Simvastatin, marketed under the trade name Zocor among others, is a lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid (fat) levels. It is also used to decrease the risk of heart problems in those at high risk. It is taken by mouth. Serious side effects may include muscle breakdown, liver problems, and increased blood sugar levels. Common side effects include constipation, headaches, and nausea. A lower dose may be needed in 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 medications and works by decreasing the manufacture of cholesterol by the liver. Simvastatin was developed by Merck and came into medical use in 1992. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication. The wholesale cost in the developing world is 0.01 to 0.12 USD per day . In the United States it costs between 0.50 and 1.00 USD per day. Simvastatin is made from the fungus Aspergillus terreus.
Medical usesThe 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. It is recommended to be used as an addition to a low cholesterol diet. In the Scandinavian Simvastatin Survival Study (a placebo-controlled, randomized clinical trial of 5 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. 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 non-fatal heart attacks and 25% fewer strokes. Simvastatin has been used to explore whether statins have an effect on delaying on the onset and progression of age-related macular degeneration (AMD). 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. Overall, there is insufficient evidence to conclude that simvastatin has an effect in delaying the onset and progression of AMD.
ContraindicationsSimvastatin is contraindicated with pregnancy, breastfeeding, and liver disease. 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. High doses of simvastatin are also contraindicated with the widely used antihypertensive amlodipine. A lower dose is also recommended in people taking the calcium channel blockers, verapamil and diltiazem, as well as those taking amiodarone.
Adverse effectsCommon side effects (>1% incidence) may include indigestion and eczema. Rare side effects include joint pain, memory loss, and muscle cramps. Cholestatic hepatitis, hepatic cirrhosis, rhabdomyolysis (destruction of muscles and blockade of renal system), and myositis have been reported in patients receiving the drug chronically.R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1431–3. Serious allergic reactions to simvastatin are rare. If the following signs of a serious allergic reaction occur, seek medical attention immediately: rash, hoarsness itching/swelling, dizziness, or difficulty swallowing/breathing. 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, rs4149056 were at a five-fold or 16-fold increased risk, respectively. In 2012, the Clinical Pharmacogenetics Implementation Consortium has released guidelines regarding the use of rs4149056 genotype in guiding dosing of simvastatin and updated the guideline in 2014. 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. The new guidance indicates:
- FDA has found that liver injury associated with statin use is rare but can occur.
- The reports about memory loss, forgetfulness, and confusion span all statin products and all age groups. The FDA says these experiences are rare but that those affected often report feeling “fuzzy” or unfocused in their thinking.
- A small increased risk of raised blood sugar levels and the development of type 2 diabetes have been reported with the use of statins.
- Some drugs interact with statins in a way that increases the risk of muscle injury called myopathy, characterized by unexplained muscle weakness or pain.