SimvastatinClinical dataPronunciation Trade namesZocor, otherAHFS/Drugs.comMonographMedlinePlusa692030License dataPregnancycategory
O=C(O[C@@H]1[C@H]3C(=C/[C@H](C)C1)C=C/[C@@H]([C@@H]3CC[C@H]2OC(=O)C[C@H](O)C2)C)C(C)(C)CC
Simvastatin, marketed under the trade name Zocor among others, is a lipid-lowering medication.[1] It is used along with exercise, diet, and weight loss to decrease elevated lipid (fat) levels.[1] It is also used to decrease the risk of heart problems in those at high risk.[1] It is taken by mouth.[1]
Serious side effects may include muscle breakdown, liver problems, and increased blood sugar levels.[1] Common side effects include constipation, headaches, and nausea.[1] A lower dose may be needed in people with kidney problems.[1] There is evidence of harm to unborn babies when taken during pregnancy[1][2] and it should not be used by those who are breastfeeding.[1] It is in the statin class of medications and works by decreasing the manufacture of cholesterol by the liver.[1]
Simvastatin was developed by Merck and came into medical use in 1992.[3] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[4] It is available as a generic medication.[1] The wholesale cost in the developing world is US$0.01 to 0.12 per day as of 2014[update].[5] In the United States it costs between US$0.50 and 1.00 per day.[1] Simvastatin is made from the fungus Aspergillus terreus.[3]
The primary uses of simvastatin are to treat dyslipidemia and to prevent atherosclerosis-related complications such as stroke and heart attacks in those who are at high risk.[1] It is recommended to be used as an addition to a low-cholesterol diet.[1]
In the Scandinavian Simvastatin Survival Study (a placebo-controlled, randomized clinical trial of five years' duration), simvastatin reduced overall mortality in people with existing cardiovascular disease and high LDL cholesterol by 30% and reduced cardiovascular mortality by 42%. The risks of heart attack, stroke, or needing a coronary revascularization procedure were reduced by 37%, 28%, and 37%, respectively.[6]
The Heart Protection Study evaluated the effects of simvastatin in people with risk factors including existing cardiovascular disease, diabetes, or stroke, but having 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 receiving simvastatin experienced 38% fewer nonfatal heart attacks and 25% fewer strokes.[7]
Simvastatin has been used to explore whether statins have an effect on delaying on the onset and progression of age-related macular degeneration (AMD).[8] Results from one trial showed participants assigned to simvastatin had lower odds (0.51 OR) of having AMD progression at three years compared to those assigned to placebo, though the results were not significant.[9] Overall, evidence is insufficient to conclude that simvastatin has an effect in delaying the onset and progression of AMD.[8]
Simvastatin is contraindicated with pregnancy, breastfeeding, and liver disease.[10] Pregnancy must be avoided while on simvastatin due to potentially severe birth defects. Patients cannot breastfeed while on simvastatin due to potentially disrupting the infant's lipid metabolism.[11] High doses of simvastatin are also contraindicated with the widely used antihypertensive amlodipine.[12] A lower dose is also recommended in people taking the calcium channel blockers, verapamil and diltiazem, as well as those taking amiodarone.[13]
Common side effects (>1% incidence) may include indigestion and eczema. Rare side effects include joint pain, memory loss, and muscle cramps.[14] Cholestatic hepatitis, hepatic cirrhosis, rhabdomyolysis (destruction of muscles and blockade of renal system), and myositis have been reported in patients receiving the drug chronically.[15] Serious allergic reactions to simvastatin are rare.[10] If the following signs of a serious allergic reaction occur, seek medical attention immediately: rash, hoarsness itching/swelling, dizziness, or difficulty swallowing/breathing.[10]
