HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use simvastatin safely and effectively. See full prescribing information for simvastatin.
Simvastatin Tablets USP
Initial U.S. Approval: 1991
RECENT MAJOR CHANGES
Dosage and Administration
Recommended Dosing (2.1) 06/2011
Restricted Dosing for 80 mg (2.2) 06/2011
Coadministration with Other Drugs (2.3) 10/2011
Patients with Homozygous Familial Hypercholesterolemia (2.4) 06/2011
Chinese Patients Taking Lipid-Modifying Doses (≥1 g/day Niacin) of Niacin-Containing Products (2.7) 06/2011
Contraindications (4) 02/2012
Warnings and Precautions
Myopathy/Rhabdomyolysis (5.1) 02/2012
Liver Dysfunction (5.2) 10/2011
Endocrine Function (5.3) 10/2011
INDICATIONS AND USAGE
Simvastatin is an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to:
-
Reduce the risk of total mortality by reducing CHD deaths and reduce the risk of non-fatal myocardial infarction, stroke, and the need for revascularization procedures in patients at high risk of coronary events. (1.1)
-
Reduce elevated total-C, LDL-C, Apo B, TG and increase HDL-C in patients with primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia. (1.2)
-
Reduce elevated TG in patients with hypertriglyceridemia and reduce TG and VLDL-C in patients with primary dysbetalipoproteinemia. (1.2)
-
Reduce total-C and LDL-C in adult patients with homozygous familial hypercholesterolemia. (1.2)
-
Reduce elevated total-C, LDL-C, and Apo B in boys and postmenarchal girls, 10 to 17 years of age with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy. (1.2, 1.3)
Limitations of Use
Simvastatin has not been studied in Fredrickson Types I and V dyslipidemias. (1.4)
DOSAGE AND ADMINISTRATION
-
Dose range is 5-80 mg/day. (2.1)
-
Recommended usual starting dose is 20-40 mg once a day in the evening. (2.1)
-
Recommended starting dose for patients at high risk of CHD is 40 mg/day. (2.1)
-
Adolescents (10-17 years of age) with HeFH: starting dose is 10 mg/day; maximum recommended dose is 40 mg/day. (2.3)
DOSAGE FORMS AND STRENGTHS
Tablets: 5 mg; 10 mg; 20 mg; 40 mg; 80 mg (3)
CONTRAINDICATIONS
-
Hypersensitivity to any component of this medication. (4, 6.2)
-
Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels. (4, 5.2)
-
Women who are pregnant or may become pregnant. (4, 8.1)
-
Nursing mothers. (4, 8.3)
WARNINGS AND PRECAUTIONS
-
Skeletal muscle effects (e.g., myopathy and rhabdomyolysis): Risks increase with higher doses and concomitant use of certain CYP3A4 inhibitors, gemfibrozil, cyclosporine, danazol, amiodarone, and verapamil and diltiazem. Predisposing factors include advanced age (≥65), uncontrolled hypothyroidism, and renal impairment. (5.1, 8.5, 8.6)
-
Patients should be advised to report promptly any symptoms of myopathy. Simvastatin therapy should be discontinued immediately if myopathy is diagnosed or suspected. See Drug Interaction table. (5.1)
-
Liver enzyme abnormalities and monitoring: Persistent elevations in hepatic transaminase can occur. Monitor liver enzymes before and during treatment. Patients titrated to the 80-mg dose should receive more frequent liver function tests than patients on lower doses. (5.2)
ADVERSE REACTIONS
Most common adverse reactions (incidence ≥5.0%) are: upper respiratory infection, headache, abdominal pain, constipation, and nausea. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
DRUG INTERACTIONS
Drug Interactions Associated with Increased Risk of Myopathy/Rhabdomyolysis (2.6, 5.1, 7.1, 7.2, 7.3, 7.4)
|
Interacting Agents |
Prescribing Recommendations |
|
Itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone |
Avoid simvastatin |
|
Gemfibrozil, cyclosporine, danazol |
Do not exceed 10 mg simvastatin daily |
|
Amiodarone, verapamil |
Do not exceed 20 mg simvastatin daily |
|
Diltiazem |
Do not exceed 40 mg simvastatin daily |
|
Grapefruit juice |
Avoid large quantities of grapefruit juice (>1 quart daily) |
-
Coumarin anticoagulants: Concomitant use with simvastatin prolongs INR. Achieve stable INR prior to starting simvastatin. Monitor INR frequently until stable upon initiation or alteration of simvastatin therapy. (7.7)
USE IN SPECIFIC POPULATIONS
-
Severe renal impairment: patients should be started at 5 mg/day and be closely monitored. (2.4, 8.6)
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 8/2013
FULL PRESCRIBING INFORMATION: CONTENTS*
|
