Etset

General characteristics. Structure:

Active ingredient: atorvastatin; 1 tablet contains an atorvastatin of calcium is equivalent to an atorvastatin of 10 mg or 20 mg.

Auxiliary veshchestva:laktoza monohydrate, cellulose microcrystallic, calcium carbonate, K30 povidone, sodium of a kroskarmelloz, silicon dioxide colloid anhydrous, magnesium stearate, Opadry 03F84827 covering pink.

Pharmacological properties:

Pharmacodynamics. Atorvastatin – hypolipidemic means, the selection competitive inhibitor of GMG-KOA-Reduktazy. More effective drug, than other groups of statines. At patients with a hypercholesterolemia and a gipertriglitseridemiya effectively reduces levels of the general cholesterol (by 30–46%), LPNP cholesterol (for 41–61%), triglycerides (for 14–33%), apolipoprotein B (for 34–50%) in blood serum, renders assistance to increase in levels of LPVP cholesterol (lipoproteids of high density) and A-1 apolipoprotein. Thereof the risk of the cardiovascular diseases and fatal cases connected with these diseases goes down. Perhaps also use of drug for patients with a homozygous family hypercholesterolemia at which other hypolipidemic drugs are ineffective.
Primary therapeutic effect is usually noted within 2 weeks from an initiation of treatment, maximum – in 4 weeks which remains at a constant maintenance therapy. Decrease in level of LPNP cholesterol substantially depends on a drug dose, than on its system concentration.

Pharmacokinetics. After intake аторвастатин it is quickly absorbed in a food path; extent of absorption increases in proportion to the accepted dose. The maximum concentration in plasma (Cmax) is reached in 1–2 hours. Absolute bioavailability low (about 12%), system availability of the inhibiting activity GMG-KOA-Reduktazy – about 30% is relative. Use of drug together with food reduces the speed and extent of absorption of an atorvastatin approximately by 25% and 9%, respectively, however, it significantly does not influence expressiveness of its hypolipidemic action. Extent of decrease in level of LPNP cholesterol does not depend on use time within a day though reception of an atorvastatin provides its higher concentration in a blood plasma in the morning. Not less than 98% of an atorvastatin contact proteins of a blood plasma. According to experimental data, аторвастатин it is allocated in breast milk.
Atorvastatin is metabolized by P4503A4 cytochrome to active orto-and parahydroxylated metabolites with which about 70% of its pharmacological activity are connected. Atorvastatin and his metabolites are removed, generally with bile; less than 2% – are removed with urine. The elimination half-life of an atorvastatin – about 14 hours, however an elimination half-life of ingibirushchy effect concerning GMG-KOA-Reduktazy makes 20–30 hours thanks to action of active metabolites.

Hypolipidemic effects of an atorvastatin significantly do not differ at patients of different age groups in spite of the fact that at reception in equal doses its Cmax and the area under a curve "concentration time" (AUC) at healthy volunteers of the senior age group (over 65 years) is higher, than at young patients. At women the maximum concentration of an atorvastatin in a blood plasma is about 20% higher, and AUC value – is 10% lower, than at men, however a difference in operation on extent of decrease in level of LPNP cholesterol at treatment atorvastatiny patients of both floors is not revealed.
At diseases of kidneys extent of decrease in level of LPNP cholesterol in plasma under the influence of an atorvastatin does not change that does not demand dose adjustment for such patients. The hemodialysis, most likely, has no the significant stimulating effect on clearance of an atorvastatin as drug substantially contacts proteins of plasma. Concentration of an atorvastatin in a blood plasma can sharply (at 4-16 times) to raise at patients with cirrhosis and some other serious illness of a liver.

Indications to use:

As addition to a diet for treatment of patients with the increased level of the general cholesterol, the cholesterol lipoproteins of low density (CLLD), apolipoprotein B, triglycerides, for the purpose of increase the cholesterol lipoproteins of high density (CLHD) at patients with primary hypercholesterolemia (a heterozygous family and not hereditary hypercholesterolemia) combined (mixed) lipidemia (Fredriksonovsky type ІІ and and ІІ b), the increased level of triglycerides in blood serum (Fredriksonovsky type IV) and patients with a disbetalipoproteinemiya (Fredriksonovsky type ІІІ) in cases when the diet does not provide appropriate effect.
For decrease in level of the general cholesterol and HLNP at patients with a homozygous family hypercholesterolemia when the diet and other non-drug means do not provide appropriate effect.
To patients without clinical displays of cardiovascular diseases, with existence or lack of a dislipidemiya, but at which several risk factors of cardiovascular diseases, such as tobacco smoking, arterial hypertension, a diabetes mellitus, the HLVP low level or existence in the family anamnesis of information on a disease of cardiovascular diseases in young age on purpose:

- decrease in risk of fatal displays of coronary heart disease and not fatal myocardial infarction;
- decrease in risk of developing of a stroke;
- decrease in risk of developing of stenocardia and need of performing procedures of revascularization of a myocardium.

At patients with clinical symptoms of coronary diseases аторвастатин it is shown for:

- decrease in risk of development of not fatal myocardial infarction;
- decrease in risk of development of a fatal and not fatal stroke;
- decrease in risk when holding procedures of revascularization;
- decrease in risk of hospitalization concerning congestive heart failure;
- decrease in risk of developing of stenocardia.

Children (10–17 years).
Етсет® appoint as addition to a diet for decrease in level of the general cholesterol, HLNP and apolipoprotein B at boys and girls during the postmenarkhialny period, age from 10 to 17 years with a heterozygous family hypercholesterolemia, even on condition of observance of an adequate diet if:
a) the HLNP level remains? 190 mg/dl or
b) the HLNP level remains? 160 mg/dl and:
• in the family anamnesis takes place of developing of cardiovascular diseases at young age;
• at sick children two or more other risk factors of developing of cardiovascular diseases take place.

