SIMVASTATIN — simvastatin tablet, film coated
Lupin Pharmaceuticals, Inc.
Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. In patients with coronary heart disease (CHD) or at high risk of CHD, simvastatin tablets USP can be started simultaneously with diet.
In patients at high risk of coronary events because of existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, simvastatin tablets USP are indicated to:
- Reduce the risk of total mortality by reducing CHD deaths.
- Reduce the risk of non-fatal myocardial infarction and stroke.
- Reduce the need for coronary and non-coronary revascularization procedures.
- Reduce elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary hyperlipidemia (Fredrickson type IIa, heterozygous familial and nonfamilial) or mixed dyslipidemia (Fredrickson type IIb).
- Reduce elevated TG in patients with hypertriglyceridemia (Fredrickson type lV hyperlipidemia).
- Reduce elevated TG and VLDL-C in patients with primary dysbetalipoproteinemia (Fredrickson type III hyperlipidemia).
- Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH) as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.
Simvastatin tablets USP are indicated as an adjunct to diet to reduce total-C, LDL-C, and Apo B levels in adolescent boys and girls who are at least one year post-menarche, 10 to 17 years of age, with HeFH, if after an adequate trial of diet therapy the following findings are present:
- LDL cholesterol remains ≥190 mg/dL; or
- LDL cholesterol remains ≥160 mg/dL and
- There is a positive family history of premature cardiovascular disease (CVD) or
- Two or more other CVD risk factors are present in the adolescent patient.
The minimum goal of treatment in pediatric and adolescent patients is to achieve a mean LDL-C <130 mg/dL. The optimal age at which to initiate lipid-lowering therapy to decrease the risk of symptomatic adulthood CAD has not been determined.
The usual dosage range is 5 to 40 mg/day. In patients with CHD or at high risk of CHD, simvastatin tablets USP can be started simultaneously with diet. The recommended usual starting dose is 10 or 20 mg once a day in the evening. For patients at high risk for a CHD event due to existing CHD, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, the recommended starting dose is 40 mg/day. Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter.
Due to the increased risk of myopathy, including rhabdomyolysis, particularly during the first year of treatment, use of the 80-mg dose of simvastatin tablets USP 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 simvastatin tablets USP 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 simvastatin tablets USP, patients unable to achieve their LDL-C goal utilizing the 40-mg dose of simvastatin tablets USP 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 dose of simvastatin tablets USP should not exceed 10 mg/day [see WARNINGS AND PRECAUTIONS (5.1), DRUG INTERACTIONS (7.3),and CLINICAL PHARMACOLOGY (12.3)].
- The dose of simvastatin tablets USP should not exceed 20 mg/day [see WARNINGS AND PRECAUTIONS (5.1), DRUG INTERACTIONS (7.3),and CLINICAL PHARMACOLOGY (12.3)].
The recommended dosage is 40 mg/day in the evening [see DOSAGE AND ADMINISTRATION, Restricted Dosing for 80 mg (2.2)]. Simvastatin tablets USP 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 simvastatin tablets USP should be reduced by 50% if initiating lomitapide. Simvastatin tablets USP dosage should not exceed 20 mg/day (or 40 mg/day for patients who have previously taken simvastatin tablets USP 80 mg/day chronically, e.g., for 12 months or more, without evidence of muscle toxicity) while taking lomitapide.
The recommended usual starting dose is 10 mg once a day in the evening. The recommended dosing range is 10 to 40 mg/day; the maximum recommended dose is 40 mg/day. Doses should be individualized according to the recommended goal of therapy [see NCEP Pediatric Panel Guidelines1 and CLINICAL STUDIES (14.2)]. Adjustments should be made at intervals of 4 weeks or more.
Because simvastatin tablets USP do 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 simvastatin tablets USP are 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)].
- Simvastatin tablets 5 mg are tan colored, round, biconvex, film-coated tablets debossed with ‘LL’ on one side and ‘C01’ on the other side.
- Simvastatin tablets 10 mg are peach colored, oval shaped, biconvex, film-coated tablets debossed with ‘LL’ on one side and ‘C02’ on the other side.
- Simvastatin tablets 20 mg are tan colored, oval shaped, biconvex, film-coated tablets debossed with ‘LL’ on one side and ‘C03’ on the other side.
- Simvastatin tablets 40 mg are brick red colored, round shaped, biconvex, film-coated tablets debossed with ‘LL’on one side and ‘C04’ on the other side.
- Simvastatin tablets 80 mg are brick red colored, capsule shaped, biconvex, film-coated tablets debossed with ‘LL’on one side and ‘C05’ on the other side.
- Concomitant administration of strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, and cobicistat-containing products) [see WARNINGS AND PRECAUTIONS (5.1)].
- Concomitant administration of gemfibrozil, cyclosporine, or danazol [see WARNINGS AND PRECAUTIONS (5.1)].
- Hypersensitivity to any component of this medication [see ADVERSE REACTIONS (6.2)].
- Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels [see WARNINGS AND PRECAUTIONS (5.3)].
- Women who are pregnant or may become pregnant. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Because HMG-CoA reductase inhibitors (statins) decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, simvastatin may cause fetal harm when administered to a pregnant woman. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. There are no adequate and well-controlled studies of use with simvastatin during pregnancy; however, in rare reports congenital anomalies were observed following intrauterine exposure to statins. In rat and rabbit animal reproduction studies, simvastatin revealed no evidence of teratogenicity. Simvastatin should be administered to women of childbearing age only when such patients are highly unlikely to conceive. If the patient becomes pregnant while taking this drug, simvastatin should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus [see USE IN SPECIFIC POPULATIONS (8.1)].
- Nursing mothers. It is not known whether simvastatin is excreted into human milk; however, a small amount of another drug in this class does pass into breast milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require treatment with simvastatin should not breastfeed their infants [see USE IN SPECIFIC POPULATIONS (8.3)].
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