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Rosuvastatin (Crestor®)
| Drug Overview | |
|---|---|
| Drug Class | Statins |
| Mechanism | HMG-CoA Reductase Inhibitor |
| Primary Uses | ASCVD Prevention; Hyperlipidemia |
| Route | Oral |
| Dose Range | 5–40 mg daily |
| Intensity | Moderate–High |
| LDL Reduction | 45–63% |
| Metabolism | Minimal CYP2C9 |
| Half-life | ~19 hours |
| Elimination | Hepatic (minor renal component) |
| Renal Adjustment | Yes (severe CKD) |
| Black Box Warning | No |
| FDA Approval | 2003 |
Overview
Rosuvastatin is a high-potency statin with strong LDL-lowering capability and robust outcome data.
It is one of the most potent statins per milligram and has a lower CYP interaction burden compared to Atorvastatin.
It is frequently selected for high-intensity therapy.
Mechanism of Action
Primary Target:
- HMG-CoA reductase (rate-limiting enzyme in hepatic cholesterol synthesis)
Physiologic Effects:
- ↓ Hepatic cholesterol synthesis
- ↑ LDL receptor expression
- ↑ Circulating LDL clearance
Net Effect:
- Significant LDL reduction
- Plaque stabilization
- Reduced cardiovascular events
LDL lowering is dose-dependent.
Indications
- Secondary prevention after:
Dosing
Moderate-Intensity:
- 5–10 mg daily
High-Intensity:
- 20–40 mg daily
Renal Considerations:
- Start lower doses in severe CKD
- Avoid 40 mg dose in significant renal impairment
Dose selection is based on ASCVD risk category.
Pharmacokinetic Highlights
- Hydrophilic statin
- Minimal CYP metabolism (CYP2C9)
- Lower drug–drug interaction risk compared to Atorvastatin or Simvastatin
- Longer half-life (~19 hours)
Hydrophilicity may reduce muscle penetration relative to lipophilic statins.
Adverse Effects
Muscle:
- Myalgias
- Myositis
- Rare rhabdomyolysis
Hepatic:
- Mild ALT elevation
Metabolic:
- Slight increase in diabetes risk
Risk increases with:
- High doses
- Renal impairment
- Combination with Fibrates (especially Gemfibrozil)
Drug Interactions
Lower CYP interaction burden.
Caution with:
- Severe renal impairment
Less affected by CYP3A4 inhibitors compared to:
Monitoring
- Lipid panel (4–12 weeks after initiation)
- Baseline liver enzymes
- Assess for muscle symptoms
- Renal function in CKD patients
Routine CK monitoring only if symptomatic.
Comparison Within Class
Compared to Atorvastatin:
- More potent per mg
- Fewer CYP interactions
- More hydrophilic
Compared to Pravastatin:
- Much more potent
- Greater LDL reduction
Clinical Role:
- Excellent high-intensity option
- Preferred in patients on multiple interacting medications
High-Yield Pearls
- Most potent statin per mg
- High-intensity therapy at 20–40 mg
- Lower CYP interaction risk
- Requires caution in severe renal impairment
- Strong outcome data in secondary prevention