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Marketed under the trade name Zocor, it is a lipid-lowering drug.
It is used in conjunction with exercise, diet, and weight loss to lower high lipids (fats) levels.
Simvastatin is also used to reduce the risk of stroke, lower the risk of heart problems in people at high risk, and other heart complications in people with diabetes, coronary heart disease, or other risk factors. It is taken orally.
Serious side effects can include muscle breakdown, liver problems, and increased blood sugar levels. Common side effects include constipation , headaches, and nausea.
A lower dose may be necessary for people with kidney problems. There is evidence of harm to unborn babies when taken during pregnancy, and it should not be used by those who are breastfeeding.
It is in the statin class of drugs and works by decreasing the production of cholesterol in the liver.
Simvastatin was developed by Merck and entered medical use in 1992. On the World Health Organization’s Essential Drug List, it is the most effective and safest drug needed in a healthcare system.
It is available as a generic drug. The wholesale cost in the developing world is the US $ 0.01 to 0.12 per day as of 2014. In the United States, it costs between the US $ 0.50 and 1.00 per day. Simvastatin is made from the fungus Aspergillus terreus.
Medical uses
The main uses of simvastatin are to treat dyslipidemia and prevent atherosclerosis-related complications, such as stroke and heart attacks, in those at high risk. It is recommended that it be used to add to a low cholesterol diet.
In the Scandinavian simnedinatin survival study, a five-year randomized placebo-controlled clinical trial.
Simvastatin reduced overall mortality in people with existing cardiovascular disease and high low-density lipoprotein cholesterol by 30% and reduced cardiovascular mortality by 42%.
The risks of heart attack, stroke, or the need for a coronary artery bypass procedure were reduced by 37%, 28%, and 37%, respectively.
The Heart Protection Study evaluated the effects of simvastatin in people with risk factors, including existing cardiovascular disease, diabetes, or stroke, but who have relatively low low-density lipoprotein 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 delay the onset and progression of age-related macular degeneration (AMD).
Results from one trial showed that participants assigned to simvastatin were less likely (0.51 OR) to have age-related macular degeneration progression at three years compared to placebo, although the results were not significant.
Overall, the evidence is insufficient to conclude that simvastatin has an effect in delaying the onset and progression of age-related macular degeneration.
Contraindications
Simvastatin is contraindicated in pregnancy, lactation, and liver disease. Pregnancy should be avoided while on simvastatin due to potentially severe congenital disabilities.
Patients cannot breastfeed while taking simvastatin due to the possibility of altering the baby’s lipid metabolism.
High doses of simvastatin are also contraindicated with the widely used antihypertensive amlodipine.
A lower dose is also recommended in people taking calcium channel blockers, verapamil, and diltiazem, as well as those taking amiodarone.
Adverse effects
Common side effects (> 1% incidence) can include indigestion and eczema. Rare side effects include joint pain, memory loss, and muscle cramps.
Cholestatic hepatitis, liver cirrhosis, rhabdomyolysis (destruction of muscles and blockage of the renal system), and myositis have been reported in patients receiving the drug chronically. Severe allergic reactions to simvastatin are rare.
If the following signs of a severe allergic reaction appear, seek immediate medical attention: rash, hoarseness, itching/swelling, dizziness, or difficulty swallowing/breathing.
Stop using simvastatin and call your doctor at once if you have:
- Unexplained muscle pain, tenderness, or weakness.
- Confusion, memory problems.
- Fever, unusual tiredness, and dark-colored urine.
- Pain or burning when urinating.
- Swelling, weight gain, little or no urination.
- Increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, and weight loss.
- Nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, and jaundice (yellowing of the skin or eyes).
Less serious side effects may include:
- Headache.
- Joint pain, mild muscle pain.
- Constipation, stomach pain or indigestion, mild nausea.
- Mild skin rash.
- Trouble sleeping ( insomnia ).
- Cold symptoms such as stuffy nose, sneezing, and sore throat.
This is not a complete list of side effects, and others may occur. Call your doctor for medical information on side effects.
A DNA variant known as a single nucleotide polymorphism (SNP) can help predict people prone to developing myopathy when taking simvastatin.
A study that eventually included 32,000 patients concluded that carriers of one or two risk alleles of particular single nucleotide polymorphism, rs4149056, had a five- or 16-fold increased risk, respectively.
In 2012, the Clinical Pharmacogenetics Implementation Consortium published guidelines on using the rs4149056 genotype to guide the administration of simvastatin and updated the policies in 2014.
