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)06/2011
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)06/2011

Warnings and Precautions

Myopathy/Rhabdomyolysis (5.1) 06/2011
Liver Dysfunction (5.2) 06/2011

INDICATIONS AND USAGE

ZOCOR® 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 ApoB 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

ZOCOR has not been studied in Fredrickson Types I and V dyslipidemias. (1.4)

DOSAGE AND ADMINISTRATION

• Dose range is 5 to 40mg/day. (2.1)
• Recommended usual starting dose is 10 or 20mg once a day in the evening. (2.1)
• Recommended starting dose for patients at high risk of CHD is 40mg/day. (2.1)
• Due to the increased risk of myopathy, including rhabdomyolysis, use of the 80-mg dose of ZOCOR should be restricted to patients who have been taking simvastatin 80 mg chronically (e.g., for 12months or more) without evidence of muscle toxicity. (2.2)
• Patients who are currently tolerating the 80-mg dose of ZOCOR 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. (2.2)
• Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 80-mg dose of ZOCOR, patients unable to achieve their LDL-C goal utilizing the 40-mg dose of ZOCOR 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. (2.2)
• Adolescents (10-17 years of age) with HeFH: starting dose is 10mg/day; maximum recommended dose is 40 mg/day. (2.5)

DOSAGE FORMS AND STRENGTHS

Tablets: 5mg; 10mg; 20mg; 40mg; 80mg (3)

CONTRAINDICATIONS

• Concomitant administration of strong CYP3A4 inhibitors. (4, 5.1)
• Concomitant administration of gemfibrozil, cyclosporine, or danazol. (4, 5.1)
• 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

• Patients should be advised of the increased risk of myopathy including rhabdomyolysis with the 80-mg dose. (5.1)
• Skeletal muscle effects (e.g., myopathy and rhabdomyolysis): Risks increase with higher doses and concomitant use of certain medicines. Predisposing factors include advanced age (≥65), female gender, uncontrolled hypothyroidism, and renal impairment. (4, 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. (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 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

• Coumarin anticoagulants: Concomitant use with ZOCOR prolongs INR. Achieve stable INR prior to starting ZOCOR. Monitor INR frequently until stable upon initiation or alteration of ZOCOR therapy. (7.6)

USE IN SPECIFIC POPULATIONS

• Severe renal impairment: patients should be started at 5mg/day and be closely monitored. (2.6, 8.6)