Introduction
Zocor (simvastatin) is a lipid-lowering medication belonging to the statin class (HMG-CoA reductase inhibitors). It is widely prescribed for the management of dyslipidemia and cardiovascular risk reduction. Originally approved by the FDA in 1991, simvastatin has become one of the most extensively studied and prescribed statins worldwide.
Mechanism of Action
Simvastatin works by competitively inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis in the liver. This inhibition reduces hepatic cholesterol production, leading to upregulation of LDL receptors on hepatocytes. The increased LDL receptor activity enhances clearance of circulating LDL cholesterol and its precursors (VLDL and IDL), resulting in significant reductions in total cholesterol, LDL cholesterol, and triglycerides, with modest increases in HDL cholesterol.
Indications
- Primary hyperlipidemia and mixed dyslipidemia
- Homozygous familial hypercholesterolemia
- Cardiovascular risk reduction in patients with coronary heart disease, diabetes, peripheral artery disease, or history of stroke
- Slowing progression of atherosclerosis
Dosage and Administration
Standard dosing: 5-40 mg once daily in the evening (maximum 40 mg daily; 80 mg restricted to patients previously tolerating this dose)
Administration: Oral, with or without food
Special populations:
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Contraindicated in active liver disease
- Geriatric patients: No dosage adjustment necessary
- Asian patients: Consider lower starting doses due to increased exposure
Pharmacokinetics
Absorption: ~85% oral bioavailability, but extensive first-pass metabolism results in ~5% systemic availability
Distribution: Volume of distribution ~350 L, >95% protein bound
Metabolism: Extensive hepatic metabolism via CYP3A4 isoenzyme
Elimination: Half-life 1.9 hours, primarily excreted in feces (60%) with 13% renal excretion
Contraindications
- Active liver disease or unexplained persistent elevations in serum transaminases
- Pregnancy and breastfeeding
- Concomitant use with strong CYP3A4 inhibitors (itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin, nefazodone)
- Hypersensitivity to simvastatin or any component
Warnings and Precautions
Myopathy/Rhabdomyolysis: Risk increases with higher doses, particularly 80 mg daily
Hepatotoxicity: Monitor liver enzymes before initiation and periodically thereafter
Renal effects: May cause proteinuria and hematuria
Diabetes: May increase HbA1c and fasting glucose
Cognitive effects: Reports of memory loss and confusion
Avoid in patients with unexplained muscle pain, tenderness, or weakness
Drug Interactions
Strong CYP3A4 inhibitors: Contraindicated (increases simvastatin exposure up to 12-fold)
Moderate CYP3A4 inhibitors: Use with caution and dose reduction
Gemfibrozil: Avoid combination (increases risk of myopathy)
Other fibrates: Use with caution
Niacin: Increased risk of myopathy
Warfarin: May enhance anticoagulant effect (monitor INR)
Cyclosporine: Contraindicated with doses >10 mg daily
Amiodarone, verapamil, diltiazem: Limit simvastatin to 10 mg daily
Adverse Effects
Common (>1%): Headache, abdominal pain, constipation, nausea
Less common: Myalgia, elevated transaminases, insomnia
Serious but rare:
- Rhabdomyolysis with renal failure
- Hepatitis/hepatic failure
- Pancreatitis
- Memory loss, confusion
- Peripheral neuropathy
- Immune-mediated necrotizing myopathy
Monitoring Parameters
- Lipid profile: Baseline, 4-12 weeks after initiation/dose change, then every 3-12 months
- Liver enzymes: Baseline, then as clinically indicated
- CK levels: If muscle symptoms occur
- Renal function: Periodically
- HbA1c: In patients with diabetes or risk factors
- Signs/symptoms of myopathy
Patient Education
- Take medication exactly as prescribed, typically in the evening
- Report unexplained muscle pain, tenderness, or weakness immediately
- Avoid grapefruit and grapefruit juice
- Maintain regular follow-up appointments for monitoring
- Continue lifestyle modifications (diet, exercise)
- Inform all healthcare providers about simvastatin use
- Use effective contraception while taking simvastatin
- Be aware of potential interactions with other medications
References
1. FDA Prescribing Information: Zocor (simvastatin) tablets
2. Grundy SM, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. J Am Coll Cardiol. 2019;73(24):e285-e350
3. Thompson PD, et al. Statin-associated side effects. J Am Coll Cardiol. 2016;67(20):2395-2410
4. Cholesterol Treatment Trialists' Collaboration. Efficacy and safety of statin therapy in older people. Lancet. 2019;393(10170):407-415
5. Stroes ES, et al. Statin-associated muscle symptoms: impact on statin therapy. Eur Heart J. 2015;36(17):1012-1022
6. Simvastatin package insert. Merck & Co., Inc. Revised 2021
