Simvastatin , marketed under the trade name Zocor , among others, is a lipid-lowering drug. It is used in conjunction with exercise, diet, and weight loss to lower high lipid (fat) levels. It is also used to reduce the risk of heart problems in those at high risk. It was taken by mouth.
Serious side effects may include muscle damage, liver problems, and elevated blood sugar levels. Common side effects include constipation, headache, and nausea. Lower doses may be needed in people with kidney problems. There is evidence of harm to unborn babies when taken during pregnancy and should not be used by those who are breastfeeding. This drug is in the statin drug class and works by lowering cholesterol production by the liver.
Simvastatin was developed by Merck and began to be used in 1992. It is on the World Health Organization's Essential Drug List, the most effective and safe medication needed in the health system. It is available as a generic drug. Wholesale costs in developing countries are US $ 0.01 to 0.12 per day in 2014. In the United States it costs between US $ 0.50 and 1.00 per day. Simvastatin is made of mushrooms Aspergillus terreus .
Video Simvastatin
Medical use
The primary use of simvastatin is to treat dyslipidemia and to prevent atherosclerosis-related complications such as stroke and heart attack in those at high risk. It is recommended to be used in addition to low cholesterol diet.
In the Scandinavian Simvastatin Survival Study, simvastatin reduced overall mortality in people with existing cardiovascular disease and high LDL cholesterol by 30% and reduced cardiovascular mortality by 42%. The risk of heart attack, stroke, or require coronary revascularization procedures was reduced by 37%, 28%, and 37%, respectively.
The Heart Protection Study evaluates the effects of simvastatin in people with risk factors including existing cardiovascular disease, diabetes, or stroke, but has relatively low LDL cholesterol. In this trial, which lasted 5.4 years, overall mortality was reduced by 13% and cardiovascular mortality was reduced by 18%. People who received simvastatin experienced 38% fewer non-fatal heart attacks and 25% fewer strokes.
Simvastatin has been used to explore whether statins have an effect on delay onset and progression of age-related macular degeneration (AMD). Results from one trial showed participants assigned to simvastatin had a lower chance (0.51 OR) had an AMD development at three years compared with those assigned to placebo, although the results were not significant. Overall, evidence is insufficient to conclude that simvastatin has the effect of delaying the onset and development of AMD.
Maps Simvastatin
Contraindications
Simvastatin is contraindicated with pregnancy, lactation, and liver disease. Pregnancy should be avoided at simvastatin due to potentially severe birth defects. Patients can not breastfeed during simvastatin because of the potential to interfere with baby's lipid metabolism. High doses of simvastatin are also contraindicated with widely used antihypertensive amlodipine. Lower doses are also recommended in people who use calcium channel blockers, verapamil and diltiazem, as well as those who consume amiodarone.
Adverse effects
Common side effects (& gt; 1% incidence) may include indigestion and eczema. Rare side effects include joint pain, memory loss, and muscle cramps. Cholestatic hepatitis, liver cirrhosis, rhabdomyolysis (muscle destruction and kidney system blockade), and myositis have been reported in patients receiving chronic drugs. Serious allergic reactions to simvastatin are rare. If the following signs of a serious allergic reaction occur, seek immediate medical attention: rash, hives/swelling, dizziness, or difficulty swallowing/breathing.
A type of DNA variant known as single nucleotide polymorphism (SNP) can help predict susceptible individuals to develop myopathy when taking simvastatin; a study that eventually included 32,000 patients concluded that carriers of one or two risk alleles of a particular SNP, rs4149056, each had a five-fold increase or 16-fold increase. In 2012, the Clinical Pharmacogenetics Implementation Consortium has released guidelines on the use of genotype rs4149056 in guiding the simvastatin dosage and updating the guidelines by 2014.
In March 2012, the FDA updated its guidelines for statin users to address reports of memory loss, liver damage, increased blood sugar, the development of type 2 diabetes, and muscle injury. The new guide shows:
- The FDA has found that liver injury associated with statin use is rare but can occur.
- Reports about memory loss, forgetfulness, and confusion include all statin products and all age groups. The FDA says the experience is rare, but those affected often report feeling "blurred" or unfocused in their thinking. Increased risk of elevated blood sugar and the development of type 2 diabetes have been reported with statin use.
- Some drugs interact with statins in a way that increases the risk of muscle injury called myopathy, characterized by unexplained muscle weakness or pain.
On March 19, 2010, the FDA issued another statement regarding simvastatin, saying it increases the risk of muscle injury (myopathy) when taken at high doses or at low doses in combination with other drugs. The highest dose rate causes muscle damage in 610 of every 10,000 different people with lower doses, which causes muscle damage in eight out of 10,000 people. The FDA warning, released again on June 8, 2011, suggested that high doses of "simvastatin should be used only in patients who have taken this dose for 12 months or more without evidence of muscle injury" and that it "should not be initiated in new patients, already taking lower doses of the drug. "
Interactions
Simvastatin has important interactions with orange juice and other drugs, including some commonly used for the treatment of cardiovascular diseases. This interaction is clinically important because increasing the serum levels of simvastatin above which are usually provided by the recommended maximum dose increases the risk of muscle damage, including rare and potentially fatal side effects of rhabdomyolysis.
Consuming grapefruit juice in large amounts increases serum simvastatin levels up to threefold, increasing the risk of side effects. The FDA recommends that people taking statins should avoid consuming more than one liter (946 ml) of orange juice daily.
