simvastatin (Rx)

Brand and Other Names:Zocor
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 5mg
  • 10mg
  • 20mg
  • 40mg
  • 80mg
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Hypercholesterolemia

Usual dosage range: 5-40 mg PO qDay

Initial: 10-20 mg PO qDay in the evening

Patients at high CHD risk: Start 40 mg/day

Homozygous Familial Hypercholesterolemia

Recommended dose: 40 mg PO qDay in the evening

See limitations for 80 mg/day, listed below

Prevention of Coronary Events

5-40 mg PO qDay in the evening

Moderate reduction of LDL-C desired: 5-10 mg PO qDay in the evening; adjust dose to achieve goal

Reduction of >40% of LDL-C desired: 40 mg PO qDay in the evening; adjust dose to achieve goal

Presence of CHD or at high risk for cardiovascular events, including patients with diabetes, PVD, history of stroke or other cerebrovascular disease: 40 mg PO qDay in the evening adjunct to diet therapy (initiate simultaneously); adjust dose to achieve goal

Primary and secondary prevention of atheroschlerotic cardiovascular disease (ASCVD)

ACC/AHA Cholesterol Guideline Recommendations (2013) for adults ≥21 years

Primary prevention

  • LDL-C ≥190 mg/dL: High-intensity therapy agent atorvastatin or rosuvastatin recommended
  • Type 1 or 2 diabetes (40-75 years of age): Moderate-intensity therapy: 20-40 mg simvastatin PO qDay
  • Type 1 or 2 diabetes (40-75 years of age and 10 year estimated risk of ASCVD ≥7.5%): High-intensity therapy agent atorvastatin or rosuvastatin recommended
  • 40-75 years of age and 10 year estimated risk of ASCVD ≥7.5% : Moderate-intensity therapy: 20-40 mg simvastatin PO qDay; may consider high-intensity therapy agent atorvastatin or rosuvastatin

Secondary prevention

  • Presence of ASCVD, including stroke/TIA or peripheral arterial disease believed to be of atherosclerotic origin or post-CABG
  • ≤75 years: Treat with high-intensity therapy agent atorvastatin or rosuvastatin
  • >75 years: Administer 20-40 mg simvastatin PO qDay (moderate-intensity therapy); not candidate for high-intensity therapy

Dosage Modifications

Severe renal impairment (CrCl <30 mL/min): 5 mg qDay initially

Coadministration with dronedarone, verapamil, or diltiazem: Do not exceed 10 mg/day

Coadministration with amiodarone, amlodipine, or ranolazine: Do not exceed 20 mg/day

Coadministration with lomitapide: Reduce simvastatin dose by 50%, and do not exceed 20 mg/day (or 40 mg/day in those previously tolerating 80 mg/day) when initiating lomitapide

Patients of Chinese descent taking lipid-modifying doses of niacin (ie, ≥1 g/day): Increased risk of myopathy with simvastatin 40 mg/day; consider lower dose

Patients of Asian descent should not receive simvastatin 80 mg coadministered with lipid-modifying doses of niacin-containing products

Dosing Considerations

Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter

Restricted dosing

  • 80 mg/day should be used only for individuals who have been taking simvastatin 80 mg chronically (eg, ≥12 months) without evidence of myopathy or rhabdomyolysis
  • Patients tolerating 80 mg who need to be initiated on an interacting drug that is contraindicated or associated with a maximum dose for simvastatin should be switched to an alternative statin with less potential for drug-drug interactions
  • Patients unable to achieve their LDL-C goal utilizing 40 mg/day should not be titrated to 80 mg (increased risk for myopathy) but should instead be placed on alternative LDL-C-lowering treatment that provides greater LDL-C lowering

Overdose management

  • Adverse drug reactions from overdose may include peripheral neuropathy, diarrhea, increased K+, myopathy, rhabdomyolysis, acute renal failure, elevated LFTs, and eye lens opacities
  • Treatment is supportive

Dosage Forms & Strengths

tablet

  • 5mg
  • 10mg
  • 20mg
  • 40mg
  • 80mg
more...

Hypercholesterolemia

<10 years: Safety and efficacy not established

Heterozygous Familial Hypercholesterolemia

Adolescents aged 10-17 years

  • Initial: 10 mg PO qDay in the evening; not to exceed 40 mg/day
  • Recommended dosing range: 10-40 mg/day; adjustments should be made at intervals of 4 weeks or more
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Interactions

Interaction Checker

and simvastatin

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            1-10%

            CPK elevation (>3x ULN) (5%)

            Constipation (2%)

            Upper respiratory infection (9%)

            Flatulence (1-2%)

            Transaminases increased (>3x ULN) (1%)

            Headache (3-7%)

            Myalgia (5%)

            Eczema (5%)

            Vertigo (5%)

            Abdominal pain (7%)

