Simvastatin

ZOCOR ® is indicated: To reduce the risk of total mortality by reducing risk of coronary heart disease death, non-fatal myocardial infarction and stroke, and the need for coronary and non-coronary revascularization procedures in adults with established coronary heart disease, cerebrovascular disease, peripheral vascular disease, and/or diabetes, who are at high risk of coronary heart disease events. As an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C): In adults with primary hyperlipidemia. In adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH). As an adjunct to other LDL-C-lowering therapies to reduce LDL-C in adults with homozygous familial hypercholesterolemia (HoFH). As an adjunct to diet for the treatment of adults with: Primary dysbetalipoproteinemia. Hypertriglyceridemia.

Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin acid and its metabolites are inhibitors of HMG-CoA reductase, the rate-limiting enzyme that converts HMG-CoA to mevalonate, a precursor of cholesterol.

Important Dosage and Administration Information: ZOCOR is no longer marketed in the 5 mg and 80 mg strengths. For dosing with the 5 mg strength, use another simvastatin product. Take ZOCOR orally once daily in the evening. Maximum recommended dosage is ZOCOR 40 mg once daily. An 80 mg daily dosage of ZOCOR is restricted to patients who have been taking simvastatin 80 mg daily chronically (e.g., for 12 months or more) without evidence of muscle toxicity. For patients that require a high-intensity statin or are unable to achieve their LDL-C goal receiving ZOCOR 40 mg daily, prescribe alternative LDL-C lowering treatment. Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating, and adjust the dosage if necessary. Adults: Recommended dosage is 20 mg to 40 mg once daily.

ZOCOR is contraindicated in the following conditions: Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone). Concomitant use of cyclosporine, danazol or gemfibrozil. Acute liver failure or decompensated cirrhosis. Hypersensitivity to simvastatin or any excipients in ZOCOR. Hypersensitivity reactions, including anaphylaxis, angioedema and Stevens-Johnson syndrome, have been reported. Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone). Hypersensitivity to simvastatin or any excipient in ZOCOR

Myopathy and Rhabdomyolysis: Risk factors include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher ZOCOR dosage. Chinese patients may be at higher risk for myopathy. Discontinue ZOCOR if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Temporarily discontinue ZOCOR in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis. Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing ZOCOR dosage. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Immune-Mediated Necrotizing Myopathy (IMNM): Rare reports of IMNM, an autoimmune myopathy, have been reported. Discontinue ZOCOR if IMNM is suspected.

The following important adverse reactions are described below and elsewhere in the labeling: Myopathy and Rhabdomyolysis Immune-Mediated Necrotizing Myopathy Hepatic Dysfunction Increases in HbA1c and Fasting Serum Glucose Levels Most common adverse reactions (incidence ≥5%) are upper respiratory infection, headache, abdominal pain, constipation, and nausea.

See full prescribing information for details regarding concomitant use of ZOCOR with other drugs or grapefruit juice that increase the risk of myopathy and rhabdomyolysis. Coumarin Anticoagulants: Obtain INR before ZOCOR initiation and monitor INR during ZOCOR dosage initiation or adjustment. Digoxin: During ZOCOR initiation, monitor digoxin levels.

Store between 41°F to 86°F (5°C to 30°C).