Ezetimibe/simvastatin 1004541 217670121 2008-06-07T02:56:52Z Endtothemeans 3893984 Removed "clever" before "TV ads". This is subjective. {{Drugbox | type = combo | image = Ezetimibe.png | width = 220px | image2 = Simvastatin.png | width2 = 171px | component1 = Ezetimibe | class1 = via [[Niemann-Pick C1-Like 1]] protein | component2 = Simvastatin | class2 = [[Statin]] [[HMG-CoA reductase]] inhibitor | CAS_number = | ATC_prefix = C10 | ATC_suffix = BA02 | PubChem = | DrugBank = | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_US = <!-- A / B / C / D / X --> | pregnancy_category= | legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> | legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_UK = <!-- GSL / P / POM / CD / Class A, B, C --> | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | legal_status = Rx | routes_of_administration = Oral }} '''Ezetimibe/simvastatin''' ({{pronEng|ɛˌzɛtɨmɪb ˌsɪmvəˈstætɨn}}) is a drug combination used for the treatment of [[dyslipidemia]]. It is a combination of [[ezetimibe]] (best known as '''Zetia''' in the [[United States]]) and the [[statin]] drug [[simvastatin]] (best known as '''Zocor''' in the U.S.). The combination preparation is marketed by [[Merck & Co.]]/[[Schering-Plough]] Pharmaceuticals (joint venture) under the trade names '''Vytorin''' and '''Inegy'''. [[Ezetimibe]] reduces blood cholesterol by inhibiting absorption of cholesterol by the small intestine by acting 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. [[Simvastatin]] is an [[HMG-CoA reductase]] inhibitor or [[statin]]. It works by blocking an [[enzyme]] that is necessary for the body to make cholesterol. ==Pharmacology== The combination of Ezetimibe and Simvastatin is the only product to treat both sources of cholesterol; absorption in the intestine of both biliary and dietary cholesterol, and production in the liver and peripheral tissues.<ref>[http://www.medicalnewstoday.com/articles/50877.php Physicians Agree That Treating Two Sources Of Cholesterol Likely To Achieve Greater LDL-Cholesterol Reductions<!-- Bot generated title -->]</ref> It is thought that the treatment of high cholestrol from both sources is likely to result in lower cholesterol levels,<ref>[http://www.medicalnewstoday.com/articles/50877.php Physicians Agree That Treating Two Sources Of Cholesterol Likely To Achieve Greater LDL-Cholesterol Reductions<!-- Bot generated title -->]</ref> particularly [[LDL]] cholesterol. In a clinical study, it was shown that the combination of Ezetimibe and Simvastatin was superior to [[Lipitor]] in lowering LDL cholestrol.<ref>[http://www.medicalnewstoday.com/articles/15694.php VYTORIN could lower bad cholesterol (LDL-C) more than Lipitor, New Trial Shows<!-- Bot generated title -->]</ref> ==Clinical trials== ===ENHANCE trial data=== The two year ENHANCE Study, released by the manufacturer as an abstract,<ref>[http://www.sch-plough.com/schering_plough/news/release.jsp?releaseID=1095943 Schering-Plough - News and Media - News Releases<!-- Bot generated title -->]</ref> recently failed to provide evidence that ezetimibe/simvastatin was better than [[simvastatin]] (a generic medication) in terms of achieving a lower change from baseline in [[intima-media thickness|carotid intima-media thickness]] despite lower LDL levels in a population of patients with heterozygous familial hypercholesterolemia (a form of high cholesterol that affects less than 1% of patients). Clinical events such as heart attack and stroke were not measured as primary or secondary endpoints of the study making it impossible to determine Vytorin's effect on these events.<ref>[http://www.time.com/time/health/article/0,8599,1703827,00.html Is Vytorin a Failure? - TIME<!-- Bot generated title -->]</ref> Data from studies specifically designed to answer this question are expected within the next few years. ===Subsequent debate and enquiries=== The American College of Cardiology released a statement suggesting that "major clinical decisions not be made on the basis of the ENHANCE study alone", given the small and unique patient population, 720 patients in an Amsterdam hospital with heterozygous familial hypercholesterolemia. <ref>[http://www.medicalnewstoday.com/articles/94103.php Vytorin Results Disappointing, Experts Say Don't Panic<!-- Bot generated title -->]</ref> Merck and Schering Plough have reported that they have three trials underway to focus on outcomes, measuring the drug's effect on heart attacks and strokes in patients.<ref>[http://www.time.com/time/health/article/0,8599,1703827,00.html Is Vytorin a Failure? - TIME<!