What is high dose Crestor (rosuvastatin)?

High-Dose Crestor (Rosuvastatin) Definition

High-dose rosuvastatin (Crestor) is defined as 20-40 mg daily, which achieves ≥50% reduction in LDL cholesterol and is classified as high-intensity statin therapy. 1, 2, 3

Dosing Classification

High-Intensity Rosuvastatin

• Rosuvastatin 20-40 mg daily constitutes high-intensity statin therapy, reducing LDL-C by approximately 50-63% from baseline 1, 3, 4
• The FDA-approved dosage range for rosuvastatin is 5-40 mg orally once daily, with 40 mg being the maximum dose 5
• Rosuvastatin 20 mg is the preferred high-intensity statin option due to superior safety profile compared to simvastatin 80 mg 3

Moderate-Intensity Rosuvastatin (For Context)

• Rosuvastatin 5-10 mg daily is classified as moderate-intensity therapy, achieving 30-49% LDL-C reduction 1, 2

Clinical Indications for High-Dose Rosuvastatin

High-intensity rosuvastatin (20-40 mg) should be initiated in the following patient populations:

Secondary Prevention

• Adults ≤75 years with established ASCVD (acute coronary syndromes, MI, stable/unstable angina, coronary revascularization, stroke, TIA, or peripheral arterial disease) should receive high-intensity statin therapy 1, 2
• High-intensity therapy reduces ASCVD events more than moderate-intensity therapy in patients with clinical ASCVD 1

Primary Prevention

• Patients with LDL-C ≥190 mg/dL should receive high-intensity rosuvastatin regardless of other risk factors 2
• Very high-risk patients with multiple major risk factors, diabetes, severe uncontrolled risk factors, or metabolic syndrome may benefit from intensive LDL lowering to <70 mg/dL 1

Pediatric Populations

• Homozygous familial hypercholesterolemia (HoFH) in patients ≥7 years: 20 mg daily 5
• Heterozygous familial hypercholesterolemia (HeFH) in patients ≥10 years: up to 20 mg daily 5

Important Dosing Modifications

Population-Specific Adjustments

• Asian patients: Initiate at 5 mg daily due to increased plasma concentrations; carefully consider risks/benefits when exceeding 20 mg daily 5
• Severe renal impairment (CrCl <30 mL/min/1.73 m² not on hemodialysis): Start at 5 mg daily, do not exceed 10 mg daily 5

Drug Interaction Limitations

The following concomitant medications restrict maximum rosuvastatin dosing: 5

• Cyclosporine: Do not exceed 5 mg daily
• Gemfibrozil: Avoid concomitant use; if necessary, do not exceed 10 mg daily
• Teriflunomide, enasidenib, capmatinib: Do not exceed 10 mg daily
• Fostamatinib, febuxostat: Do not exceed 20 mg daily
• Multiple antivirals (atazanavir/ritonavir, lopinavir/ritonavir, glecaprevir/pibrentasvir): Do not exceed 10 mg daily

Comparative Efficacy

Rosuvastatin demonstrates superior LDL-C lowering compared to other statins at equivalent doses:

• Rosuvastatin 10 mg produces significantly greater LDL-C reduction than atorvastatin 10 mg, simvastatin 20 mg, or pravastatin 40 mg 2, 4, 6
• At 10-40 mg doses, rosuvastatin reduces LDL-C by 52-63%, increases HDL-C by up to 14%, and reduces triglycerides by up to 28% 4, 6

Safety Profile

High-dose rosuvastatin has an acceptable safety profile comparable to other statins:

• Myopathy incidence is <0.1% at recommended doses of 5-40 mg daily 2
• Slight increased risk of new-onset diabetes, particularly in patients with metabolic syndrome features 2
• No consistent pattern of renal failure or injury, despite mild transient tubular proteinuria 7
• Safety profile similar to other marketed statins based on evaluation in >10,000 patients 8

Common Pitfalls to Avoid

• Never initiate simvastatin 80 mg as an alternative to high-intensity therapy due to FDA warnings about myopathy risk; use rosuvastatin 20 mg instead 3
• Do not overlook drug interactions that may necessitate dose limitations, particularly with cyclosporine, gemfibrozil, and multiple antivirals 5
• Assess LDL-C as early as 4 weeks after initiating therapy and adjust dosage accordingly 5
• For patients >75 years with ASCVD, moderate-intensity therapy may be more appropriate as there was no clear evidence of additional ASCVD event reduction from high-intensity therapy in this age group 1