Due to the increased risk of myopathy, including rhabdomyolysis, particularly during the first year of treatment, use of the 80-mg dose of simvastatin should be restricted to patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity. Patients unable to achieve their LDL-C goal utilizing the 40-mg dose of simvastatin should not be titrated to the 80 mg dose, but should be placed on alternative LDL-C lowering treatment(s) that provides greater LDL-C lowering.
The patient should be placed on a standard cholesterol lowering diet before receiving Simvastatin and should continue on this diet during treatment with Simvastatin. The recommended starting dose is 5-10 mg once a day in the evening. The recommended dosage range is 5-40mg/day as a single dose in the evening, the maximum recommended dose is 40mg/day. Prior to initiating therapy with Simvastatin, secondary causes for hypercholesterolemia (e.g. poorly controlled Diabetes Mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism) should be excluded and a lipid profile performed. Since the goal of treatment is to lower LDL-C, its levels should be used to initiate and assess treatment response. Only if LDL-C levels are not available, should the total-C be used to monitor therapy. Patients requiring reduction in LDL cholesterol of 20% or more to achieve their goal should be started on 10 mg/day of Simvastatin. A starting dose of 5 mg/day should be considered for patients requiring smaller reductions and for the elderly. Adjustment of dosage should be made at intervals of 4 weeks or more. Cholesterol levels should be monitored periodically and consideration should be given to reducing the dosage of Simvastatin if cholesterol falls significantly below the targeted range. In the elderly, maximum reductions in LDL cholesterol may be achieved with daily doses of 20 mg of Simvastatin or less. Because Simvastatin does not undergo significant renal excretion, modification of dosage should not be necessary in patients with mild to moderate renal insufficiency. However caution should be exercised when Simvastatin is administered to patients with severe renal insufficiency; such patients should be started at 5 mg/day and be closely monitored. Simvastatin is effective alone or when used concomitantly with bile-acid sequestrants. Use of Simvastatin with fibrate-type drugs such as Gemfibrozil or Clofibrate should be avoided. Dosage when taken with cyclosporine, gemfibrozil. In patients taking cyclosporine concomitantly, therapy should begin with 5 mg/day and should not exceed 10 mg/day.
In combination with Gemfibrozil or niacin, the dose of Simvastatin should not exceed 10 mg/day. In patients taking amiodarone or verapamil concomitantly, Simvastatin dose should not exceed 20 mg/day.