Posology : מינונים

2      DOSAGE AND ADMINISTRATION
2.1    Recommended Dosing
The usual dosage range is 5 to 40 mg/day. In patients with CHD, SIMOVIL can be started simultaneously with diet. The recommended usual starting dose is 10 or 20 mg once a day in the evening.
Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter.
2.2 Restricted Dosing for 80 mg
Due to the increased risk of myopathy, including rhabdomyolysis, particularly during the first year of treatment, use of the 80-mg dose of SIMOVIL 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 [see Warnings and Precautions (5.1)].
Patients who are currently tolerating the 80-mg dose of SIMOVIL who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin with less potential for the drug-drug interaction.
Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 80-mg dose of SIMOVIL, patients unable to achieve their LDL-C goal utilizing the 40-mg dose of SIMOVIL 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.
2.3 Coadministration with Other Drugs
Patients taking Verapamil, Diltiazem or Dronedarone
• The dose of SIMOVIL should not exceed 10 mg/day [see Warnings and Precautions (5.1), Drug Interactions (7.4), and Clinical Pharmacology (12.3)].
Patients taking Amiodarone, Amlodipine or Ranolazine
• The dose of SIMOVIL should not exceed 20 mg/day [see Warnings and Precautions (5.1), Drug Interactions (7.4), and Clinical Pharmacology (12.3)].
Patients taking Bile Acid Sequestrants
• SIMOVIL is effective alone or in combination with bile acid sequestrants. Dosing should occur either > 2 hours before or > 4 hours after administration of a bile acid sequestrant.
2.4     Patients with Homozygous Familial Hypercholesterolemia
The recommended dosage is 40 mg/day in the evening [see Dosage and Administration, Restricted Dosing for 80 mg (2.2)]. SIMOVIL should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.
Simvastatin exposure is approximately doubled with concomitant use of lomitapide; therefore, the dose of SIMOVIL should be reduced by 50% if initiating lomitapide. SIMOVIL dosage should not exceed 20 mg/day (or 40 mg/day for patients who have previously taken SIMOVIL 80 mg/day chronically, e.g., for
12 months or more, without evidence of muscle toxicity) while taking lomitapide.
2.6 Patients with Renal Impairment
Because SIMOVIL does not undergo significant renal excretion, modification of dosage should not be necessary in patients with mild to moderate renal impairment. However, caution should be exercised when SIMOVIL is administered to patients with severe renal impairment; such patients should be started at 5 mg/day and be closely monitored [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].
2.7 Chinese Patients Taking Lipid-Modifying Doses (≥1 g/day Niacin) of Niacin-Containing
Products
Because of an increased risk for myopathy in Chinese patients taking simvastatin 40 mg coadministered with lipid-modifying doses (≥1 g/day niacin) of niacin-containing products, caution should be used when treating Chinese patients with simvastatin doses exceeding 20 mg/day coadministered with lipid-modifying doses of niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of niacin-containing products. The cause of the increased risk of myopathy is not known. It is also unknown if the risk for myopathy with coadministration of simvastatin with lipid-modifying doses of niacin-containing products observed in Chinese patients applies to other Asian patients. [See Warnings and Precautions (5.1).]