Atorvastatin

General characteristics. Structure:

Active ingredient: 10 mg or 20 mg of an atorvastatin in the form of calcium salt.

Hypolipidemic means.

Pharmacological properties:

Pharmacodynamics. Atorvastatin - hypolipidemic means from group of statines. Is the selection competitive inhibitor of GMG-KOA-reduktazy - the enzyme turning 3-hydroxy-3-methylglutaryl coenzyme A into mevalonovy acid, being the predecessor of sterol including cholesterol. Reduces levels of cholesterol and lipoproteins in plasma due to oppression of GMG-KOA-reduktazy, synthesis of cholesterol in a liver and increases in number of "hepatic" receptors of lipoproteins of the low density (LPNP) at surfaces of cells that leads to strengthening of capture and a catabolism of LPNP.

Reduces formation of LPNP, causes the expressed and permanent increase in activity of LPNP-receptors. Reduces the LPNP level at patients with a homozygous family hypercholesterolemia which usually does not give in to therapy by hypolipidemic medicines. Reduces the level of the general cholesterol, LPNP cholesterol, apolipoprotein B and triglycerides; causes increase in level of cholesterol lipoproteins of high density and A. Dozozavisimo's apolipoprotein reduces the LPNP level at patients with the homozygous hereditary hypercholesterolemia steady against therapy with other hypolipidemic medicines.

Reduces risk of development of ischemic complications (including development of death from a myocardial infarction), risk of repeated hospitalization concerning the stenocardia which is followed by symptoms of ischemia of a myocardium. Has no cancerogenic and mutagen effect. The therapeutic effect is reached in 2 weeks after the beginning of therapy, reaches a maximum in 4 weeks and remains during the entire period of treatment.

Pharmacokinetics. It is metabolized preferential in a liver under the influence of CYP3A4, CYP3A5 and CYP3A7 cytochrome with formation of active metabolites. It is not removed during a hemodialysis owing to intensive linkng with proteins of plasma.

At a liver failure at patients with alcoholic cirrhosis concentration of drug in blood considerably increases. The renal failure does not influence concentration of drug in plasma.

Indications to use:

- primary hypercholesterolemia (heterozygous family and single hypercholesterolemia, IIa type),

- the combined (mixed) lipidemia (IIb and III types),

- a disbetalipoproteinemiya (type III), as addition to a diet,

- a family endogenous gipertriglitseridemiya (type IV), resistant to dietary methods of treatment.

- a homozygous hereditary hypercholesterolemia (as addition to hypolipidemic therapy, including autohemotrasfusion of the blood purified of LPNP).

- diseases of cardiovascular system (including at the patients without clinical displays of coronary heart disease but having the increased risk factors of its emergence – advanced age is more senior than 55 years, nicotine addiction, arterial hypertension, genetic predisposition), including against the background of a dislipidemiya - secondary prevention for the purpose of decrease in total risk of death, a myocardial infarction, a stroke, repeated hospitalization concerning stenocardia and need for revascularization.

Route of administration and doses:

Inside, to accept at any time, irrespective of meal. Prior to therapy it is necessary to pass to the diet providing decrease in lipids in blood and to observe it during the whole time of treatment.

At prevention of coronary heart disease an initial dose for adults - 10 mg of 1 times a day. It is necessary to change a dose with an interval of not less than 2-4 weeks under control of lipidic indicators in plasma. The maximum daily dose - 80 mg in 1 reception. At a concomitant use with cyclosporine the maximum daily dose of an atorvastatin makes 10 mg; with klaritromitsiny - 20 mg; with itrakonazoly - 40 mg.

At primary hypercholesterolemia and the combined (mixed) lipidemia on 10 mg of 1 times a day. The effect is shown within 2 weeks, the maximum effect is observed within 4 weeks.

At a homozygous family hypercholesterolemia appoint 80 mg of 1 times a day (decrease in maintenance of LPNP by 18-45%). Before therapy the patient needs to appoint a standard gipokholesterinemichesky diet which he has to observe during treatment. At a liver failure of a dose it is necessary to reduce. Children are from 10 to 17 years old (only boys and the menstruating girls) at a heterozygous family hypercholesterolemia an initial dose – 10 mg of 1 times for about days. It is necessary to raise a dose not earlier than in 4 weeks and more. The maximum daily dose – 20 mg (use of doses over 20 mg is not studied).

Elderly people and patients with diseases of kidneys do not need to change the dosing mode.

Patients need to be careful with abnormal liver functions in connection with delay of removal of drug from an organism. It is necessary to control carefully clinical and laboratory indicators of function of a liver and at their considerable pathological changes a dose it is necessary to reduce or cancel drug.

Features of use:

At emergence at emergence of inexplicable pains or weakness in muscles, especially if they are followed by an indisposition or fever it is necessary to see a doctor immediately. At simultaneous use of an atorvastatin with inhibitors of proteases of CYP3A4 cytochrome (cyclosporine, кларитромицин, итраконазол) an initial dose should be begun with 10 mg; at a short-term course of treatment antibiotics reception of an atorvastatin should be cancelled. It is regularly necessary to control indicators of function of a liver before an initiation of treatment, in 6 and 12 weeks after the beginning of use of drug or after increase in a dose, and also periodically (each 6 months) during the entire period of treatment (before full normalization of a condition of patients at whom levels of transaminases exceed normal).