In March 2012, the Food and Drug Administration updated its guide for statin users to address reports of memory loss, liver damage, increased blood sugar, development of type 2 diabetes, and muscle injury.
On March 19, 2010, the Food and Drug Administration issued another statement regarding simvastatin. It increases the risk of muscle injury (myopathy) when taken in high doses or lower doses with other drugs.
In contrast to a lower dose, the higher dose rate causes muscle damage in 610 out of 10,000 people, which causes muscle damage in eight out of 10,000 people.
The Food and Drug Administration warning was re-released on June 8, 2011.
He suggested that ‘high dose simvastatin should only be used 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. Drug”.
Interactions
Simvastatin has significant interactions with grapefruit juice and other drugs, including some commonly used to treat cardiovascular disease.
These interactions are clinically crucial because raising simvastatin serum levels above those typically provided by the maximum recommended dose increases the risk of muscle damage, including the otherwise rare and life-threatening side effect of rhabdomyolysis.
Consuming large amounts of grapefruit juice increases serum simvastatin levels by up to three times, increasing the risk of side effects.
The Food and Drug Administration recommends that people taking statins avoid consuming more than one quart (946 ml) of grapefruit juice per day.
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 medications, fluconazole, itraconazole, or posaconazole; the antibiotics erythromycin, clarithromycin, or telithromycin; HIV protease inhibitors.
The antidepressant nefazodone, the cardiovascular drug gemfibrozil, the immunosuppressant cyclosporine, or danazol’s endometriosis drug.
Reduced maximum doses of simvastatin apply to patients taking other medications, including the cardiovascular medications verapamil, diltiazem, amiodarone, amlodipine, and ranolazine.
Many other drugs can interact with simvastatin. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medications to any healthcare provider who treats you.
Before taking simvastatin, tell your doctor if you have ever had liver or kidney disease, diabetes, or a thyroid disorder, if you are of Chinese descent, or if you drink more than two alcoholic beverages per day.
You should not take simvastatin if you are allergic to the drug, have liver disease, or are pregnant or breastfeedingbreastfeeding.
This condition is more likely to occur in older adults and people with kidney disease or poorly controlled hypothyroidism (underactive thyroid).
You are also more likely to develop this condition if you are of Chinese descent and take simvastatin in high doses while taking niacin medications (Advisor, Niaspan, Niacor, Simcor, Slo-Niacin, and others).
Your doctor may need to change your treatment plan if you use any of the following medications:
- Cyclosporine.
- Danazol.
- Gemfibrozil.
- Nefazodone.
- The antibiotics are clarithromycin, erythromycin, and telithromycin.
- Antifungal medications; itraconazole, ketoconazole, and posaconazole.
- Drugs against hepatitis C; boceprevir and telaprevir.
- HIV / AIDS drugs; atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, and tipranavir.
Before you start taking simvastatin, tell your doctor if you are already using any of these other medications:
- Amiodarone
- Diltiazem.
- Amlodipine.
- Ranolazine.
- Verapamil.
To make sure simvastatin is safe for you, tell your doctor if you have:
- History of liver disease.
- History of kidney disease.
- Diabetes.
- A thyroid disorder.
- If you drink more than two alcoholic drinks daily.
Not all possible interactions are listed here. Tell your doctor about all your medications and any you start or stop using during treatment with simvastatin, especially:
- Colchicine.
- Digoxin.
- A blood thinner such as warfarin or coumadin.
- Fenofibric acid or fenofibrate.
- Antimycotic drugs such as fluconazole or voriconazole.
Medicines that weaken your immune systems, such as steroids, cancer medicines, or medicines used to prevent organ transplant rejection, such as sirolimus or tacrolimus,
Any other ‘statin’ medicine such as atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, or another simvastatin medicine.
How should I take simvastatin?
You may need to take simvastatin long-term to treat high cholesterol. Follow your diet, medication, and exercise routines continuously. Avoid eating foods that are high in fat or cholesterol.
Simvastatin won’t be as effective at lowering cholesterol if you don’t follow a cholesterol-lowering diet plan. If you have questions about the medicines you are taking, ask your doctor, nurse, or pharmacist.
Pharmacology
All statins work by inhibiting 3-hydroxy-3-methylglutaryl (HMG) coenzyme A reductase. HMG-CoA reductase, the rate-limiting enzyme of the HMG-CoA reductase pathway, is the metabolic pathway responsible for endogenous cholesterol production.
