What is the maximum recommended dose of Crestor (rosuvastatin)?

Maximum Recommended Dose of Crestor (Rosuvastatin)

The maximum recommended dose of Crestor (rosuvastatin) is 40 mg once daily for most patients, though this dose should be reserved for patients with severe hypercholesterolemia who have not achieved their LDL-C goals on lower doses. 1

Standard Dosing Range

• The FDA-approved dosage range for rosuvastatin is 5 mg to 40 mg orally once daily 1
• Rosuvastatin can be taken at any time of day, with or without food 1
• The 40 mg dose is primarily indicated for patients with severe familial hypercholesterolemia or those requiring maximal LDL-C reduction 1, 2

Important Dose Restrictions Based on Drug Interactions

Several commonly used cardiovascular and other medications require mandatory dose limitations of rosuvastatin to prevent severe muscle toxicity:

Severe Restrictions (Maximum 5 mg daily):

• Cyclosporine: Do not exceed 5 mg once daily due to 7-fold increase in rosuvastatin exposure 1, 3, 4
• Darolutamide: Maximum 5 mg once daily 1

Moderate Restrictions (Maximum 10 mg daily):

• Teriflunomide, enasidenib, capmatinib: Do not exceed 10 mg once daily 1
• Gemfibrozil: Avoid concomitant use if possible; if used together, initiate at 5 mg and do not exceed 10 mg once daily 1
• Regorafenib: Maximum 10 mg once daily 1
• Multiple antiretroviral agents (atazanavir/ritonavir, lopinavir/ritonavir): Initiate at 5 mg and do not exceed 10 mg once daily 1

Less Severe Restrictions (Maximum 20 mg daily):

• Fostamatinib, febuxostat: Do not exceed 20 mg once daily 1
• Tafamidis: Avoid concomitant use if possible; if used together, initiate at 5 mg and do not exceed 20 mg once daily 1
• When used with resmetirom (for MASH/NASH): Rosuvastatin should be limited to 20 mg daily 5

Special Population Considerations

Asian Patients:

• Initiate at 5 mg once daily due to increased rosuvastatin plasma concentrations in Asian populations 1
• Consider risks and benefits carefully when treating Asian patients not adequately controlled at doses up to 20 mg once daily 1

Severe Renal Impairment:

• In patients with severe renal impairment (CrCl <30 mL/min/1.73 m²) not on hemodialysis, start at 5 mg once daily and do not exceed 10 mg once daily 1

Pediatric Patients:

• Ages 8 to <10 years with HeFH: 5-10 mg once daily 1
• Ages 10+ years with HeFH: 5-20 mg once daily 1
• Ages 7+ years with HoFH: 20 mg once daily 1

Clinical Context for High-Dose Use

• High-intensity statin therapy is defined as rosuvastatin 20-40 mg daily, achieving approximately 50-63% LDL-C reduction 4
• The 40 mg dose produces 63% LDL-C reduction compared to 52% with 10 mg 6
• Most patients achieve their LDL-C goals with rosuvastatin 10-20 mg daily; approximately 80% of at-risk patients reached target LDL-C levels with 10 mg in phase III trials 2

Safety Profile at Maximum Dose

• Myopathy incidence remains <0.1% at all recommended doses (5-40 mg daily) 4
• The incidence of proteinuria or microscopic hematuria is <1.5% with rosuvastatin 40 mg daily, mostly transient and not associated with progressive renal deterioration 7
• Elevations in creatine phosphokinase >10-fold the upper limit of normal occur in only 0.2-0.4% of patients at 5-40 mg daily 7

Critical Safety Warning

The 40 mg dose carries higher risk and should only be used when absolutely necessary for severe hypercholesterolemia. When drug interactions are present, the maximum safe dose may be substantially lower than 40 mg, and failure to adjust dosing appropriately can result in severe rhabdomyolysis 3, 1.