pharmacopeia
GET
/api/v1/drug/simvastatin
2D structure
[(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] 2,2-dimethylbutanoate
SMILES CCC(C)(C)C(=O)O[C@H]1C[C@H](C=C2[C@H]1[C@H]([C@H](C=C2)C)CC[C@@H]3C[C@H](CC(=O)O3)O)C
InChIKey RYMZZMVNJRMUDD-HGQWONQESA-N

Mechanism of action

Sourced from openFDA

Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin acid and its metabolites are inhibitors of HMG-CoA reductase, the rate-limiting enzyme that converts HMG-CoA to mevalonate, a precursor of cholesterol.

Cytochrome P450 3A4HIV ProteaseHydroxymethylglutaryl-CoA Reductase

Indications

Sourced from openFDA
  • Simvastatin tablets USP are indicated: To reduce the risk of total mortality by reducing risk of coronary heart disease death, non-fatal myocardial infarction and stroke, and the need for coronary and non-coronary revascularization procedures in adults with established coronary heart disease, cerebrovascular disease, peripheral vascular disease, and/or diabetes, who are at high risk of coronary heart disease events. As an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C): In adults with primary hyperlipidemia.ICD-10: E78.5, I21.9, I63.9

Contraindications

Sourced from openFDA
  • Simvastatin is contraindicated in the following conditions: Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see DRUG INTERACTIONS ( 7.1 )]. Concomitant use of cyclosporine, danazol or gemfibrozil [see DRUG INTERACTIONS ( 7.1 )].contraindicated

Dosage & administration

Sourced from openFDA

Important Dosage and Administration Information : ( 1 ) Take simvastatin tablets USP orally once daily in the evening. Maximum recommended dosage is simvastatin tablets USP 40 mg once daily. An 80 mg daily dosage of simvastatin tablets USP is restricted to patients who have been taking simvastatin tablets USP 80 mg daily chronically (e.g., for 12 months or more) without evidence of muscle toxicity. For patients that require a high-intensity statin or are unable to achieve their LDL-C goal receiving simvastatin tablets USP 40 mg daily, prescribe alternative LDL-C lowering treatment. Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating, and adjust the dosage if necessary. Adults : Recommended dosage is 20 mg to 40 mg once daily. ( 2.2 ) Pediatric Patients Aged 10 Years and Older with HeFH : Recommended dosage is 10 mg to 40 mg once daily. ( 2.3 ) Patients with Severe Renal Impairment : Recommended starting dosage is simvastatin 5 mg once daily. ( 2.4 , 8.6 ) See full prescribing information for simvastatin tablets USP dosage modifications due to drug interactions. ( 2.5 ) 2.1 Important Dosage and Administration Information Take simvastatin tablets USP orally once daily in the evening. The maximum recommended dosage is simvastatin tablets USP 40 mg once daily [see DOSAGE AND ADMINISTRATION ( 2.2 , 2.3 )]. An 80 mg daily dosage of simvastatin tablets USP is restricted to patients who have been taking simvastatin tablets USP 80 mg daily chronically (e.g., for 12 months or more) without evidence of muscle toxicity [see WARNINGS AND PRECAUTIONS ( 5.1 )].

Warnings & precautions

Sourced from openFDA

Myopathy and Rhabdomyolysis: Risk factors include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher simvastatin dosage. Chinese patients may be at higher risk for myopathy. Discontinue simvastatin if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Temporarily discontinue simvastatin in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis. Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing simvastatin dosage. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. ( 5.1 , 7.1 , 8.5 , 8.6 , 8.8 ) Immune-Mediated Necrotizing Myopathy (IMNM): Rare reports of IMNM, an autoimmune myopathy, have been reported. Discontinue simvastatin if IMNM is suspected. ( 5.2 ) Hepatic Dysfunction: Increases in serum transaminases have occurred, some persistent. Rare reports of fatal and non-fatal hepatic failure have occurred. Consider testing liver enzyme before initiating therapy and as clinically indicated thereafter. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue simvastatin. ( 4 , 5.3 , 8.7 ) 5.1 Myopathy and Rhabdomyolysis Simvastatin may cause myopathy and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including simvastatin.

Adverse reactions

Sourced from openFDA

The following important adverse reactions are described below and elsewhere in the labeling: Myopathy and Rhabdomyolysis [see WARNINGS AND PRECAUTIONS ( 5.1 )] Immune-Mediated Necrotizing Myopathy [see WARNINGS AND PRECAUTIONS ( 5.2 )] Hepatic Dysfunction [see WARNINGS AND PRECAUTIONS ( 5.3 )] Increases in HbA1c and Fasting Serum Glucose Levels [see WARNINGS AND PRECAUTIONS ( 5.4 )] Most common adverse reactions (incidence ≥5%) are: upper respiratory infection, headache, abdominal pain, constipation, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. In clinical studies, 2,423 adult patients were exposed to simvastatin with a median duration of follow-up of approximately 18 months. The most commonly reported adverse reactions (incidence ≥5%) in these simvastatin clinical studies were: upper respiratory infections (9%), headache (7%), abdominal pain (7%), constipation (7%), and nausea (5%). Overall, 1.4% of patients discontinued simvastatin due to adverse reactions. The most common adverse reactions that led to discontinuation were: gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia (0.1%).

