Atocor (atorvastatin) coated tablets 20 mg. №30

Description

Ingredients

active ingredient: atorvastatin;

1 film-coated tablet contains atorvastatin calcium trihydrate equivalent to atorvastatin 10 mg or 20 mg

Excipients: microcrystalline cellulose, mannitol (E 421), sodium starch (type A), meglumine, poloxamer, hydroxypropyl cellulose, magnesium stearate, Opadry white dye 03H18479 (titanium dioxide (E 171), hypromellose, propylene glycol, talc).

Dosage form

Film-coated tablets.

White or off-white, triangular, biconvex, film-coated tablets, debossed “A” on one side and debossed “10” or “20” on the other side of the tablet.

Pharmacotherapeutic group

hypolipidemic agents. HMG CoA reductase inhibitors. ATX code C10A A05.

pharmachologic effect

Atocor is a synthetic lipid-lowering drug. Atorvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, an early step in cholesterol biosynthesis that limits the rate of its formation.

Atorvastatin is a selective competitive inhibitor of HMG-CoA reductase, an enzyme that determines the rate of conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. Cholesterol and triglycerides circulate in the bloodstream in combination with lipoproteins. These complexes are separated by ultracentrifugation into HDL (high density lipoprotein), LDLP (intermediate density lipoprotein), LDL (low density lipoprotein) and VLDL (very low density lipoprotein) fractions. Triglycerides (TG) and cholesterol in the liver are incorporated into VLDL and released into the blood plasma for transport to peripheral tissues. LDL is formed by VLDL and catabolized by interaction with high-affinity LDL receptors.

In animal models, atorvastatin lowers plasma cholesterol and lipoprotein levels by inhibiting hepatic HMG-CoA reductase and cholesterol synthesis and by increasing hepatic LDL receptors on cell surfaces to enhance LDL uptake and catabolism; atorvastatin also reduces the production of LDL and the number of these particles. Atorvastatin lowers LDL cholesterol levels in some patients with homozygous familial hypercholesterolemia, a group of people who rarely respond to treatment with other lipid-lowering drugs.

Numerous clinical studies have shown that elevated levels of total cholesterol, LDL cholesterol and apo B (membrane complex for LDL cholesterol) provoke the development of atherosclerosis. Similarly, reduced levels of HDL cholesterol (and its transport complex – a by A) are associated with the development of atherosclerosis. Epidemiological studies have established that cardiovascular morbidity and mortality vary in direct proportion to the level of total cholesterol and LDL cholesterol and inversely with the level of HDL cholesterol.

Atorvastatin reduces total cholesterol, LDL cholesterol and apo B in patients with homozygous and heterozygous familial hypercholesterolemia, non-familial forms of hypercholesterolemia and mixed dyslipidemia. Atorvastatin also lowers VLDL and TG cholesterol levels, and also causes an unsustainable increase in HDL cholesterol and apolipoprotein A-1. Atorvastatin lowers total cholesterol, LDL cholesterol, VLDL cholesterol, apo B, triglycerides and HDL-C, and increases HDL cholesterol in patients with isolated hypertriglyceridemia. Atorvastatin reduces LDL-C in patients with dysbetalipoproteinemia.

Like LDL, lipoproteins rich in cholesterol and triglycerides, including VLDL, LDL and residues, can also contribute to the development of atherosclerosis. Elevated plasma triglyceride levels are often found in the triad of low HDL cholesterol and small LDL lobules, and in association with non-lipid metabolic risk factors for coronary artery disease. Total plasma triglycerides per se have not been consistently shown to be an independent risk factor for the development of coronary artery disease. In addition, an increase in HDL or a decrease in triglycerides has been found to have an independent effect on the risk of coronary and cardiovascular morbidity and mortality.

Atorvastatin, as well as some of its metabolites, are pharmacologically active in humans. The main site of action of atorvastatin is the liver, which plays a major role in cholesterol synthesis and LDL clearance. The dose of the drug, in contrast to the systemic concentration of the drug, better correlates with a decrease in LDL cholesterol. Individual dose selection should be carried out depending on the therapeutic response.

Indications

Prevention of cardiovascular disease in adults.

For adult patients without symptomatic coronary heart disease but with multiple risk factors for coronary heart disease such as age, smoking, hypertension, low HDL, or a family history of early coronary artery disease, Atocor (atorvastatin) 20 mg. is indicated for:

• reducing the risk of myocardial infarction
• reducing the risk of stroke;
• reducing the risk of revascularization procedures and angina pectoris.

For adult patients with type II diabetes mellitus and without symptomatic coronary heart disease, but with several risk factors for coronary heart disease, such as retinopathy, albuminuria, smoking or arterial hypertension, Atocor is indicated for:

• reducing the risk of myocardial infarction
• reducing the risk of stroke.

