Simvastatin

ATC code

C10AA01

Therapeutic class

Statin (HMG-CoA reductase inhibitor) · HMG-CoA reductase inhibitor

Forms

oral tablet

Brand names

Zocor (US) · Simvastatina Cinfamed (ES)

Overall confidence

high

Regulatory sources consulted

Approved indications

Adjunctive therapy to diet to reduce elevated cholesterol in individuals at significantly increased risk for atherosclerotic vascular disease. In patients with coronary heart disease (CHD) or at high risk of CHD, simvastatin can be started simultaneously with diet.

Contraindications

Absolute

Concomitant use of strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, nefazodone).
Concomitant use of gemfibrozil, cyclosporine, or danazol.
Active liver disease or unexplained persistent elevations of serum transaminases.
Pregnancy and lactation.
Hypersensitivity to any component of the medication.

Clinical warnings

Major warning · Myopathy/Rhabdomyolysis: Increased risk of myopathy and rhabdomyolysis with high doses (80-mg dose is restricted), advanced age, renal impairment, and certain drug interactions. Discontinue if myopathy is suspected or diagnosed. — FDA

Drug interactions

HighStrong CYP3A4 inhibitorsJ02AC02
Mechanism: Inhibition of simvastatin metabolism via CYP3A4, drastically increasing its exposure and the risk of myopathy/rhabdomyolysis.
Recommendation: Concomitant use is contraindicated.
DailyMed SPL 593f0007-9690-4de5-b1e9-59299e587643
HighCyclosporineL04AD01
Mechanism: Multifactorial mechanism, including inhibition of OATP1B1 and CYP3A4, which significantly increases simvastatin exposure.
Recommendation: Concomitant use is contraindicated.
DailyMed SPL 593f0007-9690-4de5-b1e9-59299e587643
HighAmiodaroneC01BD01
Mechanism: Inhibition of simvastatin metabolism (possibly via CYP3A4), increasing the risk of myopathy.
Recommendation: Do not exceed 20 mg of simvastatin daily.
DailyMed SPL 593f0007-9690-4de5-b1e9-59299e587643

Adverse events

Common (≥1%)

upper respiratory infection · headache · abdominal pain · constipation · nausea

Rare but serious

rhabdomyolysis · hepatotoxicity · myopathy

Pregnancy and lactation

FDA category: X

Contraindicated in pregnancy. Statins decrease cholesterol synthesis, which is essential for fetal development. If a patient becomes pregnant, simvastatin should be discontinued immediately. Contraindicated in nursing mothers due to the potential for serious adverse reactions in the nursing infant.