What is the recommended starting dose and dose titration of rosuvastatin in adults, and how should it be adjusted in patients with creatinine clearance less than 30 mL/min or severe hepatic impairment?

Rosuvastatin Dosing in Adults

Standard Starting Dose and Titration

For most adults without renal impairment, initiate rosuvastatin at 5-10 mg once daily for moderate-intensity therapy or 20-40 mg once daily for high-intensity therapy, depending on cardiovascular risk. 1

• Moderate-intensity rosuvastatin (5-10 mg daily) reduces LDL-C by 30-50% and is appropriate for patients with moderate cardiovascular risk 1
• High-intensity rosuvastatin (20-40 mg daily) reduces LDL-C by ≥50% and is recommended for patients with established heart disease or very high cardiovascular risk 1
• The 5 mg dose effectively reduces LDL-C by 42-52% in most patients, making it a reasonable starting point for many individuals 2, 3
• Reassess lipid levels as early as 4 weeks after initiation to guide dose titration 1

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Critical Dose Adjustments in Renal Impairment

Severe Renal Impairment (CrCl <30 mL/min, Not on Dialysis)

In patients with creatinine clearance <30 mL/min who are not on dialysis, initiate rosuvastatin at 5 mg once daily and do NOT exceed 10 mg daily. 1, 4, 5

• This represents the maximum safe dose in severe renal impairment, corresponding to moderate-intensity therapy only 1, 5
• High-intensity doses (20-40 mg) are contraindicated due to significantly increased risk of myopathy and other adverse effects 5
• Even patients with established coronary disease and severe renal impairment should not exceed 10 mg daily 1

Mild to Moderate Renal Impairment (CrCl ≥30 mL/min)

No dose adjustment is required for patients with CrCl ≥30 mL/min; standard dosing (5-40 mg) based on cardiovascular risk applies. 1, 4

• For patients with established heart disease and CrCl ≥30 mL/min, high-intensity therapy (20-40 mg) remains appropriate unless other contraindications exist 1

Dialysis Patients

Do NOT initiate rosuvastatin in patients already on hemodialysis, though continuation is reasonable if already established on therapy before dialysis began. 1, 4, 5

• If rosuvastatin is continued in dialysis patients, the dose should not exceed 10 mg daily 5
• Major trials (AURORA) showed no mortality or cardiovascular benefit from initiating statins in dialysis-dependent patients 4, 5

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Severe Hepatic Impairment

Rosuvastatin is contraindicated in patients with active liver disease or unexplained persistent elevations in hepatic transaminases. 6, 7

• While specific dosing guidance for hepatic impairment is limited in the evidence provided, the drug's hepatic metabolism necessitates extreme caution 6
• Monitor liver function tests before initiating therapy and as clinically indicated 7

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Special Population: Asian Patients

Asian patients require a lower starting dose of 5 mg daily regardless of renal function, due to approximately 2-fold higher plasma concentrations. 1, 7

• This applies to all patients of Asian ancestry, independent of other risk factors 7
• Dose escalation should proceed cautiously with close monitoring 7

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Practical Dosing Algorithm

1. Assess renal function (CrCl) and ethnicity first:

   • CrCl <30 mL/min (not on dialysis): Start 5 mg, max 10 mg daily 1, 5
   • CrCl ≥30 mL/min + Asian ancestry: Start 5 mg daily 1, 7
   • CrCl ≥30 mL/min + non-Asian: Proceed to step 2

2. Determine cardiovascular risk:

   • Established heart disease or very high risk: Start 20-40 mg daily (high-intensity) 1
   • Moderate risk or primary prevention: Start 5-10 mg daily (moderate-intensity) 1

3. Reassess at 4 weeks:

   • Check lipid panel and adjust dose if needed 1
   • Monitor for myopathy symptoms (muscle pain, weakness) 1, 7

4. Never exceed 10 mg daily in:

   • CrCl <30 mL/min 1, 5
   • Dialysis patients (if continuing therapy) 5
   • Patients on cyclosporine or protease inhibitors 7

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Common Pitfalls to Avoid

• Do not use high-intensity doses (20-40 mg) in severe renal impairment (CrCl <30 mL/min), as this dramatically increases myopathy risk 5
• Do not initiate rosuvastatin in patients already on dialysis, despite the temptation to treat elevated lipids—evidence shows no benefit 1, 4, 5
• Do not overlook Asian ancestry, which requires dose reduction independent of renal function 1, 7
• Do not combine with strong CYP3A4 inhibitors without caution, though rosuvastatin has favorable drug interaction profile compared to other statins 6, 7
• Monitor for myopathy risk factors: age >65 years, hypothyroidism, concomitant fibrates, or high doses 1, 7