Аторвастатин-ЛЕКСВМ®

General characteristics. Structure:

Active agent таб. - 10 mg таб. 20 mg
Atorvastatin of calcium trihydrate - 10,85 mg 21,70 mg
In terms of аторвастатин - 10,00 mg 20,00 mg
Excipients: lactoses monohydrate, gelatin, polysorbate 80, croscarmellose sodium, microcrystallic cellulose, corn starch, magnesium stearate, calcium carbonate.
Cover: gipromelloza, titanium dioxide, propylene glycol, talc.

Opisaniye:tabletki of a kapsulovidny form, film coated, white or almost white color, smooth on both sides.

Chemical name: [R (R*R *)]-2-(4-Ftorfenit) - a beta, delta-digidroksi-5-(1 methylethyl) - 3-fenil-4-[(phenyl amine) a carbonyl] - 1H-pyrrol-1-heptanoic acid calcic salt.

Pharmacological properties:

Pharmacodynamics. Hypolipidemic means from group of inhibitors of GMG-KOA-reduktazy (statines).

The selection competitive inhibitor of GMG-KOA-reduktazy — the enzyme turning 3-hydroxy-3-methylglutaryl a coenzyme And into mevalonovy acid, being the predecessor of sterol including cholesterol.

Triglycerides (TG) and cholesterol in a liver are included lipoproteids of very low density (LPONP), at synthesis in a liver come to a blood plasma and are transported in peripheral fabrics. Lipoproteids of the low density (LPNP) are formed of LPONP during interaction with LPNP receptors.

Reduces concentration of cholesterol and lipoproteins in a blood plasma due to oppression of GMG-KOA-reduktazy, synthesis of cholesterol in a liver and increases in number of "hepatic" receptors of 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 the hypolipidemic medicines (M).

In doses of 40 mg reduces concentration of the general cholesterol by 30 — 46%, LPNP — for 41 — 61%, apolipoprotein B — for 34 — 50% and TG — for 14 — 33%; causes a povysheniyekotsentration holesterina-LPVP and apolipoprotein A.

Dozozavisimo reduces concentration of LPNP at patients with a homozygous hereditary hypercholesterolemia, resistant to therapy in other hypolipidemic HP.

Authentically 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. Absorption — high. Time of achievement of the maximum concentration (TCmax) — 1-2 h, the maximum concentration of active ingredient in a blood plasma (Cmax) at women is 20% higher, the area under a curve "concentration of active ingredient – time" (AUC) — is 10% lower; Cmax at patients with alcoholic cirrhosis by 16 times, AUC — is 11 times higher than norm. Food reduces the speed and duration of absorption of drug a little (by 25% and 9% respectively), however decrease in LPNP cholesterol is similar to that at use of an atorvastatin without food. Concentration of an atorvastatin at use is lower in the evening, than in morning (approximately for 30%). Linear dependence between extent of absorption and a dose of drug is revealed. Bioavailability — 14%, system bioavailability of the inhibiting activity concerning GMG-KOA-reduktazy — 30%. Low system bioavailability is caused by presistemny metabolism in a mucous membrane of digestive tract and at "the first passing" through a liver.

The average volume of distribution — 381 l, communication with proteins of plasma — more than 98%. It is metabolized preferential in a liver under the influence of isoenzymes of CYP3A4, CYP3A5 and CYP3A7 with formation pharmacological of active metabolites (orto-and parahydroxylated derivatives, beta oxidation products).

In vitro orto-and parahydroxylated metabolites have an inhibiting effect on GMG-KOA-reduktazu, comparable to that of an atorvastatin. The inhibiting effect of drug concerning GMG-KOA-reduktazy approximately is defined on 70% by activity of the circulating metabolites and about 20 — 30 h thanks to their existence remain. An elimination half-life (T1/2) — 14 h. It is removed with bile after hepatic and/or extrahepatic metabolism (is not exposed to the expressed enterohepatic recirculation). Less than 2% of the dose of drug accepted inside are defined in urine.

It is not removed during a hemodialysis owing to intensive linkng with proteins of plasma.

At a liver failure at patients with alcoholic cirrhosis (Chayld-Pyyug of B)C of max and AUC considerably raise (in 16 and 11 times, respectively).

Cmax and AUC drug at elderly (65 years are more senior) for 40 and 30%, respectively above those at adult patients of young age (clinical value has no). Cmax at women is 20% higher, and those AUC 10% lower at men (clinical value has no).

The renal failure does not influence concentration of drug in plasma.

Indications to use:

Primary hypercholesterolemia (heterozygous family and single hypercholesterolemia of IIa of type), the combined (mixed) lipidemia (IIb and IIA of type across Fredrikson); with the increased maintenance of TG in a blood plasma (type IV across Fredrikson); a disbetalipoproteinemiya (the III type) (as addition to a diet), a family endogenous gipertriglitseridemiya (the IV type), only when the diet and other not pharmacological methods of treatment are insufficiently effective.

Homozygous hereditary hypercholesterolemia (as addition to hypolipidemic therapy).

Route of administration and doses:

Inside, to accept at any time, but at the same time, irrespective of meal. Before therapy to the patient appoint a standard gipokholesterinemichesky diet to all the time of treatment.

The dose fluctuates from 10 to 80 mg a day and is selected taking into account initial concentration of cholesterol, the purpose of therapy and individual effect. For most of patients the initial dose makes 10 mg of 1 times a day.

