Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol (see National Cholesterol Education Program [NCEP] Treatment Guidelines, below).

In patients with CHD or at high risk of CHD, ZOCOR can be started simultaneously with diet.

Reductions in Risk of CHD Mortality and Cardiovascular Events

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, ZOCOR is 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.

Patients with Hypercholesterolemia Requiring Modifications of Lipid Profiles

ZOCOR is indicated to:

• Reduce elevated total-C, LDL-C, Apo B, and TG, and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson types IIa and IIb⁴).
• Treat patients with hypertriglyceridemia (Fredrickson type lV hyperlipidemia).
• Treat patients with primary dysbetalipoproteinemia (Fredrickson type lll hyperlipidemia).
• Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.

⁴Classification of Hyperlipoproteinemias.

Adolescent Patients with Heterozygous Familial Hypercholesterolemia (HeFH)

ZOCOR is 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, 10-17 years of age, with heterozygous familial hypercholesterolemia, if after an adequate trial of diet therapy the following findings are present:

1.    LDL cholesterol remains ≥ 190 mg/dL; or
2.    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.

General Recommendations

Prior to initiating therapy with simvastatin, secondary causes for hypercholesterolemia (e.g., hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism) should be excluded, and a lipid profile performed to measure total-C, HDL-C, and TG. For patients with TG less than 400 mg/dL (< 4.5 mmol/L), LDL-C can be estimated using the following equation:

LDL-C = total-C – [(0.20 x TG) + HDL-C]

For TG levels > 400 mg/dL (> 4.5 mmol/L), this equation is less accurate and LDL-C concentrations should be determined by ultracentrifugation. In many hypertriglyceridemic patients, LDL-C may be low or normal despite elevated total-C. In such cases, ZOCOR is not indicated.

Lipid determinations should be performed at intervals of no less than four weeks and dosage adjusted according to the patient's response to therapy.

The NCEP Treatment Guidelines are summarized in Table 6:

TABLE 6
NCEP Treatment Guidelines:
LDL-C Goals and Cutpoints for Therapeutic Lifestyle Changes
and Drug Therapy in Different Risk Categories

After the LDL-C goal has been achieved, if the TG is still ≥ 200 mg/dL, non-HDL-C (total-C minus HDL-C) becomes a secondary target of therapy. Non-HDL-C goals are set 30 mg/dL higher than LDL-C goals for each risk category.

At the time of hospitalization for an acute coronary event, consideration can be given to initiating drug therapy at discharge.

The NCEP classification of cholesterol levels in pediatric patients with a familial history of either hypercholesterolemia or premature cardiovascular disease is summarized in Table 7.

TABLE 7
NCEP Classification of Cholesterol Levels in Pediatric Patients
with a Familial History of Either HeFH or Premature CVD

Since the goal of treatment is to lower LDL-C, the NCEP recommends that LDL-C levels be used to initiate and assess treatment response. Only if LDL-C levels are not available, should the total-C be used to monitor therapy.

ZOCOR is indicated to reduce elevated LDL-C and TG levels in patients with Type IIb hyperlipidemia (where hypercholesterolemia is the major abnormality). However, it has not been studied in conditions where the major abnormality is elevation of chylomicrons (i.e., hyperlipidemia Fredrickson types I and V).⁴

The patient should be placed on a standard cholesterol-lowering diet. In patients with CHD or at high risk of CHD, ZOCOR can be started simultaneously with diet. The dosage should be individualized according to the goals of therapy and the patient's response. (For the treatment of adult dyslipidemia, see NCEP Treatment Guidelines. For the reduction in risks of major coronary events, see CLINICAL PHARMACOLOGY, Clinical Studies in Adults.) The dosage range is 5-80 mg/day (see below).

The recommended usual starting dose is 20 to 40 mg once a day in the evening. For patients at high risk for a CHD event due to existing coronary heart disease, 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. See below for dosage recommendations in special populations (i.e., homozygous familial hypercholesterolemia, adolescents and renal insufficiency) or for patients receiving concomitant therapy (i.e., cyclosporine, danazol, amiodarone, verapamil, or gemfibrozil).