-- Bot generated title -->]</ref> The results of the ENHANCE study have been long anticipated. These results were presented in full at the [[American College of Cardiology]] meeting on 30 March 2008. The [[United States House Committee on Energy and Commerce|House Committee on Energy and Commerce]] has started an inquiry into the delayed disclosure of the study data;<ref>http://www.forbes.com/feeds/ap/2007/12/12/ap4433892.html</ref> In addition there is an ongoing investigation into [[Carrie Smith Cox]], Schering-Plough’s president, who sold 900,000 shares of company stock in April and May of 2007 worth an estimated $28 million. This massive sell off comes after the ENHANCE trial was complete.<ref>[http://www.pharmalot.com/2008/01/congress-to-probe-vytorin-insider-stock-sales/ Pharmalot » Congress To Probe Vytorin Insider Stock Sales<!-- Bot generated title -->]</ref> Finally there is an inquiry into the popular Vytorin brand, direct-to-consumer (DTC) ads. The companies continued spending at least $155 million a year on TV ads that heralded Vytorin’s supposed superiority over statins alone, while withholding the ENHANCE results.<ref>[http://www.newsinferno.com/archives/2406 Vytorin Ads Scrutinized by Lawmakers<!-- Bot generated title -->]</ref> ===IMPROVE-IT trial=== Vytorin is currently undergoing another randomized control trial (IMPROVE-IT). This trial will measure the effects of Vytorin vs. simvastatin alone in determining primary outcomes of cardiovascular and cerebrovascular events in 18,000 patients who have been hospitalized for an acute coronary syndrome. The patients will be followed for a minimum of 2.5 years. The trial is expected to end in 2012.<ref>[http://clinicaltrials.gov/show/NCT00202878 IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome:Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (Study P04103)]</ref> ==Advertising campaign== In the United States, the Vytorin brand has become rather well known for its television advertising campaign showing a series of split-screen images of a person and a food item to make the point that cholesterol comes from two sources and can be absorbed from food or manufactured by the body, and that heredity plays a role in the latter.<ref>[http://www.tvweek.com/news/2007/10/chart_mostrecalled_new_prescri.php Chart: Most-Recalled New Prescription Drug Ads 2006-07 TV Season - TVWeek - News<!-- Bot generated title -->]</ref> This point is a departure from the commonly held belief that high cholestrol only comes from the food that you eat.<ref>[http://www.medicalnewstoday.com/articles/10750.php Most Americans do not know that high cholesterol comes from two sources<!-- Bot generated title -->]</ref> In each commercial, the person is dressed, and the food plated, to emphasize the resemblance between the person and the food. Some examples include: * A woman wearing a yellow shirt with a red and green pin intended to look like a taco. * A man wearing a white shirt with a green bow tie intended to look like a plate of pasta topped with peas. * A woman wearing a yellow blouse with a decorative white fringe around the neck line intended to look like some sort of lemon pie surrounded with whipped cream and cookies (the cookies being the same yellow as the blouse) * An older gentleman with rather spiky white hair intended to look like a lamb chop (with the bones of the lamb chop resembling the spiky white hair) * A woman in a red diving suit carrying large flippers, intended to look like a lobster. * A woman in a suit with red and white swirls, intended to look like a cheese cake topped with a red swirled topping. * A man in a brown jacket and helmet of some kind, with bright yellow goggles, intended to resemble pancakes with a similarly yellow topping of butter or margarine. * An [[African-American]] man with a black hat, and a brown and white sweater to represent a brownie with ice cream. ==Contraindications== * Acute liver disease * Pregnancy and breast feeding ==Side effects== * [[Myopathy]] * [[Rhabdomyolysis]] * [[Myalgia]] * Pain in extremities, abdomen, * [[Angioedema]] * [[Hepatitis]] * [[Eczema]] * [[Fatigue (medical)|Fatigue]] * Headache * Influenza, [[Pharyngitis]], [[sinusitis]] and upper respiratory tract infection * Depression.<ref>[http://money.cnn.com/news/newsfeeds/articles/djf500/200802141551DOWJONESDJONLINE001013_FORTUNE5.htm/ Depression Added as Possible Side Effect<!-- Bot generated title -->]</ref> ==Interactions== * [[Cyclosporine]] * [[Danazol]] * [[Protease inhibitors]] * [[Verapamil]] * [[Amiodarone]] * Large amounts of [[niacin]] (nicotinic acid), [[grapefruit]] juice * [[Erythromycin]], [[telithromycin]], [[clarithromycin]] * [[Nefazodone]] ==References== {{Reflist|2}} ==External links== * [http://www.vytorin.com Vytorin's Official Site] * [http://www.medsafe.govt.nz/profs/datasheet/v/Vytorintab.htm Vytorin Information Sheet] * [http://www.kansas.com/188/story/281569.html] {{Merck&Co}} {{Statins}} [[Category:Statins]] [[simple:Vytorin]]