Maximum Daily Dose of Simvastatin
The maximum recommended daily dose of simvastatin is 40 mg once daily for most patients, with the 80 mg dose restricted only to patients who have been taking it chronically for ≥12 months without muscle toxicity. 1
FDA-Mandated Dose Restrictions
The FDA issued a safety announcement in June 2011 that fundamentally changed simvastatin dosing due to increased myopathy risk at higher doses:
- Simvastatin 80 mg should NOT be started in new patients, including those already taking lower doses 2, 1
- The 80 mg dose is restricted exclusively to patients who have been taking this dose chronically (e.g., for 12 months or more) without evidence of muscle toxicity 1
- For patients requiring high-intensity statin therapy or unable to achieve LDL-C goals on simvastatin 40 mg daily, prescribe alternative LDL-C-lowering treatment rather than increasing to 80 mg 1
Standard Dosing Recommendations
- The recommended dosage range for adult patients is 20 mg to 40 mg once daily 1
- For pediatric patients ≥10 years with heterozygous familial hypercholesterolemia, the range is 10 mg to 40 mg daily 1
- Simvastatin should be taken once daily in the evening 1
Dose Modifications for Drug Interactions
Certain concomitant medications require strict dose limitations due to increased myopathy risk:
- With verapamil, diltiazem, or dronedarone: Do not exceed 10 mg daily 3, 1
- With amiodarone, amlodipine, or ranolazine: Do not exceed 20 mg daily 3, 1
- With lomitapide: Reduce simvastatin dose by 50%, not exceeding 20 mg daily (or 40 mg for chronic 80 mg users) 1
- Simvastatin is contraindicated with concurrent cyclosporine or gemfibrozil use 2
Special Population Considerations
Severe Renal Impairment:
- For patients with creatinine clearance 15-29 mL/min, the recommended starting dose is 5 mg once daily 2, 1
- No dosage adjustments needed for mild to moderate renal impairment 1
Alternative High-Intensity Statin Options
When patients require >50% LDL-C reduction or cannot achieve goals on simvastatin 40 mg:
- Switch to atorvastatin 40-80 mg or rosuvastatin 20-40 mg (high-intensity statins) rather than increasing simvastatin dose 3, 4
- These alternatives have fewer drug interactions and better safety profiles at higher doses 3
- Atorvastatin and rosuvastatin are not primarily metabolized by CYP3A4, reducing interaction risk 3
Clinical Context
The restriction on simvastatin 80 mg reflects evidence that the risk-benefit ratio becomes unfavorable at this dose, with significantly increased myopathy risk compared to lower doses 2, 3. Historical studies showed simvastatin 80 mg produced 47% LDL-C reduction versus 41% with 40 mg 5, but the modest additional benefit does not justify the elevated safety risk in contemporary practice.