Statins are more effective than other lipid-regulating drugs in reducing the concentration of low-density lipoprotein cholesterol. Still, they are less effective than fibrates in lowering the concentration of triglycerides.
However, statins reduce cardiovascular disease events and total mortality regardless of the initial cholesterol level.
This is substantial evidence that statins work other than lowering cholesterol (called pleiotropic effects).
The drug is in the form of an inactive lactone that hydrolyzes after ingestion to produce the active agent. It is a white, non-hygroscopic, crystalline powder that is practically insoluble in water and soluble in chloroform, methanol, and ethanol.
Simvastatin is an effective lipid-lowering drug that can lower low-density lipoprotein (LDL) levels by up to 50%.
Simvastatin has been shown to interact with the lipid-lowering transcription factor PPAR-alpha and that the interaction could control the neurotrophic action of the drug.
History
The development of simvastatin was closely related to lovastatin. Biochemist Jesse Huff and his colleagues at Merck began investigating cholesterol biosynthesis in the early 1950s.
In 1956, mevalonic acid was isolated from a yeast extract by Karl Folkers, Carl Hoffman, and others at Merck. Huff and their collaborators confirmed that mevalonic acid was an intermediate in cholesterol biosynthesis.
In 1959, researchers at the Max Planck Institute discovered the enzyme HMG-CoA reductase (a significant contributor to internal cholesterol production). This discovery encouraged scientists worldwide to find an effective inhibitor of this enzyme.
In 1976, Akira Endo isolated the first inhibitor, mevastatin, from the fungus Penicillium citrinium while working at Daiichi Sankyo in Japan. In 1979, Hoffman and his 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, designated MK-733 (later to be called simvastatin).
In 1994, the publication of the Scandinavian Simvastatin Survival Study (4S) provided the first unequivocal evidence that lowering LDL cholesterol through statin treatment reduces cardiovascular events and overall mortality.
Four hundred forty-four people with CHD 5.5 to 8.0 mmol / L were randomized to treatment with simvastatin or placebo and followed for five years.
Compared with 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 coronary events—revascularization procedures.
Society and culture
Economic Sciences
Simvastatin was introduced in the late 1980s and has been available as a generic preparation in many countries since 2006. This has led to a decrease in the price of most statin drugs and a reassessment of the health economics of preventive statin treatment.
In the UK in 2008, the typical NHS cost per patient for simvastatin was around £ 1.50 per month. (40 mg/day cost UK National Health Service £ 1.37 / month in 2012)
Before losing US patent protection, simvastatin was Merck & Co.’s top-selling drug and the second-best-selling cholesterol-lowering drug in the world. In 2005, it posted sales of US $ 3.1 billion in the US and the US $ 4.4 billion worldwide.
Zocor had an original patent expiration date of January 2006, but it was extended by the United States Patent Trademark Office to expire on June 23, 2006.
The Patent Trademark Office granted the patent extension after Merck submitted data from effect studies on children. In the UK, the patent for simvastatin expired in 2004.
In the UK, simvastatin is the most widely prescribed drug in the community, with 39.9 million items dispensed in 2013. This compares with 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.
Marketing
Simvastatin was initially marketed by Merck & Co under the trade name Zocor but is available generically in most countries after the patent’s expiration. A combination of simvastatin and ezetimibe is sold under the brand name Vytorin and is jointly marketed by Merck and Schering-Plow.
Brands include Zocor, and Zocor Heart Pro, marketed by the pharmaceutical company Merck & Co.
Available in Thailand under Bestatin’s brand name, manufactured by Berlin Pharmaceutical Industry Co Ltd and others. The main US patent
For Zocor expired on June 23, 2006. Ranbaxy Laboratories (with a concentration of 80 mg).
Through its Ivax Pharmaceuticals unit (in all other strengths), Teva Pharmaceutical Industries received approval from the Food and Drug Administration to manufacture and sell simvastatin as a generic drug with 180-day exclusivity.
Dr. Reddy’s Laboratories is also licensed by Merck & Co. to sell simvastatin as an approved generic drug.
Every effort has been made to ensure that the information provided by Cerner Multum, Inc. (‘Multum’) is accurate, current, and complete, but no warranty is made in this regard. The drug information included here may be time-sensitive.
Multiple information has been compiled for healthcare professionals and consumers in the United States. Therefore, Multum does not guarantee that uses outside the United States are appropriate unless expressly stated otherwise.
Multum’s drug information does not endorse, diagnose patients, or recommend therapy.
