Zocor

Zocor Information

Brand Name: Zocor

Generic Name: Simvastatin, Simbastatine

Other Common Names: Simvastatina

Zocor (simvastatin) is a lipid lowering drug. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol. 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.

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:

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

Since the goal of Zocor 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 Zocor 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, Zocor has not been studied in conditions where the major abnormality is elevation of chylomicrons (i.e., hyperlipidemia Fredrickson types I and V).

Zocor Ingredients and Composition

How Does Zocor Work?

The involvement of low-density lipoprotein cholesterol (LDL-C) in atherogenesis has been well-documented in clinical and pathological studies, as well as in many animal experiments. Epidemiological studies have established that elevated plasma levels of total cholesterol (total-C), LDL-C, and apolipoprotein B (Apo B) promote human atherosclerosis and are risk factors for developing cardiovascular disease, while increased levels of high-density lipoprotein cholesterol (HDL-C) and its transport complex, Apo A-I, are associated with decreased cardiovascular risk. High plasma triglycerides (TG) and cholesterol-enriched TG-rich lipoproteins, including very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and remnants, can also promote atherosclerosis. Elevated plasma TG are frequently found in a triad with low HDL-C and small LDL particles, as well as in association with non-lipid metabolic risk factors for CHD. As such, total plasma TG has not consistently been shown to be an independent risk factor for CHD. Furthermore, the independent effect of raising HDL-C or lowering TG on the risk of coronary and cardiovascular morbidity and mortality has not been determined.

In the Scandinavian Simvastatin Survival Study (4S), the effect of improving lipoprotein levels with Zocor on total mortality was assessed in 4,444 patients with CHD and baseline total cholesterol (total-C) 212-309 mg/dL (5.5-8.0 mmol/L). The patients were followed for a median of 5.4 years. In this multicenter, randomized, double-blind, placebo-controlled study, Zocor significantly reduced the risk of mortality by 30% (11.5% vs 8.2%, placebo vs Zocor); of CHD mortality by 42% (8.5% vs 5.0%); and of having a hospital-verified non-fatal myocardial infarction by 37% (19.6% vs 12.9%). Furthermore, Zocor significantly reduced the risk for undergoing myocardial revascularization procedures (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) by 37% (17.2% vs 11.4%).

Zocor has been shown to reduce both normal and elevated LDL-C concentrations. LDL is formed from very-low-density lipoprotein (VLDL) and is catabolized predominantly by the high-affinity LDL receptor. The mechanism of the LDL-lowering effect of Zocor may involve both reduction of VLDL cholesterol concentration, and induction of the LDL receptor, leading to reduced production and/or increased catabolism of LDL-C. Apo B also falls substantially during treatment with Zocor. As each LDL particle contains one molecule of Apo B, and since in patients with predominant elevations in LDL-C (without accompanying elevation in VLDL) little Apo B is found in other lipoproteins, this strongly suggests that Zocor does not merely cause cholesterol to be lost from LDL, but also reduces the concentration of circulating LDL particles. In addition, Zocor reduces VLDL and TG and increases HDL-C. The effects of Zocor on Lp(a), fibrinogen, and certain other independent biochemical risk markers for CHD are unknown.

Zocor is a specific inhibitor of HMG-CoA reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate. The conversion of HMG-CoA to mevalonate is an early step in the biosynthetic pathway for cholesterol.

How To Take Zocor and Zocor Dosage and Administration

Before starting their Zocor dosage, patients 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. The Zocor dosage range is 5-80 mg/day (see below).

The recommended usual starting Zocor 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 Zocor dosage recommendations in special populations (i.e., homozygous familial hypercholesterolemia, adolescents and renal insufficiency) or for patients receiving concomitant therapy (i.e., cyclosporine, amiodarone, verapamil, fibrates or niacin).

Patients with Homozygous Familial Hypercholesterolemia

The recommended Zocor dosage for patients with homozygous familial hypercholesterolemia is 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 Zocor dose is 10 mg once a day in the evening. The recommended dosing range is 10-40 mg/day; the maximum recommended Zocor dose is 40 mg/day. Doses should be individualized according to the recommended goal of therapy. 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, other fibrates or lipid-lowering doses (<1 g/day) of niacin, the dose of Zocor should not exceed 10 mg/day.

Patients taking Cyclosporine

In patients taking cyclosporine concomitantly with Zocor, 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.

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

If you suspect a Zocor Overdose

Significant lethality was observed in mice after a single oral Zocor dose of 9 g/m2. No evidence of lethality was observed in rats or dogs treated with Zocor doses of 30 and 100 g/m2, respectively. No specific diagnostic signs were observed in rodents. At these doses the only signs seen in dogs were emesis and mucoid stools.

A few cases of overdosage with Zocor have been reported; no patients had any specific symptoms, and all patients recovered without sequelae. The maximum dose taken was 450 mg. Until further experience is obtained, no specific treatment of overdosage with Zocor can be recommended.

The dialyzability of simvastatin and its metabolites in man is not known at present.

Zocor Side Effects

Zocor Warnings

Zocor Precautions and Contraindications

General

Zocor (simvastatin) may cause elevation of CK and transaminase levels This should be considered in the differential diagnosis of chest pain in a patient on therapy with Zocor.

Zocor Contraindications

Active liver disease or unexplained persistent elevations of serum transaminases are contraindicated with Zocor. Pregnancy and lactation are contraindicated with Zocor. 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. Moreover, cholesterol and other products of the cholesterol biosynthesis pathway are essential components for fetal development, including synthesis of steroids and cell membranes. Because of the ability of inhibitors of HMG-CoA reductase such as Zocor to decrease the synthesis of cholesterol and possibly other products of the cholesterol biosynthesis pathway, Zocor is contraindicated during pregnancy and in nursing mothers. Zocor 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, Zocor should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus.

Taking Zocor during Pregnancy or Breast-feeding

Because of the ability of inhibitors of HMG-CoA reductase such as Zocor to decrease the synthesis of cholesterol and possibly other products of the cholesterol biosynthesis pathway, Zocor is contraindicated during pregnancy and in nursing mothers. Zocor 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, Zocor should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus.

Zocor and Alcohol Interaction

The drug should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease. Active liver diseases or unexplained transaminase elevations are contraindications to the use of Zocor (simvastatin).

Zocor Clinical Trials and Studies

Storing Zocor

Store Zocor between 5-30°C (41-86°F).

Additional Patient Information for Zocor

Patients should be advised about substances they should not take concomitantly with Zocor (simvastatin) and be advised to report promptly unexplained muscle pain, tenderness, or weakness. Patients should also be advised to inform other physicians prescribing a new medication that they are taking Zocor.

Information about the Manufacturer of Zocor

Tablets Zocor (simvastatin) 5 mg, 10 mg, 20 mg, 40 mg and 80 mg are manufactured by:

MERCK SHARP & DOHME LTD, Cramlington, Northumberland, UK NE23 3JU