Simvastatin Dosing for Elevated LDL
For patients with elevated LDL requiring simvastatin, start with 20-40 mg once daily in the evening, but recognize that simvastatin is no longer a preferred agent for most patients needing significant LDL reduction. 1, 2
Current Simvastatin Dosing Guidelines
Standard Dosing
- The recommended dosage range is 20-40 mg once daily, taken in the evening 2
- The maximum recommended dose is 40 mg daily for new patients 2
- Simvastatin 80 mg is restricted only to patients already taking this dose chronically (≥12 months) without muscle toxicity 2
- The FDA explicitly prohibits initiating simvastatin 80 mg in new patients due to increased myopathy risk 1, 3, 2
Expected LDL Reduction by Dose
- Simvastatin 10 mg: <30% LDL reduction (low-intensity) 1
- Simvastatin 20-40 mg: 30-49% LDL reduction (moderate-intensity) 1
- Simvastatin 40 mg typically reduces LDL by approximately 35-41% 4, 5
Critical Limitation: Simvastatin Is Not High-Intensity Therapy
The most important consideration is that simvastatin at any approved dose (≤40 mg) cannot achieve high-intensity statin therapy (≥50% LDL reduction). 1 This is a major limitation because:
- Most patients with elevated LDL and cardiovascular disease require high-intensity statin therapy 1
- If your patient requires ≥50% LDL reduction or cannot achieve their LDL goal on simvastatin 40 mg, prescribe an alternative statin (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) 1, 2
Dose Modifications for Drug Interactions
Simvastatin has extensive CYP3A4-mediated drug interactions requiring dose restrictions 3, 2:
- With verapamil, diltiazem, or dronedarone: Maximum 10 mg daily 3, 2
- With amiodarone, amlodipine, or ranolazine: Maximum 20 mg daily 3, 2
- With lomitapide: Reduce dose by 50%, maximum 20 mg daily 2
For patients on these medications, strongly consider switching to atorvastatin or rosuvastatin, which have fewer drug interactions. 3
Dose Adjustments for Renal Impairment
- Severe renal impairment (CrCl 15-29 mL/min): Start with 5 mg daily 2
- No adjustment needed for mild-moderate renal impairment 2
Practical Dosing Algorithm
Step 1: Determine Intensity Needed
- High-risk patients (established ASCVD, diabetes with additional risk factors): Need high-intensity therapy → Do not use simvastatin; prescribe atorvastatin 40-80 mg or rosuvastatin 20-40 mg 1, 6, 3
- Moderate-risk patients: May use simvastatin 20-40 mg 1
Step 2: If Simvastatin Is Appropriate
- Start simvastatin 20 mg or 40 mg once daily in the evening 2
- Check lipid panel at 4-12 weeks 2
- If LDL goal not achieved on 40 mg: Switch to atorvastatin or rosuvastatin rather than attempting simvastatin 80 mg 1, 2
Step 3: Monitor for Safety
- Baseline ALT/AST and creatine kinase 3
- Reassess at 12 weeks, then annually 3
- Evaluate muscle symptoms at each visit 3
Common Pitfalls to Avoid
Do not initiate simvastatin 80 mg in any new patient—this is FDA-restricted due to myopathy risk 1, 3, 2
Do not use simvastatin as first-line in high-risk patients who need ≥50% LDL reduction—it cannot achieve high-intensity therapy at approved doses 1, 2
Do not ignore drug interactions—simvastatin has more interactions than atorvastatin or rosuvastatin due to CYP3A4 metabolism 3, 5
Do not continue simvastatin if inadequate response—switch to a more potent statin rather than adding multiple agents 1, 2
When Simvastatin Is Reasonable
Simvastatin 20-40 mg remains appropriate for:
- Moderate-risk primary prevention patients who need 30-40% LDL reduction 1
- Patients already stable on simvastatin 40 mg achieving their LDL goals 2
- Cost-sensitive situations where generic simvastatin provides adequate LDL reduction 5
However, for most patients with elevated LDL requiring significant reduction, atorvastatin or rosuvastatin are superior choices due to greater potency, fewer drug interactions, and ability to achieve high-intensity therapy. 1, 6, 3