A type of DNA variant known as a single nucleotide polymorphism (SNP) may help predict individuals prone to developing myopathy when taking simvastatin; a study ultimately including 32,000 patients concluded the carriers of one or two risk alleles of a particular SNP, rs4149056,[16] were at a five-fold or 16-fold increased risk, respectively.[17] In 2012, the Clinical Pharmacogenetics Implementation Consortium has released guidelines regarding the use of rs4149056 genotype in guiding dosing of simvastatin[18] and updated the guideline in 2014.[19]
In March 2012, the FDA updated its guidance for statin users to address reports of memory loss, liver damage, increased blood sugar, development of type 2 diabetes, and muscle injury.[20] The new guidance indicates:
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 lower doses in combination with other drugs.[21] The highest dose rate causes muscle damage in 610 of every 10,000 people in contrast to a lower dose, which causes muscle damage in eight of 10,000 people.[22] The FDA warning, released again on June 8, 2011, suggested that high-dose "simvastatin should be used only in patients who have been taking this dose for 12 months or more without evidence of muscle injury" and that it "should not be started in new patients, including patients already taking lower doses of the drug."[23]
Simvastatin has important interactions with grapefruit juice and other drugs, including some that are commonly used for the treatment of cardiovascular disease. These interactions are clinically important because increasing simvastatin serum levels above those normally provided by the maximum recommended dose increases the risk of muscle damage, including the otherwise rare and potentially fatal side effect of rhabdomyolysis.[24]
Consuming large amounts of grapefruit juice increases serum levels of simvastatin by up to three-fold, increasing the risk of side effects.[25][26][27][28] The FDA recommends that people taking statins should avoid consuming more than a quart (946 ml) of grapefruit juice per day.[24]
Simvastatin also interacts with other drugs, including some used to treat cardiovascular problems. It should not be taken by people who are also taking the antifungal drugs fluconazole, itraconazole, or posaconazole; the antibiotics erythromycin, clarithromycin, or telithromycin; HIV protease inhibitors; the antidepressant nefazodone; the cardiovascular drug gemfibrozil; the immunosuppressant ciclosporin, or the endometriosis drug danazol. Reduced maximum doses of simvastatin apply for patients taking certain other drugs, including the cardiovascular drugs verapamil, diltiazem, amiodarone, amlodipine, and ranolazine.[24][29]
All statins act by inhibiting 3-hydroxy-3-methylglutaryl (HMG) coenzyme A reductase. HMG-CoA reductase, the rate-limiting enzyme of the HMG-CoA reductase pathway, the metabolic pathway responsible for the endogenous production of cholesterol. Statins are more effective than other lipid-regulating drugs at lowering LDL-cholesterol concentration, but they are less effective than the fibrates in reducing triglyceride concentration. However, statins reduce cardiovascular disease events and total mortality irrespective of the initial cholesterol concentration. This is a major piece of evidence that statins work in another way than the lowering of cholesterol (called pleiotropic effects).[30]
The drug is in the form of an inactive lactone that is hydrolyzed 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.
Simvastatin is an effective serum lipid-lowering drug that can decrease low density lipoprotein (LDL) levels by up to 50%.[citation needed] Simvastatin had been shown to interact with lipid-lowering transcription factor PPAR-alpha [31] and that interaction might control the neurotrophic action of the drug.