            <1%

            Myalgia

            Myopathy

            Arthralgia

            Arthritis

            Eosinophilia

            Chills

            Angioedema

            Rhabdomyolysis

            Abdominal pain

            Postmarketing Reports

            Erectile dysfunction

            Interstitial lung disease

            Rare reports of cognitive impairment (eg, memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use

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            Warnings

            Contraindications

            Hypersensitivity to simvastatin

            Active liver disease or unexplained transaminase elevation

            Pregnancy

            Nursing mothers

            Strong CYP3A4 inhibitors (eg, itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, posaconazole, voriconazole, HIV protease inhibitors, cobicistat, nefazodone, boceprevir, telaprevir), gemfibrozil, cyclosporine, and danazol

            Cautions

            Rule out secondary causes of hyperlipidemia prior to initiating therapy

            Nonserious and reversible cognitive side effects may occur

            Increased blood sugar and glycosylated hemoglobin (HbA1c) levels reported with statin intake

            Heavy alcohol use, history of liver disease, renal failure

            Monitor LFTs before initiating treatment and thereafter when clinically indicated; reports of fatal and nonfatal hepatic failure in patients taking statins

            Discontinue if markedly elevated CPK levels occur or myopathy is diagnosed or suspected

            Increases in HbA1c and fasting serum glucose levels reported with simvastatin

            Severe electrolyte, endocrine, or metabolic disorders

            Grapefruit juice increases simvastatin systemic exposure; avoid large quantities of grapefruit juice (ie, ≥1 quart/day)

            Simvastatin and myopathy risk

            • Myopathy/rhabodomyolysis with acute renal failure and/or myopathy reported; monitor patient closely Dose adjustment required when coadministered with niacin, amiodarone, verapamil, diltiazem, amlodipine, and ranolazine
            • Predisposing factors for myopathy include advanced age (>65 years), uncontrolled hypothyroidism, and renal impairment
            • Increased risk for myopathy in Chinese patients coadministered niacin >1 g/day; they should not receive simvastatin 80 mg coadministered with lipid-modifying doses of niacin-containing products
            • Withhold or discontinue if myopathy, renal failure, or transaminase levels >3x ULN develop
            • Risk of myopathy is greater in patients taking simvastatin 80 mg/day, especially in the 1st year of treatment
            • Rare reports of immune-mediated necrotizing myopathy (IMNM), characterized by increased serum creatine kinase that persists despite discontinuing statin
            • Risk for myopathy increased when coadministered with other lipid-lowering drugs (other fibrates, ≥1 g/day of niacin, or, for patients with HoFH, lomitapide), colchicine, amiodarone, dronedarone, verapamil, diltiazem, amlodipine, or ranolazine
            • See Contraindications for list of drugs contraindicated because of increased risk for myopathy when coadministered with simvastatin
            • See Adult Dosing for dose limitations and modifications
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            Pregnancy & Lactation

            Pregnancy category: X

            Lactation: Contraindicated; potentially unsafe

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            HMG-CoA reductase inhibitor; inhibits the rate-limiting step in cholesterol biosynthesis by competitively inhibiting HMG-CoA reductase

            Absorption

            Bioavailability: <5%

            Onset of action: >3 days

            Peak plasma time: 1.3-2.4 hr

            Maximum effect: 4-6 weeks

            Distribution

            Protein bound: 95%

            Metabolism

            First pass in liver

            Converted to maximally active simvastatin acid by nonenzymatic pathways and nonspecific enzymes

            Metabolites: Beta-hydroxyacid and 6'-hydroxy, 6'-hydroxymethyl, and 6'-exomethylene derivatives (all active)

            Simvastatin acid also converted to other active metabolites by CYP3A4

            Elimination

            Excretion: Feces (60%); urine (13%)

            Pharmacogenomics

            SLCO1B1 (OATP1B1) CC genotype significantly increases AUCs of parent drug and metabolites compared with the CT or TT genotypes

            This polymorphism is proposed to reduce transport into the liver, the main site of statin metabolism and elimination, resulting in elevated plasma concentrations

            SLCO1B1 polymorphism is thought to have a lesser effect on the more hydrophilic statins (eg, rosuvastatin, fluvastatin) compared with those that are more lipophilic (eg, atorvastatin, simvastatin)

            Other genetic polymorphisms of elimination (eg, CYP450, P-glycoprotein) for each individual drug must also be considered, to explain variability for statin clearance among patients that exhibit SCLO1B1 polymorphism

            SLCO1B1 CC genotype is most common in Caucasians and Asians (15%)

            Risk of myopathy is 2.6- to 4.3-fold higher if the C allele is present and 16.9-fold higher in CC homozygotes than in TT homozygotes

            Genetic testing laboratories

            • Optivia Biotechnology, Inc (http://optiviabio.com)
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            Formulary

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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