What dose of Crestor (rosuvastatin) is considered an overdose?

Rosuvastatin (Crestor) Overdose: Defining Toxic Doses

Rosuvastatin doses exceeding 40 mg daily should be considered an overdose, as this is the maximum FDA-approved dose, with doses of 5-40 mg being the recommended therapeutic range. 1

Understanding Rosuvastatin Dosing

Rosuvastatin (Crestor) is a potent HMG-CoA reductase inhibitor (statin) with the following standard dosing parameters:

• Standard therapeutic range: 5-40 mg once daily 1
• High-intensity therapy: 20-40 mg daily (achieves ≥50% LDL-C reduction) 1, 2
• Moderate-intensity therapy: 5-10 mg daily (achieves 30-49% LDL-C reduction) 1

Dose Adjustments for Special Populations

Certain patient populations require dose limitations that would make lower doses potentially toxic:

• Severe renal impairment (CrCl <30 mL/min):

  • Maximum dose: 10 mg daily
  • Starting dose: 5 mg daily 1

• Patients taking cyclosporine, tacrolimus, everolimus, or sirolimus:

  • Maximum dose: 5 mg daily 1
  • Exceeding this limit significantly increases risk of rhabdomyolysis 1

Signs and Symptoms of Rosuvastatin Toxicity

Overdose manifestations typically involve exaggerated versions of known adverse effects:

• Muscle-related toxicity: Myalgia, myopathy, rhabdomyolysis (most serious)
• Laboratory abnormalities: Elevated creatine phosphokinase (CPK) >10× upper limit of normal
• Other symptoms: Gastrointestinal disturbances, liver enzyme elevations, proteinuria

Risk Factors for Toxicity at Lower Doses

Certain factors may make standard doses potentially toxic:

1. Drug interactions: Particularly with cyclosporine (7-fold increase in rosuvastatin AUC) 1
2. Renal impairment: Rosuvastatin clearance is reduced in severe renal disease 1
3. Age: While age alone doesn't significantly alter pharmacokinetics (only 6% higher AUC in young vs. elderly), older patients may have reduced renal function 3
4. Gender: Women have slightly higher exposure (9% higher AUC) than men, but this isn't considered clinically significant enough to warrant dose adjustment 3

Management Algorithm for Suspected Overdose

1. Assess for symptoms: Muscle pain/weakness, dark urine, kidney dysfunction

2. Laboratory evaluation:

   • CPK levels (marker of muscle damage)
   • Renal function (BUN, creatinine)
   • Liver function tests
   • Urinalysis (check for myoglobinuria)

3. Management:

   • Discontinue rosuvastatin immediately
   • Provide supportive care
   • Hydration to protect kidneys if rhabdomyolysis is present
   • Monitor renal function closely

Clinical Pearls

• Rosuvastatin is more potent on a milligram-per-milligram basis than most other statins, achieving 42-49% LDL-C reduction at just 5-10 mg doses 4
• Unlike some statins, rosuvastatin is not significantly metabolized by CYP3A4, reducing some drug interaction risks 5
• Rosuvastatin may actually improve renal function parameters in some patients during long-term therapy 6

Common Pitfalls to Avoid

• Failure to adjust dose in renal impairment: Always check renal function before prescribing
• Missing drug interactions: Particularly immunosuppressants that dramatically increase rosuvastatin levels
• Overlooking early signs of toxicity: Muscle pain, weakness, or dark urine should prompt immediate evaluation

Remember that any dose exceeding the FDA-approved maximum of 40 mg daily should be considered an overdose, and doses should be further limited in patients with renal impairment or taking interacting medications.