when ezetimibe was co-administered with atorvastatin, simvastatin, pravastatin, lovastatin, or fluvastatin.

Cyclosporine: The total ezetimibe level increased 12-fold in one renal transplant patient receiving multiple medications, including cyclosporine. Patients who take both ezetimibe and cyclosporine should be carefully monitored.

Carcinogenesis, Mutagenesis, Impairment of Fertility

A 104-week dietary carcinogenicity study with ezetimibe was conducted in rats at doses up to 1500 mg/kg/day (males) and 500 mg/kg/day (females) (~20 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). A 104-week dietary carcinogenicity study with ezetimibe was also conducted in mice at doses up to 500 mg/kg/day (>150 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). There were no statistically significant increases in tumor incidences in drug-treated rats or mice.

No evidence of mutagenicity was observed in vitro in a microbial mutagenicity (Ames) test with Salmonella typhimurium and Escherichia coli with or without metabolic activation. No evidence of clastogenicity was observed in vitro in a chromosomal aberration assay in human peripheral blood lymphocytes with or without metabolic activation. In addition, there was no evidence of genotoxicity in the in vivo mouse micronucleus test.

In oral (gavage) fertility studies of ezetimibe conducted in rats, there was no evidence of reproductive toxicity at doses up to 1000 mg/kg/day in male or female rats (~7 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe).

Pregnancy

Pregnancy Category: C

There are no adequate and well-controlled studies of ezetimibe in pregnant women. Ezetimibe should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

In oral (gavage) embryo-fetal development studies of ezetimibe conducted in rats and rabbits during organogenesis, there was no evidence of embryolethal effects at the doses tested (250, 500, 1000 mg/kg/day). In rats, increased incidences of common fetal skeletal findings (extra pair of thoracic ribs, unossified cervical vertebral centra, shortened ribs) were observed at 1000 mg/kg/day (~10 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). In rabbits treated with ezetimibe, an increased incidence of extra thoracic ribs was observed at 1000 mg/kg/day (150 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). Ezetimibe crossed the placenta when pregnant rats and rabbits were given multiple oral doses.

Multiple dose studies of ezetimibe given in combination with HMG-CoA reductase inhibitors (statins) in rats and rabbits during organogenesis result in higher ezetimibe and statin exposures. Reproductive findings occur at lower doses in combination therapy compared to monotherapy.

All HMG-CoA reductase inhibitors are contraindicated in pregnant and nursing women. When ZETIA is administered with an HMG-CoA reductase inhibitor in a woman of childbearing potential, refer to the pregnancy category and package labeling for the HMG-CoA reductase inhibitor.

Labor and Delivery

The effects of ZETIA on labor and delivery in pregnant women are unknown.

Nursing Mothers

In rat studies, exposure to total ezetimibe in nursing pups was up to half of that observed in maternal plasma. It is not known whether ezetimibe is excreted into human breast milk; therefore, ZETIA should not be used in nursing mothers unless the potential benefit justifies the potential risk to the infant.

Pediatric Use

The pharmacokinetics of ZETIA in adolescents (10 to 18 years) have been shown to be similar to that in adults. Treatment experience with ZETIA in the pediatric population is limited to 4 patients (9 to 17 years) in the sitosterolemia study and 5 patients (11 to 17 years) in the HoFH study. Treatment with ZETIA in children (<10 years) is not recommended.

Geriatric Use

Of the patients who received ZETIA in clinical studies, 948 were 65 and older (this included 206 who were 75 and older). The effectiveness and safety of ZETIA were similar between these patients and younger subjects. Greater sensitivity of some older individuals cannot be ruled out.





Chemical IUPAC Name:
1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxy-propyl]-4-(4-hydroxyphenyl)-azetidin-2-one

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