The development of simvastatin was closely linked with lovastatin. Biochemist Jesse Huff and his colleagues at Merck began researching the biosynthesis of cholesterol in the early 1950s.[32] In 1956, mevalonic acid was isolated from a yeast extract by Karl Folkers, Carl Hoffman, and others at Merck, while Huff and his associates confirmed that mevalonic acid was an intermediate in cholesterol biosynthesis. In 1959, the HMG-CoA reductase enzyme (a major contributor of internal cholesterol production) was discovered by researchers at the Max Planck Institute. This discovery encouraged scientists worldwide to find an effective inhibitor of this enzyme.[citation needed]
By 1976, Akira Endo had isolated the first inhibitor, mevastatin, from the fungus Penicillium citrinium while working at Daiichi Sankyo in Japan.[33] In 1979, Hoffman and colleagues isolated lovastatin from a strain of the fungus Aspergillus terreus. While developing and researching lovastatin, Merck scientists synthetically derived a more potent HMG-CoA reductase inhibitor from a fermentation product of A. terreus, which was designated MK-733 (later to be named simvastatin).[34]
In 1994, publication of the results of the Scandinavian Simvastatin Survival Study (4S) provided the first unequivocal evidence that lowering LDL cholesterol via statin treatment reduces cardiovascular events and overall mortality. A total of 4,444 people with coronary heart disease 5.5 to 8.0mmol/L were randomized to simvastatin treatment or placebo and followed for an average of 5 years. Compared to the placebo group, those treated with simvastatin experienced a 30% decrease in overall mortality, a 42% reduction in coronary death, a 34% reduction in major coronary events, and a 37% reduction in revascularization procedures.[35]
Simvastatin was introduced in the late 1980s, and since 2006 in many countries, it is 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 in 2008, the typical per-patient cost to the NHS of simvastatin was about 1.50 per month.[36] (40mg/day costs UK NHS 1.37/month in 2012[37])
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. In 2005, recorded US$3.1billion of sales in the US and US$4.4billion worldwide.[38]
Zocor had an original patent expiry date of January 2006, but was extended by the United States Patent Trademark Office (PTO) to expire on June 23, 2006.[citation needed] The PTO granted the patent extension after Merck submitted data from studies of the drugs positive effect on children. In the UK, the patent for simvastatin had expired by 2004.[citation needed]
In the UK, simvastatin is the most prescribed medication in the community, with 39.9 million items dispensed in 2013. This compares to 30.9 million items for aspirin, and 27.7 million for levothyroxine sodium, the second- and third-most prescribed drugs in the UK in 2013.[39]
Simvastatin was initially marketed by Merck & Co under the trade name Zocor, but is available generically in most countries following the patent expiry. A combination of simvastatin along with ezetimibe is sold under the brand name Vytorin and is jointly marketed by Merck and Schering-Plough.
Brand names include Zocor, Zocor Heart Pro, marketed by the pharmaceutical company Merck & 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 brand Bestatin manufactured by Berlin Pharmaceutical Industry Co Ltd and others.[citation needed]
The primary U.S. patent for Zocor expired on June 23, 2006.[citation needed] 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.[citation needed]
Read the rest here:
Simvastatin - Wikipedia
- Cerebral Palsy: Diagnosis - May 7th, 2011 [May 7th, 2011]
- Cerebral palsy treatment NeuWellness - May 14th, 2011 [May 14th, 2011]
- cerebral palsy treatment in india-indian cerebral palsy video 1 - May 20th, 2011 [May 20th, 2011]
- CP Cerebral Palsy Acupuncture Treatment Research. www.thetole.org - May 24th, 2011 [May 24th, 2011]