At primary giperkholesterininemiya and the combined (mixed) lipidemia appoint 10 mg once a day. The effect is shown during 2 weeks, the maximum effect is observed within 4 weeks.

At a liver failure of a dose it is necessary to reduce. At a renal failure and correction of doses of drug is not required from patients of advanced age.

At a homozygous family hypercholesterolemia apply 40-80 mg of 1 times a day (decrease in maintenance of LPNP by 18-45%).

Use at pregnancy and during breastfeeding

Contraindicated at pregnancy.

Women of reproductive age should apply reliable methods of contraception. As the cholesterol and substances synthesized from cholesterol are important for fetation, the potential risk of inhibition of HMG-CoA reductase exceeds advantage of use of drug during pregnancy. At use by mothers in the I trimester of pregnancy of a lovastatin (GMG-KOA inhibitor – reductase) with dekstroamfetaminy cases of the birth of children with deformation of bones, tracheooesophageal fistula, an anus atresia are known. In case of pregnancy in the course of therapy administration of drug has to be immediately stopped, and patients are warned about potential risk for a fruit.

It is allocated in breast milk. For the period of treatment it is necessary to stop breastfeeding.

Features of use:

Atorvastatin can cause increase in indicators of serumal KFK that it is necessary to take into account at differential diagnosis of retrosternal pains. It must be kept in mind that the increase in KFK by 10 times in comparison with norm which is followed by a mialgiya and muscular weakness can be connected with a myopathy, treatment should be stopped. 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 use (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 indicators of 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, a lowering of arterial pressure, extensive operative measures, an injury, the metabolic, endocrine or expressed electrolytic disturbances).

Patients need to be warned that they should see immediately a doctor at emergence of inexplicable pains or weakness in muscles, especially if they are followed by an indisposition or fever. The risk of a myopathy increases at simultaneous use of cyclosporine, derivatives of fibroyevy acid, erythromycin, niacin or azolovy antifungal drugs.

Side effects:

Most often (1% and more): sleeplessness, headache, asthenic syndrome; nausea, diarrhea, abdominal pain, dyspepsia, meteorism, lock; mialgiya.

Less frequent (less than 1%):
From a nervous system: — indisposition, dizziness, amnesia, paresthesia, peripheral neuropathy, hypesthesia.
From the alimentary system: vomiting, anorexia, hepatitis, pancreatitis, holestatitchesky jaundice.
From a musculoskeletal system: dorsodynia, myotonia, miositis, myopathy, arthralgia, рабдомиолиз.
Allergic reactions: urticaria, itch, skin rash, anaphylaxis, violent rash, polymorphic exudative erythema (including Stephens-Johnson's syndrome), Lyell's disease.
From bodies of a hemopoiesis: thrombocytopenia.
From a metabolism: hypo - or a hyperglycemia, increase in activity of serumal KFK.
Others: impotence, peripheral hypostases, increase in body weight, stethalgia, secondary renal failure, alopecia, sonitus.

Interaction with other medicines:

At co-administration of cyclosporine, fibrat, erythromycin, a klaritromitsin, the immunodepressive, antifungal HP (relating to azoles) and niacinamide concentration of an atorvastatin in plasma (and risk of emergence of a myopathy) raises.

At simultaneous use of an atorvastatin and erythromycin (on 500 mg 4 times a day) or the klaritromitsina (on 500 mg 2 times a day) is noted increase in concentration of an atorvastatin in a blood plasma.

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

At simultaneous use of an atorvastatin (on 10 mg of 1 times a day) and azithromycin (on 500 mg of 1 times a day) concentration of an atorvastatin in plasma does not change.

Clinically significant interaction is not noted at simultaneous use with warfarin, Cimetidinum, phenazone.

Simultaneous use of an atorvastatin with the inhibitors of proteases known as CYP3A4 isoenzyme inhibitors, is followed by increase in concentration of an atorvastatin in plasma (at odnovrmenny use with Cmax erythromycin of an atorvastatin increases by 40%).

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.

At simultaneous use of an atorvastatin of 80 mg and an amlodipina of 10 mg the pharmacokinetics of an atorvastatin did not change.

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

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

Contraindications:

Hypersensitivity to drug components, active diseases of a liver, increase in activity of "hepatic" transaminases (more than by 3 times in comparison with the upper bound of norm) not clear genesis, pregnancy, the breastfeeding period, children's age up to 18 years (efficiency and safety are not established).

With care:
- alcoholism, alcohol abuse
- liver diseases in the anamnesis
- heavy disturbances of electrolytic balance endocrine and metabolic disturbances
- arterial hypotension
- heavy acute infections (sepsis)
- uncontrollable epilepsy
- extensive surgical interventions
- injuries.

Overdose:

Symptoms: development of a myopathy with the subsequent rabdomioliz and an acute renal failure. At the same time drug has to be immediately cancelled.

Treatment: there is no specific antidote. Symptomatic therapy is carried out. Take measures for maintenance of the vital functions of an organism and a measure for the prevention of further absorption of drug: gastric lavage, reception of absorbent carbon. As аторвастатин substantially contacts proteins of a blood plasma, the hemodialysis is ineffective.

Storage conditions:

In the dry place at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to apply on expiry date.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated 10 mg, 20 mg. On 10 tablets in the blister (blister strip packaging) from PVC Is scarlet/is scarlet or scarlet/. On 3 or 6 blisters place in a cardboard pack together with the application instruction.