For adult patients with clinically significant ischemic heart disease, Atocor is indicated for:

• reduced risk of non-fatal myocardial infarction
• reducing the risk of fatal and non-fatal stroke;
• reducing the risk of revascularization procedures;
• reduced risk of hospitalization due to congestive heart failure
• reducing the risk of angina pectoris.

Hyperlipidemia.

In adult patients.

• As an adjunct to diet to reduce elevated levels of total cholesterol, LDL cholesterol, apolipoprotein B and triglycerides, and to increase HDL cholesterol levels in patients with primary hypercholesterolemia (heterozygous familial and non-familial) and mixed dyslipidemia (Fredrickson classification types IIa and IIb) ) .
• As an adjunct to diet for the treatment of patients with elevated serum triglyceride levels (Fredrickson type IV).
• For the treatment of patients with primary dysbetalipoproteinemia (Fredrickson type III) in cases where dietary compliance is not effective enough.
• To reduce total cholesterol and LDL cholesterol in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering therapies (eg LDL apheresis), or when such treatments are not available.

In children.

• As an adjunct to a diet to reduce total cholesterol, LDL cholesterol, and apolipoprotein B in boys and girls after the onset of menstruation between the ages of 10 and 17 with heterozygous familial hypercholesterolemia, if, after appropriate dietary therapy, the test results are:

a) LDL cholesterol remains ≥ 190 mg/dl (≥ 4.91 mmol/l) or

b) LDL cholesterol ≥ 160 mg/dl (≥ 4.14 mmol/l) and:

• family history of early cardiovascular disease or
• two or more other risk factors for cardiovascular disease are present in a pediatric patient.

Contraindications

• Active liver disease, which may include a persistent increase in liver transaminases of unknown etiology.
• Hypersensitivity to any of the components of Atocor (atorvastatin) 20 mg.
• Pregnancy.
• breastfeeding period.

Dosage and administration

Hyperlipidemia (heterozygous familial and non-familial) and mixed dyslipidemia (type IIa and IIb, according to Fredrickson’s classification).

The recommended starting dose of atorvastatin is 10 or 20 mg once daily. For patients who require a significant reduction in LDL cholesterol (greater than 45%), therapy may be initiated at a dosage of 40 mg once daily. The dosing range for atorvastatin is 10 to 80 mg once daily. The drug can be taken as a single dose at any time and regardless of food intake. The initial and maintenance doses of atorvastatin should be individualized depending on the goal of treatment and response. After initiation of treatment and/or after dose titration of atorvastatin, lipid levels should be analyzed over a period of 2 to 4 weeks and the dose adjusted accordingly.

Heterozygous familial hypercholesterolemia in pediatric patients (aged 10-17 years). The recommended starting dose of atorvastatin is 10 mg/day; the maximum recommended dose is 20 mg/day (doses exceeding 20 mg have not been studied in this group of patients). Doses of the drug should be selected individually in accordance with the recommended goal of treatment. Dose adjustments should be made at intervals of 4 weeks.

Homozygous familial hypercholesterolemia.

The dose of atorvastatin in patients with homozygous familial hypercholesterolemia is 10 to 80 mg per day. Atocor (atorvastatin) 20 mg. should be used as an adjunct to other lipid-lowering therapies (eg, LDL apheresis), or if lipid-lowering therapies are not available.

Simultaneous lipid-lowering therapy.

Atocor (atorvastatin) 20 mg. can be used with bile acid sequestrants. The combination of HMG-CoA reductase inhibitors (statins) and fibrates should generally be used with caution.

Dosage for patients with impaired renal function.

Kidney disease does not affect either plasma concentrations or LDL-C lowering with atorvastatin; therefore, dose adjustment of the drug in patients with impaired renal function is unnecessary.

Dosing for patients taking ciclosporin, clarithromycin, itraconazole, or certain protease inhibitors.

Treatment with Atocor (atorvastatin) 20 mg. should be avoided in patients taking cyclosporine or HIV protease inhibitors (tipranavir + ritonavir) or an inhibitor of hepatitis C virus protease (telaprevir). Atorvastatin should be used with caution in HIV patients taking lopinavir + ritonavir and used at the most appropriate dose. In patients taking clarithromycin, itraconazole, or in patients with HIV who are taking saquinavir + ritonavir, darunavir + ritonavir, fosamprenavir, or fosamprenavir + ritonavir, the therapeutic dose of atorvastatin should be limited to 20 mg, and appropriate clinical evaluations are recommended to ensure use of the smallest necessary dose of atorvastatin. In patients taking the HIV protease inhibitor nelfinavir or the hepatitis C protease inhibitor boceprevir.