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Zocor |
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Simvastatin
(INN) is a hypolipidemic drug belonging to the class of
pharmaceuticals called "statins". It is used to control
hypercholesterolemia (elevated cholesterol levels) and to prevent
cardiovascular disease. Simvastatin is a synthetic derivate of a
fermentation product of Aspergillus terreus. Brand names: Zocor, Zocor Heart Pro (Germany), Liponorm, Sinvacor, Sivastin (Italy), Lipovas (Japan), Lodales (France), Zocord (Austria and Sweden), Zimstat, Simvahexal (Australia), Lipex (Australia and New Zealand), Simvacor, Simvaxon, Simovil (Israel), Simvotin (India) and other. Uses Simvastatin is a powerful lipid-lowering drug that can decrease low density lipoprotein (LDL) levels by up to 50%. It is used in doses of 5 mg up to 80 mg. Higher doses (160 mg) have been found to be too toxic, while giving only minimal benefit in terms of lipid lowering. There is no real effect on HDL and triglyceride levels. From recent research it has become apparent that simvastatin and other statins inhibit the progression of atherosclerosis beyond their effects on LDL. A large number of explanations has been proposed, for example its inhibitory effect on macrophages in the atherosclerotic plaque lesions. Simvastatin was demonstrated to reduce older adults' chances of developing dementia by more than half. It was also found to reduce the risk of Parkinson's disease by 49%. Rationing Since its introduction, there has been a large debate surrounding the price for lipid-lowering treatment and its benefits on atherosclerosis. Although this has affected the other statins as well, simvastatin was the first statin drug to be used extensively in clinical practice. A number of large epidemiological studies were conducted to discover which patients would benefit most from statin drugs; most studies involve simvastatin as the study drug. The most influential studies were the Scandinavian Simvastatin Survival Study (4S) and the Heart protection study (HPS). It has now become apparent that patients with one or more risk factors for cardiovascular disease (such as diabetes mellitus, hypertension or a positive family history) can benefit from statins-even if they do not have substantially elevated cholesterol levels. Simvastatin was introduced in the late 1980s, and in many countries it is now available as a generic preparation. This has led to a decrease of the price of most statin drugs, and a reappraisal of the health economics of preventive statin treatment. In the UK, simvastatin (in a dose of 10 mg) has recently become available to purchase from pharmacies without prescription. Pharmacology All statins act by inhibiting HMG-CoA reductase, the rate-limiting enzyme of the HMG-CoA reductase pathway, the metabolic pathway responsible for the endogenous production of cholesterol. The drug is in the form of an inactive lactone that is hydrolized after ingestion to produce the active agent. It is a white, nonhygroscopic, crystalline powder that is practically insoluble in water, and freely soluble in chloroform, methanol and ethanol. Interactions Grapefruit contains the flavanones naringenin and bergamottin, which inhibit the liver cytochrome P450 3A4. This in turn slows metabolization of simvastatin and a large number of other drugs. Therefore, patients taking simvastatin should restrict their intake of grapefruit and grapefruit-containing products. Side effects Common side effects (>1% incidence) may include abdominal pain, diarrhea, indigestion, and a general feeling of weakness. Rare side effects include joint pain, memory loss, and muscle cramps. Marketing Simvastatin was initially marketed by Merck & Co under the trade name Zocor, but is now also available generically in most countries following the patent expiry. A combination of Simvastatin along with Ezetimibe is currently sold under the brand name Vytorin and is jointly marketed by Merck and Schering-Plough. The primary US patent for Zocor expired on June 23, 2006; Ranbaxy Laboratories (at the 80-mg strength) and Teva Pharmaceutical Industries through its Ivax Pharmaceuticals unit (at all other strengths) were given approval by the FDA to manufacture and sell simvastatin as a generic drug with 180-day exclusivity. Dr. Reddy's Laboratories also has a license from Merck & Co. to sell simvastatin as an authorized generic drug. Ezetimibe/simvastatin is a combination product to lower lipids and marketed as Vytorin. Sales Prior to losing U.S. patent protection, simvastatin was Merck & Co.’s largest selling drug and second largest selling cholesterol lowering drug in the world; it recorded 4.3 billion dollars of sales in 2005. Zocor had an original patent expiration date of January 2006 but was extended by the United States Food and Drug Administration (FDA) to expire on June 23, 2006. The FDA granted the patent extension after Merck & Co, Inc. submitted data from studies of the drug’s positive effect on children, a move typically used by drug companies to lengthen exclusivity. Ordinarily, Merck & Co. would have expected a sharp decrease in sales after the generic versions of simvastatin entered the market; however, Merck has slashed the price of Zocor dramatically in an effort to claim sales that would have otherwise gone to the generic versions. At least two major U.S. health insurers, UnitedHealthcare and WellPoint, are now offering Zocor to their members at generic copays. In addition, since Merck & Co. itself manufactures at least some versions of Dr. Reddy's authorized generic simvastatin. Merck & Co. is also poised to profit from the Dr. Reddy's version. An 80 mg, 30-count bottle of Dr. Reddy's simvastatin obtained July 6, 2006, states it is made by Merck Sharp & Dohme (Merck & Co.'s name outside the US to avoid conflicts with Merck KGaA) in the UK, just like 80 mg Zocor, and has a Merck & Co. logo on the bottom; except for omitting the "80" on one side, the tablets are visually identical to 80 mg Zocor, including "543" on the other side which is the key part of the National Drug Code for 80 mg Zocor. |
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