What is the recommended dose of Simvastatin (Zocor)?

From the Guidelines

Simvastatin should be initiated at a dose of 20-40 mg daily for moderate-intensity statin therapy, as recommended by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1.

Key Considerations for Simvastatin Dosing

• The dose of simvastatin can be adjusted based on the patient's response to therapy and tolerability, with a goal of achieving an LDL-C lowering of 30%–49% for moderate-intensity therapy 1.
• High-intensity statin therapy with simvastatin is not recommended due to the increased risk of myopathy, including rhabdomyolysis, associated with the 80 mg dose 1.
• Patients should be monitored for signs of myopathy, such as muscle pain, weakness, or tenderness, and liver function tests should be performed before starting therapy and as clinically indicated thereafter.

Special Populations

• Lower starting doses (10 mg) may be considered for patients who are at higher risk of myopathy or have renal impairment, although specific guidance on dosing in these populations is not provided in the referenced guideline 1.
• The evening dosing of simvastatin is recommended due to the enzyme HMG-CoA reductase being most active at night, which is responsible for cholesterol production in the liver.

From the FDA Drug Label

2.1 Important Dosage and Administration Information Take simvastatin tablets USP orally once daily in the evening. The maximum recommended dosage is simvastatin tablets USP 40 mg once daily [see DOSAGE AND ADMINISTRATION(2.2.3)]. 2.2 Recommended Dosage in Adult Patients The recommended dosage range of simvastatin tablets USP is 20 mg to 40 mg once daily 2.3 Recommended Dosage in Pediatric Patients 10 Years of Age and Older with HeFH The recommended dosage range of simvastatin tablets USP is 10 mg to 40 mg daily.

The recommended dosage range of simvastatin is:

• 20 mg to 40 mg once daily for adult patients
• 10 mg to 40 mg daily for pediatric patients 10 years of age and older with HeFH The maximum recommended dosage is 40 mg once daily, except for patients who have been taking simvastatin 80 mg daily chronically without evidence of muscle toxicity 2.

From the Research

Simvastatin Dose Efficacy

• The efficacy of simvastatin at a dose of 80 mg/day has been evaluated in several studies, with results indicating a significant advantage in LDL cholesterol-lowering effect compared to a dose of 40 mg/day 3, 4.
• A study published in 2000 found that simvastatin 80 mg/day produced greater reductions in LDL cholesterol, total cholesterol, and triglycerides compared to simvastatin 40 mg/day, with a mean percentage reduction from baseline in LDL cholesterol of 47% for the 80 mg group versus 41% for the 40 mg group 3.
• Another study published in 1998 found similar results, with simvastatin 80 mg/day providing substantial reductions in LDL cholesterol and allowing most patients to reach their NCEP target levels, with a mean percentage reduction from baseline in LDL cholesterol of 46% for the 80 mg group versus 38% for the 40 mg group 4.

Simvastatin Dose Safety

• The safety of simvastatin at a dose of 80 mg/day has also been evaluated, with results indicating that it is well tolerated, with close to 95% of patients completing the entire 48 weeks of treatment 3.
• A study published in 2000 found that myopathy and clinically significant hepatic transaminase increases occurred infrequently with both simvastatin 40 mg/day and 80 mg/day, with no significant difference between the groups in the number of patients with such increases 3.
• Another study published in 1998 found that simvastatin 80 mg/day had an excellent safety and tolerability profile, with only 2 patients (0.6%) developing myopathy and 6 patients (1.9%) experiencing consecutive, clinically significant hepatic transaminase elevations 4.

Comparison with Other Statins

• Simvastatin has been compared to other statins, such as atorvastatin and rosuvastatin, in terms of efficacy and safety, with results indicating that ezetimibe/simvastatin provides significantly greater improvements in key lipid parameters and higher attainment of LDL cholesterol targets than atorvastatin, with comparable tolerability 5.
• A study published in 2011 found that ezetimibe/simvastatin resulted in significantly greater reductions in LDL compared to rosuvastatin or atorvastatin, with a mean reduction of 37 mg/dL for ezetimibe/simvastatin versus 25 and 26 mg/dL for rosuvastatin and atorvastatin, respectively 6.