Use in specific populations

Sourced from openFDA

Pregnancy: May cause fetal harm. ( 8.1 ) Lactation: Breastfeeding not recommended during treatment with simvastatin. ( 8.2 ) 8.1 Pregnancy Risk Summary Discontinue simvastatin when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Simvastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, simvastatin may cause fetal harm when administered to pregnant patients based on the mechanism of action [see CLINICAL PHARMACOLOGY ( 12.1 )] . In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. Published data from prospective and retrospective observational cohort studies with simvastatin use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see Data).

Pharmacokinetics

Sourced from openFDA
Metabolism
Simvastatin is a lactone that is readily hydrolyzed in vivo to the corresponding β-hydroxyacid. Pharmacokinetics (PK) of simvastatin and its metabolites was originally characterized using inhibition of HMG-CoA reductase activity following base hydrolysis of plasma samples, as specific bioanalytical methods were not available.

Overdosage

Sourced from openFDA

No specific antidotes for simvastatin are known. Contact Poison Control (1-800-222-1222) for latest recommendations.

Approval history

Sourced from openFDA
  • Dec 23, 1991NDANDA019766Organon
  • Jul 23, 2004NDANDA021687Organon
  • Dec 20, 2006ANDAANDA077691Aurobindo Pharma
  • Dec 20, 2006ANDAANDA078034Biocon Pharma
  • May 11, 2007ANDAANDA078103Lupin
  • Feb 26, 2008ANDAANDA078155Accord Hlthcare
  • Sep 16, 2011ANDAANDA090383Micro Labs
  • Nov 25, 2014ANDAANDA200895Hetero Labs Ltd Iii

FAERS reports

View JSON
Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
261,343 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Fatigue14,3795.5%
  2. 2Nausea13,9685.3%
  3. 3Dyspnoea13,0965.0%
  4. 4Diarrhoea12,4414.8%
  5. 5Drug Ineffective12,1994.7%
  6. 6Dizziness11,7254.5%
  7. 7Pain9,7553.7%
  8. 8Asthenia9,7383.7%
  9. 9Fall9,6573.7%
  10. 10Headache9,4083.6%
  11. 11Myalgia9,0023.4%
  12. 12Vomiting8,5863.3%
  13. 13Arthralgia8,0993.1%
  14. 14Malaise7,9873.1%
  15. 15Pain In Extremity7,4742.9%

Literature

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Recent PubMed references pinned to Simvastatin as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 672 ClinicalTrials.gov registrations naming Simvastatin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Pharmacogenomics

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CPIC-curated drug–gene pairs for Simvastatin. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

Structural analogs

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Ranked by 2D fingerprint (Tanimoto) similarity over PubChem structures. Structural proximity only — not a claim of therapeutic equivalence.

Frequently asked questions

How does Simvastatin work?
Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin acid and its metabolites are inhibitors of HMG-CoA reductase, the rate-limiting enzyme that converts HMG-CoA to mevalonate, a precursor of cholesterol.
What is Simvastatin used for?
According to FDA labeling, Simvastatin carries indications including: Simvastatin tablets USP are indicated: To reduce the risk of total mortality by reducing risk of coronary heart disease death, non-fatal myocardial infarction and stroke, and the need for coronary and non-coronary revascularization procedures in adults with established coronary heart disease, cerebrovascular disease, peripheral vascular disease, and/or diabetes, who are at high risk of coronary heart disease events. As an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C): In adults with primary hyperlipidemia.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Simvastatin?
Simvastatin is classified as HMG CoA reductase inhibitors, HMG-CoA Reductase Inhibitor, Cytochrome P450 3A4 Inhibitors, HIV Protease Inhibitors, Hydroxymethylglutaryl-CoA Reductase Inhibitors.
What are the brand names for Simvastatin?
Simvastatin is marketed under brand names including Flolipid, Vytorin, Zocor.
What are the contraindications for Simvastatin?
Simvastatin labeling lists contraindications including: Simvastatin is contraindicated in the following conditions: Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see DRUG INTERACTIONS ( 7.1 )]. Concomitant use of cyclosporine, danazol or gemfibrozil [see DRUG INTERACTIONS ( 7.1 )].. Always consult the full prescribing information and a clinician.
Note. Data for simvastatin is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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