Increase in indicators of "hepatic" transaminases is observed generally in the first 3 months of use of drug. It is recommended to cancel drug or to lower a dose at increase in activity of "hepatic" enzymes (nuclear heating plant and ALT) more than by 3 times. It is necessary to stop temporarily use of an atorvastatin at development of the clinical symptomatology assuming existence of an acute myopathy or in the presence of the factors contributing to development of an acute renal failure against the background of a rabdomioliz (heavy infections, decrease in the ABP, extensive operative measures, an injury, the metabolic, endocrine or expressed electrolytic disturbances). Women of reproductive age should apply reliable methods of contraception. In case of pregnancy in the course of therapy, administration of drug has to be immediately stopped. Due to the potential risk for a fruit.

Influence on ability to management of transport and potentially dangerous mechanisms: messages on adverse influence of an atorvastatin on concentration of attention are not available.

Side effects:

From a nervous system: often - sleeplessness, a headache, an asthenic syndrome; the indisposition, dizziness is rare - peripheral neuropathy; very seldom - amnesia, paresthesia, a hypesthesia.

From the alimentary system: often - nausea, diarrhea, abdominal pain, dyspepsia, a meteorism, a lock; seldom - vomiting, anorexia; very seldom - hepatitis, pancreatitis, cholestatic jaundice.

From a musculoskeletal system: often – a mialgiya, a dorsodynia, an arthralgia; seldom - myotonia, a miositis, it is very rare - a myopathy, рабдомиолиз.

Allergic reactions: seldom - urticaria, an itch, skin rash, violent rash, it is very rare - an anaphylaxis, a polymorphic exudative erythema (including Stephens-Johnson's syndrome), Layeyll's syndrome.

From bodies of a hemopoiesis: seldom - thrombocytopenia.

From a metabolism: seldom - hypo - or a hyperglycemia, increase in activity of serumal KFK.

Others: seldom - a sonitus, exhaustion, impotence, peripheral hypostases, increase in body weight, a stethalgia, an alopecia; very seldom – a hemorrhagic stroke (at a concomitant use in high doses and CYP3A4 inhibitors), a secondary renal failure.

Interaction with other medicines:

At co-administration of cyclosporine, fibrat, erythromycin, a klaritromitsin, immunodepressive, antifungal medicinal (belonging to azoles) and niacinamide concentration of an atorvastatin in plasma and risk of emergence of a myopathy with rabdomiolizy and a renal failure increases.

Antacids reduce concentration by 35% (influence on the content of LPNP cholesterol does not change).

The concomitant use of an atorvastatin with warfarin can strengthen in the first days effect of warfarin on blood coagulation indicators (reduction of a prothrombin time). This effect disappears in 15 days of joint reception of the specified drugs.

Simultaneous use of an atorvastatin with the inhibitors of proteases known as CYP3A4 cytochrome inhibitors, is followed by increase in concentration of an atorvastatin in plasma.

At use of digoxin in a combination with atorvastatiny in a dose of 80 mg/days concentration of digoxin increases approximately by 20%.

Increases concentration (at appointment with atorvastatiny in a dose of 80 mg/days) the oral contraceptives containing Norethisteronum for 30% and ethinylestradiol for 20%.

The hypolipidemic effect of a combination with kolestipoly surpasses that for each drug separately, despite decrease in concentration of an atorvastatin by 25% at its simultaneous use with kolestipoly.

Simultaneous use with the medicines reducing concentration of endogenous steroid hormones (including Cimetidinum, ketokonazoly, Spironolactonum), increases risk of decrease in endogenous steroid hormones (it is necessary to be careful).

The use of grapefruit juice during treatment can lead to increase in concentration of an atorvastatin in a blood plasma. During treatment, it is necessary to avoid the use of this juice.

Contraindications:

Hypersensitivity, active diseases of a liver, increase in activity of "hepatic" transaminases (more than by 3 times) not clear genesis, the women of reproductive age who are not using adequate methods of contraception, pregnancy, the lactation period, children's age up to 18 years (efficiency and safety are not established).

With care: alcoholism, liver diseases in the anamnesis, heavy disturbances of electrolytic balance, endocrine and metabolic disturbances, arterial hypotension, a hemorrhagic stroke, heavy acute infections (sepsis), uncontrollable epilepsy, extensive surgical interventions, an injury.

Overdose:

Symptoms: specific characters of overdose are not established. Pains in a liver, an acute renal failure can be probable symptoms; at prolonged use a myopathy and рабдомиолиз.

Treatment: there is no specific antidote, symptomatic therapy and actions for the prevention of further absorption (a gastric lavage and reception of absorbent carbon). Atorvastatin substantially contacts proteins of a blood plasma owing to what, the hemodialysis is inefficient. At development of a myopathy, with the subsequent rabdomioliz and an acute renal failure (seldom) - immediate drug withdrawal and administration of diuretic and solution of Natrii hydrocarbonas. Rabdomioliz can lead to development of a giperkalemiya which elimination requires intravenous administration of calcium chloride or a gluconate of calcium, infusion of glucose with insulin, use of ion exchangers of potassium ions or, in hard cases of carrying out a hemodialysis.

Issue conditions:

According to the recipe

Packaging:

Tablets, coated, 10 mg or 20 mg in packaging No. 10 (1x10 in a blister strip packaging) or No. 30 (3x10 in blister strip packagings).