Simvastatin also interacts with other drugs, including some used to treat cardiovascular problems. It should not be taken by people who also take the antifungals of fluconazole, itraconazole, or posaconazole; antibiotic erythromycin, clarithromycin, or telithromycin; HIV protease inhibitor; nefazodon antidepressants; gemfibrozil cardiovascular drugs; immunosuppressant ciclosporin, or drug danazol endometriosis. Reducing the maximum dose of simvastatin applies to patients taking certain other medications, including verapamil cardiovascular drugs, diltiazem, amiodarone, amlodipine, and ranolazine.
Pharmacology
All statins act by inhibiting 3-hydroxy-3-methylglutaryl (HMG) coenzyme A reductase. HMG-CoA reductase, enzyme limiting rate of HMG-CoA reductase pathway, the metabolic pathway responsible for the production of endogenous cholesterol. Statins are more effective than other lipid regulators on decreasing LDL cholesterol concentrations, but they are less effective than fibrates in reducing triglyceride concentrations. However, statins reduce the incidence of cardiovascular disease and total mortality regardless of initial cholesterol concentration. This is the main evidence that statins work in other ways than lowering cholesterol (called pleiotropic effects).
The drug is in the form of an inactive lactone which is hydrolyzed after consumption to produce the active ingredient. It is a white, nonhygroscopic crystalline powder, which is practically insoluble in water, and is soluble in chloroform, methanol, and ethanol.
Simvastatin is an effective serum lipid-lowering drug that can reduce low-density lipoprotein (LDL) levels by up to 50%. Simvastatin has been shown to interact with lipar-alpha lipid-lowering transcription factors and interactions that may control drug neurotrophic action.
History
The development of simvastatin is closely related to lovastatin. Biochemist Jesse Huff and his colleagues at Merck began researching cholesterol biosynthesis in the early 1950s. In 1956, mevalonic acid was isolated from yeast extract by Karl Folkers, Carl Hoffman, and others at Merck, while Huff and his colleagues confirmed that mevalonic acid is intermediate in cholesterol biosynthesis. In 1959, the enzyme HMG-CoA reductase (major contributor to the production of internal cholesterol) was discovered by researchers at the Max Planck Institute. This discovery encourages scientists around the world to find effective inhibitors of this enzyme.
In 1976, Akira Endo had isolated the first inhibitor, mevastatin, from the Penicillium citrinium fungus while working at Daiichi Sankyo in Japan. In 1979, Hoffman and his colleagues isolated lovastatin from the fungal strain of Aspergillus terreus . When developing and researching lovastatin, Merck scientists synthetically obtained a stronger HMG-CoA reductase inhibitor from the fermented product of A. terreus , designated MK-733 (later named simvastatin).
In 1994, the Scandinavian publication of the Simvastatin Survival Study (4S) provided the first firm evidence that lowering LDL cholesterol through statin treatment reduced overall cardiovascular and mortality events. A total of 4,444 people with coronary heart disease 5.5 to 8.0 mmol/L were randomized to simvastatin or placebo treatment and followed for an average of 5 years. Compared with the placebo group, those treated with simvastatin experienced a 30% reduction in overall mortality, a 42% decrease in coronary mortality, a 34% decrease in major coronary events, and a 37% reduction in revascularization procedures.
Society and culture
Economy
Simvastatin was introduced in the late 1980s, and since 2006 in many countries, it is available as a general preparation. This has led to a decline in prices of most statin drugs, and a reassessment of preventive health care static health care. In the UK in 2008, the cost per patient is typical for the NHS of simvastatin around Ã,  £ 1.50 per month. (40Ã, mg/day cost UK NHS Ã,  £ 1.37/month in 2012)
Before losing the U.S. patent protection, simvastatin is Merck & amp; The best-selling Co drug and the second largest cholesterol-lowering drug in the world. In 2005, it recorded US $ 3.1 billion in sales in the US and US $ 4.4 billion worldwide.
Zocor had the original patent expiry date of January 2006, but was renewed by the United States Trademark Patent Office (PTO) to expire on June 23, 2006. PTO granted patent extension after Merck sent data from studies of the positive effects of the drug on children. In the UK, the patent for simvastatin has expired in 2004.
In the UK, simvastatin is the most prescribed drug in the community, with 39.9 million items distributed in 2013. This compares to 30.9 million items for aspirin, and 27.7 million for levothyroxine sodium, the second most prescribed drug English. in 2013.
Marketing
Simvastatin was originally marketed by Merck & amp; Co under the trade name Zocor, but is generally available in most countries after the expiration of the patent. The simvastatin combination together with ezetimibe is sold under the trademark Vytorin and marketed jointly by Merck and Schering-Plow.
The brand names include Zocor, Zocor Heart Pro, marketed by Merck & amp; Co, Simlup, Simvotin, Simcard [India], Denan (Germany), Liponorm, Sinvacor, Sivastin (Italy), Lipovas (Japan), Lodales (France), Zocord (Austria and Sweden), Zimstat, Simvahexal (Australia), Lipex (Australia and New Zealand), Simvastatin-Teva, Simvacor, Simvaxon, Simovil (Israel), available in Thailand under the Bestatin brand produced by Berlin Pharmaceutical Industry Co Ltd and others.
The main US patent for Zocor ended on June 23, 2006. The Ranbaxy laboratory (at 80-mg strength) and Teva Pharmaceutical Industries through the Ivax Pharmaceutical unit (in all other powers) were given approval by the FDA to produce and sell simvastatin as a generic drug with 180 days exclusivity. Dr. Lab. Reddy also has a license from Merck & amp; Co. sells simvastatin as an official generic drug.
See also
- List of drugs affected by grapefruit
References
External links
- Simvastatin RxList.com
- US. National Library of Medicine: Drug Information Portal - Simvastatin
- "Zocor Prescribing Information". Merck & amp; Co.
Source of the article : Wikipedia
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