Simvastatin (Zocor®)
| Drug Overview |  |
|---|---|
| Drug Class | Statins |
| Mechanism | HMG-CoA Reductase Inhibitor |
| Primary Uses | Hyperlipidemia; ASCVD Prevention |
| Route | Oral |
| Dose Range | 10–40 mg daily |
| Intensity | Low–Moderate |
| LDL Reduction | 25–45% |
| Metabolism | CYP3A4 |
| Half-life | ~2–3 hours (active metabolites longer) |
| Elimination | Hepatic |
| Renal Adjustment | No (caution in severe CKD) |
| Black Box Warning | No |
| FDA Approval | 1991 |
Overview
Simvastatin is a first-generation statin used for LDL reduction and ASCVD prevention.
It is less potent than Atorvastatin and Rosuvastatin, and carries a higher drug–drug interaction risk due to CYP3A4 metabolism.
The 80 mg dose is no longer recommended due to increased myopathy risk.
Mechanism of Action
Primary Target:
- HMG-CoA reductase (rate-limiting step in hepatic cholesterol synthesis)
Physiologic Effects:
- ↓ Hepatic cholesterol production
- ↑ LDL receptor expression
- ↑ Circulating LDL clearance
Net Effect:
- Moderate LDL reduction
- Reduced cardiovascular events
LDL lowering is dose-dependent.
Indications
- Secondary prevention after:
Dosing
Low-Intensity:
- 10 mg daily
Moderate-Intensity:
- 20–40 mg daily
Important:
- 80 mg dose should NOT be initiated
- Use 80 mg only if patient has tolerated long-term without adverse effects
Dose selection is based on ASCVD risk category.
Pharmacokinetic Highlights
- Lipophilic statin
- Extensively metabolized by CYP3A4
- Higher drug–drug interaction burden
- Shorter half-life compared to Atorvastatin and Rosuvastatin
Due to lipophilicity, may have greater muscle penetration.
Adverse Effects
Muscle:
- Myalgias
- Myositis
- Increased risk of rhabdomyolysis (dose-dependent)
Hepatic:
- Mild ALT elevation
Metabolic:
- Slight increase in diabetes risk
Myopathy risk increases with:
- High dose (especially 80 mg)
- CYP3A4 inhibitors
- Combination with Fibrates (especially Gemfibrozil)
Drug Interactions
High interaction risk due to CYP3A4 metabolism.
Avoid or use caution with:
- Macrolide antibiotics
- Azole antifungals
- Protease inhibitors
- Grapefruit juice
Higher myopathy risk when combined with:
Compared to:
- Rosuvastatin — higher interaction burden
- Pravastatin — significantly higher interaction burden
Monitoring
- Lipid panel (4–12 weeks after initiation)
- Baseline liver enzymes
- Monitor for muscle symptoms
CK only if symptomatic.
Comparison Within Class
Compared to Atorvastatin:
- Less potent
- Higher CYP interaction risk
- Lower LDL reduction at maximal dose
Compared to Rosuvastatin:
- Significantly less potent
- More drug interactions
- Shorter half-life
Clinical Role:
- Appropriate moderate-intensity option
- Less favored when high-intensity therapy is indicated
High-Yield Pearls
- Avoid initiating 80 mg dose
- CYP3A4 interactions are clinically significant
- Lipophilic statin with moderate potency
- Consider alternative statins in polypharmacy patients
- Still effective for moderate-risk ASCVD prevention