Patients with Homozygous Familial Hypercholesterolemia

The recommended dosage for patients with homozygous familial hypercholesterolemia is ZOCOR 40 mg/day in the evening or 80 mg/day in 3 divided doses of 20 mg, 20 mg, and an evening dose of 40 mg. ZOCOR should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.

Adolescents (10-17 years of age) with Heterozygous Familial Hypercholesterolemia

The recommended usual starting dose is 10 mg once a day in the evening. The recommended dosing range is 10-40 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 Guidelines⁶ and CLINICAL PHARMACOLOGY). Adjustments should be made at intervals of 4 weeks or more.

Concomitant Lipid-Lowering Therapy

ZOCOR is effective alone or when used concomitantly with bile-acid sequestrants. If ZOCOR is used in combination with gemfibrozil, the dose of ZOCOR should not exceed 10 mg/day (see WARNINGS, Myopathy/Rhabdomyolysis and PRECAUTIONS, DRUG INTERACTIONS).

Patients taking Cyclosporine or Danazol

In patients taking cyclosporine or danazol concomitantly with ZOCOR (see WARNINGS, Myopathy/Rhabdomyolysis), therapy should begin with 5 mg/day and should not exceed 10 mg/day. Patients taking Amiodarone or Verapamil

In patients taking amiodarone or verapamil concomitantly with ZOCOR, the dose should not exceed 20 mg/day (see WARNINGS, Myopathy/Rhabdomyolysis and PRECAUTIONS, DRUG INTERACTIONS, Other drug interactions).

Patients with Renal Insufficiency

Because ZOCOR does not undergo significant renal excretion, modification of dosage should not be necessary in patients with mild to moderate renal insufficiency. However, caution should be exercised when ZOCOR is administered to patients with severe renal insufficiency; such patients should be started at 5 mg/day and be closely monitored (see CLINICAL PHARMACOLOGY, Pharmacokinetics and WARNINGS, Myopathy/Rhabdomyolysis).

No. 8360 — Tablets ZOCOR 5 mg are buff, oval, film-coated tablets, coded MSD 726 on one side and ZOCOR 5 on the other. They are supplied as follows:

NDC 0006-0726-31 unit of use bottles of 30
NDC 0006-0726-54 unit of use bottles of 90
NDC 0006-0726-82 bottles of 1000.

No. 8146 — Tablets ZOCOR 10 mg are peach, oval, film-coated tablets, coded MSD 735 on one side and plain on the other. They are supplied as follows:

NDC 0006-0735-31 unit of use bottles of 30
NDC 0006-0735-54 unit of use bottles of 90
NDC 0006-0735-82 bottles of 1000.

No. 8147 — Tablets ZOCOR 20 mg are tan, oval, film-coated tablets, coded MSD 740 on one side and plain on the other. They are supplied as follows:

NDC 0006-0740-31 unit of use bottles of 30
NDC 0006-0740-54 unit of use bottles of 90
NDC 0006-0740-82 bottles of 1000.

No. 8148 — Tablets ZOCOR 40 mg are brick red, oval, film-coated tablets, coded MSD 749 on one side and plain on the other. They are supplied as follows:

NDC 0006-0749-31 unit of use bottles of 30
NDC 0006-0749-54 unit of use bottles of 90
NDC 0006-0749-82 bottles of 1000.

No. 6577 — Tablets ZOCOR 80 mg are brick red, capsule-shaped, film-coated tablets, coded 543 on one side and 80 on the other. They are supplied as follows:

NDC 0006-0543-31 unit of use bottles of 30
NDC 0006-0543-54 unit of use bottles of 90
NDC 0006-0543-28 unit dose packages of 100
NDC 0006-0543-82 bottles of 1000. Storage

Store between 5-30°C (41-86°F).

⁶National Cholesterol Education Program (NCEP): Highlights of the Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Pediatrics. 89(3):495-501. 1992.
Manufactured for: MERCK & CO., INC.Whitehouse Station, NJ 08889, USA By: MERCK SHARP & DOHME LTD. Cramlington, Northumberland, UK NE23 3JU Issued August 2006
FDA Rev date: 6/1/2007

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