II. Indications

  1. See Hyperlipidemia Management for formal criteria
  2. See Statin
  3. Hyperlipidemia
  4. Primary of vascular disease progression (e.g. CAD, CVA, DM, CKD, PAD)

III. Contraindications

  1. See Statin
  2. Drug Interactions
    1. See Statin regarding Myopathy and hepatitis risk
  3. Pregnancy (Teratogen)
  4. Acute Liver Failure or decompensated Cirrhosis

IV. Mechanism

  1. See Statin

V. Efficacy

  1. See Statin
  2. Simvastatin 5 mg lowers LDL 26%
  3. Simvastatin 10 mg lowers LDL 28 to 29%
  4. Simvastatin 20 mg lowers LDL 35 to 38% (recommended starting dose)
  5. Simvastatin 40 mg lowers LDL 30 to 41% (maximum dose recommended in U.S. as of 2011)
  6. Simvastatin 80 mg lowers LDL 36 to 48% (dose no longer recommended due to complications)

VI. Adverse Effects

VII. Safety

  1. Pregnancy Category X
  2. Contraindicated in Lactation

VIII. Pharmacokinetics

  1. See Statin
  2. Undergoes first pass metabolism as with most Statins (except Pravastatin)
  3. Protein binding
    1. As with most Statins (except Pravastatin), Simvastatin is 90% Protein bound
  4. Cytochrome P450 Metabolism
    1. CYP3A4 isoenzyme metabolizes most Statins, including Simvastatin

IX. Dosing: Adult

  1. Specific LDL and HDL targets have been replaced with high-intensity Statin if 10 year Cardiovascular Risk >20%
  2. Low intensity Statin (age >75 years, or Statin intolerant)
    1. Simvastatin 20 to 40 mg orally daily

X. Dosing: Child

  1. Approved for children age 10 years and older
  2. Start 10 mg orally daily
  3. Maximum 40 mg/day

XI. Monitoring

  1. See Statin
  2. Liver transaminase testing (AST,ALT) is no longer routinely indicated as of March 2012

XII. Drug Interactions (See Contraindications above)

  1. See Statin
  2. CYP3A4 Inhibitors
    1. Azole Antifungals (Intraconazole, Ketoconazole - 10-20 fold increase in Statin serum levels)
      1. Increased risk of Statin Myopathy (esp. with age >65, Obesity, renal or liver Impairment)
      2. Avoid with Simvastatin
    2. Calcium Channel Blocker
      1. Diltiazem (limit to 240 mg daily)
        1. Avoid with Simvastatin over 10 mg daily
      2. Verapamil (6-10 fold increase in Statin serum levels)
        1. Avoid with Simvastatin over 10 mg daily
      3. Amlodipine (Norvasc)
        1. Avoid with Simvastatin over 20 mg daily
    3. Grapefruit juice increases some Statin levels
      1. Simvastatin is among the drugs most affected
        1. Avoid with any Grapefruit juice (or minimal use)
      2. References
        1. (2016) Presc Lett 23(3):18
        2. Reamy (2007) Am Fam Physician 76:190-1 [PubMed]
  3. CYP3A4/organic anion transporting polypeptide inhibitors
    1. Protease inibitors (Atazanavir, Ritonavir, Lopinavir/Ritonavir)
      1. Avoid with Simvastatin
  4. CYP3A4/CYP2C9 Inhibitor
    1. Amiodarone
      1. Increased risk of Statin Myopathy (esp. with age >65, Obesity, renal or liver Impairment)
      2. Avoid with Simvastatin over 20 mg daily
    2. Warfarin (Increased INR and bleeding risk)
      1. Among the highest risk with Simvastatin
  5. CYP2C9, CYP2C19/oragnic anion transporting polypeptide inhibitors
    1. Gemfibrozil (2-3 fold increase in Statin serum levels, >13 fold increase in Rhabdomyolysis risk)
      1. Avoid with Simvastatin over 10 mg daily
  6. Other interactions
    1. Mibefradil (Posicor)
    2. Niacin
    3. Alcohol
      1. Increases risk of liver enzyme elevations

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Related Studies

Cost: Medications

simvastatin (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
SIMVASTATIN 10 MG TABLET Generic $0.03 each
SIMVASTATIN 20 MG TABLET Generic $0.02 each
SIMVASTATIN 40 MG TABLET Generic $0.04 each
SIMVASTATIN 5 MG TABLET Generic $0.02 each
SIMVASTATIN 80 MG TABLET Generic $0.09 each