- cerebral palsy treatment in india/dr vipul shah/ indian cerebral palsy - June 9th, 2011 [June 9th, 2011]
- cerebral palsy treatment in india/indian cerebral palsy/dr vipul shah/follow up - June 23rd, 2011 [June 23rd, 2011]
- TheraSuit treatment for Cerebral Palsy - July 3rd, 2011 [July 3rd, 2011]
- Stem cell treatment for Cerebral Palsy-Jerica Cole's post interview.avi - July 15th, 2011 [July 15th, 2011]
- Cerebral Palsy Treatment.... Hindi - August 19th, 2011 [August 19th, 2011]
- Stem Cell Treatment for Cerebral Palsy (Periventricular Leukomalacia) - August 21st, 2011 [August 21st, 2011]
- Stem Cell Treatment for Cerebral Palsy at the XCell-Center in Germany - August 25th, 2011 [August 25th, 2011]
- cerebral palsy treatment,lilou,essentis,therasuit,banana,spider,nazarov,guez - August 29th, 2011 [August 29th, 2011]
- cerebral palsy treatment,helena,essentis,therasuit,guez,spider,nazarov,guez - September 30th, 2011 [September 30th, 2011]
- walking before training lokomat for cerebral palsy treatment - September 30th, 2011 [September 30th, 2011]
- TheraSuit Therapy for Cerebral Palsy - Case 1 - October 2nd, 2011 [October 2nd, 2011]
- Cerebral palsy patient Atillia before stem cell treatment 2.wmv - October 10th, 2011 [October 10th, 2011]
- Stem cell treatment for Cerebral Palsy-Jerica Cole's pre interview.avi - October 11th, 2011 [October 11th, 2011]
- Stem Cell Treatment - Cerebral Palsy (2) - Video - October 16th, 2011 [October 16th, 2011]
- magic treatment for cerebral palsy -indian cerebral palsy treatment in india/delhi - Video - October 18th, 2011 [October 18th, 2011]
- Cerebral palsy patient Atillia after stem cell treatment 1.wmv - Video - October 19th, 2011 [October 19th, 2011]
- Cerebral Palsy: A new treatment: Part 1 - Video - October 21st, 2011 [October 21st, 2011]
- Cerebral Palsy Hyperbaric treatment in Margate Florida 954-975-3563 - Video - October 22nd, 2011 [October 22nd, 2011]
- Cerebral palsy patient Gabor after stem cell treatment 3.1.wmv - Video - October 29th, 2011 [October 29th, 2011]
- Stem Cell Treatment for Cerebral Palsy - Video - October 30th, 2011 [October 30th, 2011]
- Brian's Story: Dr. Huo's miraculous acupuncture treatment of Cerebral Palsy - Video - October 30th, 2011 [October 30th, 2011]
- Hyperbaric Oxygen Therapy Treatment for Cerebral Palsy - Video - November 1st, 2011 [November 1st, 2011]
- After Stem Cell Transplant treatment for Cerebral Palsy - Video - November 2nd, 2011 [November 2nd, 2011]
- indian cerebral palsy treatment-dr vipul shah - Video - November 6th, 2011 [November 6th, 2011]
- Stem Cell Therapy for Cerebral Palsy - Video - November 10th, 2011 [November 10th, 2011]
- Cerebral Palsy(CP) Scientific Treatment Research Center - Video - November 10th, 2011 [November 10th, 2011]
- Cerebral Palsy Treatment - November 17th, 2011 [November 17th, 2011]
- Stem Cells: Treatment for Cerebral Palsy - Video - December 10th, 2011 [December 10th, 2011]
- Stem Cell Therapy - Cerebral Palsy Treatment || Holly Catalano Update - Video - December 29th, 2011 [December 29th, 2011]
- Lasertherapy Bular - Treatment of Infantile Cerebral Palsy - Video - January 4th, 2012 [January 4th, 2012]
- Cerebral palsy patient Bianca after stem cell treatment 3.wmv - Video - January 4th, 2012 [January 4th, 2012]
- Cerebral Palsy Treatment by Dr.Babu Sudheendra Nath - Video - January 31st, 2012 [January 31st, 2012]
- The Methodist Hospital in Houston Is First to Offer New Device to Improve Walking - February 1st, 2012 [February 1st, 2012]
- Baby Logan inspires family to help - February 14th, 2012 [February 14th, 2012]
- Santi KM Bhagat: The 8 Million That Health Care Reform Forgot - February 14th, 2012 [February 14th, 2012]
- Ben's Bells: Patient grateful for Brownies' efforts - February 19th, 2012 [February 19th, 2012]
