II. Indications
- See Hyperlipidemia Management for formal criteria
- See Statin
- Hyperlipidemia
- Primary of vascular disease progression (e.g. CAD, CVA, DM, CKD, PAD)
III. Contraindications
- See Statin
- Drug Interactions
- Pregnancy (Teratogen)
- Acute Liver Failure or decompensated Cirrhosis
IV. Mechanism
- See Statin
V. Efficacy
- See Statin
- Simvastatin 5 mg lowers LDL 26%
- Simvastatin 10 mg lowers LDL 28 to 29%
- Simvastatin 20 mg lowers LDL 35 to 38% (recommended starting dose)
- Simvastatin 40 mg lowers LDL 30 to 41% (maximum dose recommended in U.S. as of 2011)
- Simvastatin 80 mg lowers LDL 36 to 48% (dose no longer recommended due to complications)
VI. Adverse Effects
- See Statin
- See Statin-Induced Myopathy
VII. Safety
- Pregnancy Category X
- Contraindicated in Lactation
VIII. Pharmacokinetics
- See Statin
- Undergoes first pass metabolism as with most Statins (except Pravastatin)
-
Protein binding
- As with most Statins (except Pravastatin), Simvastatin is 90% Protein bound
- Cytochrome P450 Metabolism
IX. Dosing: Adult
- Specific LDL and HDL targets have been replaced with high-intensity Statin if 10 year Cardiovascular Risk >20%
- Low intensity Statin (age >75 years, or Statin intolerant)
- Simvastatin 20 to 40 mg orally daily
X. Dosing: Child
- Approved for children age 10 years and older
- Start 10 mg orally daily
- Maximum 40 mg/day
XI. Monitoring
XII. Drug Interactions (See Contraindications above)
- See Statin
-
CYP3A4 Inhibitors
- Azole Antifungals (Intraconazole, Ketoconazole - 10-20 fold increase in Statin serum levels)
- Increased risk of Statin Myopathy (esp. with age >65, Obesity, renal or liver Impairment)
- Avoid with Simvastatin
- Calcium Channel Blocker
- Diltiazem (limit to 240 mg daily)
- Avoid with Simvastatin over 10 mg daily
- Verapamil (6-10 fold increase in Statin serum levels)
- Avoid with Simvastatin over 10 mg daily
- Amlodipine (Norvasc)
- Avoid with Simvastatin over 20 mg daily
- Diltiazem (limit to 240 mg daily)
- Grapefruit juice increases some Statin levels
- Simvastatin is among the drugs most affected
- Avoid with any Grapefruit juice (or minimal use)
- References
- (2016) Presc Lett 23(3):18
- Reamy (2007) Am Fam Physician 76:190-1 [PubMed]
- Simvastatin is among the drugs most affected
- Azole Antifungals (Intraconazole, Ketoconazole - 10-20 fold increase in Statin serum levels)
-
CYP3A4/organic anion transporting polypeptide inhibitors
- Protease inibitors (Atazanavir, Ritonavir, Lopinavir/Ritonavir)
- Avoid with Simvastatin
- Protease inibitors (Atazanavir, Ritonavir, Lopinavir/Ritonavir)
-
CYP3A4/CYP2C9 Inhibitor
- Amiodarone
- Increased risk of Statin Myopathy (esp. with age >65, Obesity, renal or liver Impairment)
- Avoid with Simvastatin over 20 mg daily
- Warfarin (Increased INR and bleeding risk)
- Among the highest risk with Simvastatin
- Amiodarone
-
CYP2C9, CYP2C19/oragnic anion transporting polypeptide inhibitors
- Gemfibrozil (2-3 fold increase in Statin serum levels, >13 fold increase in Rhabdomyolysis risk)
- Avoid with Simvastatin over 10 mg daily
- Gemfibrozil (2-3 fold increase in Statin serum levels, >13 fold increase in Rhabdomyolysis risk)
- Other interactions
- Mibefradil (Posicor)
- Niacin
- Alcohol
- Increases risk of liver enzyme elevations
XIII. Resources
- See Statin
- Simvastatin (DailyMed)
XIV. References
- (2017) Presc Lett 24(11): 62
- (2012) Presc Lett 19(5): 25
- (2012) Presc Lett, Characteristics of Various Statins, #280502
- Carpenter (2019) Am Fam Physician 99(9):558-64 [PubMed]
- Chong (2001) Am J Med 111:390-400 [PubMed]
- Crouch (2001) Am Fam Physician 63(2):309-20 [PubMed]
- Gillett (2011) Am Fam Physician 83(6): 711-6 [PubMed]
- Jones (1998) Am J Cardiol 81:582-7 [PubMed]
- Sasaki (1998) Clin Ther 20:539-48 [PubMed]
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Related Studies
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 |