- Family’s appeal to improve care for disabled Jack, 3 - February 20th, 2012 [February 20th, 2012]
- Families, hospitals fighting Medicaid cuts - February 20th, 2012 [February 20th, 2012]
- Barrow family’s appeal to improve care for disabled Jack, 3 - February 20th, 2012 [February 20th, 2012]
- Earnings Beat for Acorda - February 21st, 2012 [February 21st, 2012]
- Dance to support Shriners Hospital for Children - February 25th, 2012 [February 25th, 2012]
- US trip holds hope for city boy - February 28th, 2012 [February 28th, 2012]
- Santanu Mitra - February 28th, 2012 [February 28th, 2012]
- City hospital to offer walking op - February 28th, 2012 [February 28th, 2012]
- CBR's Newborn Possibilities Program Provides Cord Blood Banking at No Cost to Families with an Identified Medical Need - February 29th, 2012 [February 29th, 2012]
- Charity golfers to the fore - February 29th, 2012 [February 29th, 2012]
- Assistive Mobility Devices Designed by Mobility Research Now Offered by Rehabmart.com - March 2nd, 2012 [March 2nd, 2012]
- Help to give Aiden, 2, chance of better life - March 4th, 2012 [March 4th, 2012]
- Conman Neil Jackson jailed for six years after false sickness claims for son - March 4th, 2012 [March 4th, 2012]
- Tesco manager conned £60k out of staff for son's 'fatal illness' and spent it on holidays - March 6th, 2012 [March 6th, 2012]
- Tesco manager conned £60,000 out of staff for son¿s ¿fatal illness¿ and spent the money on holidays to Hawaii and Las ... - March 6th, 2012 [March 6th, 2012]
- Ontario At The Centre Of World-Leading Brain Research - March 6th, 2012 [March 6th, 2012]
- R5.5m claim after baby born with cerebral palsy - March 6th, 2012 [March 6th, 2012]
- Uncertainty over NHS reforms threatens future of world leading cerebal palsy centre - March 6th, 2012 [March 6th, 2012]
- Birth Injuries from Medical Malpractice Can Create a Lifetime of Financial and Emotional Challenges for Victims and ... - March 7th, 2012 [March 7th, 2012]
- Ontario brains put their heads together - March 7th, 2012 [March 7th, 2012]
- ‘PediaSuit’ helps cerebral palsy patient walk - March 9th, 2012 [March 9th, 2012]
- Charity Caudwell Children donates wheelchair to Norwich youngster - March 10th, 2012 [March 10th, 2012]
- Elgin Easter Seals gets more space, bilingual programs - March 11th, 2012 [March 11th, 2012]
- A war on brain illness should be declared - March 12th, 2012 [March 12th, 2012]
- More children now living with 'life-limiting' conditions - March 12th, 2012 [March 12th, 2012]
- Assessing innovative intervention for children with cerebral palsy - March 15th, 2012 [March 15th, 2012]
- Cerebral Palsy In Children - Innovative Intervention Evaluated - March 15th, 2012 [March 15th, 2012]
- Cerebral palsy hindering 4-year-oldâs movement - March 17th, 2012 [March 17th, 2012]
- West Fargo boy with cerebral palsy can now walk without crutches; parents credit stem cell therapy - March 19th, 2012 [March 19th, 2012]
- Cerebral palsy research brings hope to new mums - March 21st, 2012 [March 21st, 2012]
- Center offers hyperbaric treatment - March 21st, 2012 [March 21st, 2012]
- $100-million Children’s Treatment Centre to be built in lower city - March 22nd, 2012 [March 22nd, 2012]
- White Lodge Centre marks 50 years in 2012 - March 22nd, 2012 [March 22nd, 2012]
- Telethon Delivers Life Changing Services - March 23rd, 2012 [March 23rd, 2012]
- Teachers allegedly call special-needs kid 'disgusting' - March 31st, 2012 [March 31st, 2012]
- Cerebral palsy drug may offer hope for treatment - April 20th, 2012 [April 20th, 2012]
- Prevention of cerebral palsy - April 20th, 2012 [April 20th, 2012]
- Study gives new hope on cerebral palsy - April 20th, 2012 [April 20th, 2012]
- Prrvention of cerebral palsy - April 20th, 2012 [April 20th, 2012]
- PRB at Wayne State/DMC discover window of opportunity to prevent cerebral palsy - April 20th, 2012 [April 20th, 2012]