Route of administration and doses:

Before therapy by the drug Etset® it is necessary to carry out test to control hypercholesterolemia level by means of the corresponding diet, to appoint the physical exercises and measures directed to a body degrowth at patients with obesity and to carry out treatment of other associated diseases. During treatment by the drug Etset® patients need to adhere standard cholesterol - the lowering diet. Drug appoint in a dose 10–80 mg of 1 times in days daily, at any time, irrespective of meal. The initial and supporting doses have to approach individually, according to a reference value of the HLNP level, the purpose of treatment and for sensitivity of the patient drug. In 2–4 weeks after an initiation of treatment and/or after titration of a dose of the drug Etset® it is necessary to check the level of lipoproteids and, depending on results of the analysis, respectively to modify a drug dosing.

Primary hypercholesterolemia and the combined (mixed) lipidemia. For most of patients the dose of 10 mg a day is effective. The therapeutic effect is reached within 2 weeks, the maximum therapeutic effect – within 4 weeks. The effect is supported during long treatment.

Homozygous family hypercholesterolemia. At most of patients with a homozygous family hypercholesterolemia the result is achieved owing to use of 80 mg of an atorvastatin of 1 times in days that provides decrease in the HLNP level more than for 15% (18–45%).
Heterozygous family hypercholesterolemia in pediatric practice (10-17-year-old patients). It is recommended to appoint Etset® in an initial dose on 10 mg of 1 times in days. The maximum recommended dose makes 20 mg of 1 times in days (doses which exceed 20 mg, were not studied at patients of this age group). The dose is defined individually, depending on the treatment purpose. Every 4 week or it is necessary to adjust a drug dose more.

Use for treatment of patients with a liver failure.
See the section "Contraindications" and "Features of Use".
Use for treatment of patients with a renal failure. Diseases of kidneys do not influence concentration of an atorvastatin or decrease in the HLNP level in a blood plasma. Thus, there is no need for dose adjustment.

Use for treatment of elderly patients. In safety, efficiency or achievement of the goal in treatment of a hypercholesterolemia elderly patients and patients of other age groups have no difference.

Use in a combination with other medicines.
If there is a need of simultaneous use of an atorvastatin and cyclosporine, the dose of an atorvastatin should not exceed 10 mg (see the section "Features of Use" – Action on skeletal muscles, the section "Interaction with Other Medicines" – transferring Inhibitors).

Features of use:

Influence on a liver. As well as at use of other gipolipoproteinemichesky means of the same class, at treatment atorvastatiny there can be a moderate increase in activity of transaminases of blood serum (three times more, than the top level of norm – VUN). Function of a liver was controlled on pre-and post-marketing stages of a research of use of an atorvastatin in doses of 10, 20, 40 and 80 mg. Persistent increase in activity of transaminases (it is three times more, than VUN in 2 or more cases) was observed at 0,7% of patients who received аторвастатин throughout these researches. Limits of these deviations made 0,2, 0,2, 0,6 and 2,3% at use of 10, 20, 40 and 80 mg of drug, respectively. Increase in activity of transaminases was not followed by jaundice or other clinical manifestations. If the dose of an atorvastatin was reduced, did a break or stopped treatment, the level of transaminases was normalized. Most of patients continued treatment by smaller doses of an atorvastatin without negative effects.
Function of a liver has to be defined before an initiation of treatment and be controlled periodically throughout a course of treatment. Patients who have manifestations of an abnormal liver function need to define indicators of its function. Patients at whom increase in activity of transaminases is observed have to be under observation up to normalization of indicators. In case of more than thrice growth of activity Alat or Asat above norm a dose of an atorvastatin it is necessary to reduce or stop treatment. Atorvastatin can cause increase in activity of transaminases.
Етсет® patients who take alcohol and/or who have a liver disease in the anamnesis need to appoint with care. Liver diseases in an active phase or increase in activity of transaminases for the unclear reason are a contraindication for purpose of the drug Etset®.

Influence on skeletal muscles. During treatment by drug at patients the myopathy can be observed. It is necessary to understand muscle pain or weakness of muscles in combination with growth of level of a kreatinfosfokinaza (KFK) by 10 times over VUN as a myopathy. The probability of emergence of this state needs to be assumed at patients with a diffusion mialgiya, morbidity or weakness of muscles and/or essential increase in level of a kreatinfosfokinaza. Patients need to be warned about possible developing of pain in muscles and weakness of muscles, sometimes with an infirmity or temperature increase. In cases of increase in the KFK level or the specified or estimated diagnosis of a myopathy treatment by drug needs to be stopped. The risk of emergence of a myopathy during treatment by drugs of this group increases at simultaneous use of cyclosporine, derivatives of fibrinous acid, erythromycin, Niacinum or azolny antifungal means. The majority of these means oppress metabolism of P450 3A4 cytochrome and/or distribution of drug in an organism. Етсет® it biotransformirutsya, first of all, by means of CYP 3A4 liver enzyme. Doctors who appoint Etset® in a combination with derivatives of fibrinous acid, erythromycin, immunosuppressors or azolny antifungal means or gipolipoproteinemichesky doses of Niacinum have to weigh possible positive takes and harmful effects and watch patients for the purpose of identification of such manifestations as muscle pain and weakness of muscles, especially in the first months of treatment and after increase in a dose of one of these drugs. Periodic definition of KFK is for this purpose recommended, however it is necessary to remember that this test is not enough for timely diagnosing of a heavy myopathy. Етсет® can cause growth of the KFK level.

At treatment the drug Etset®, as well as at use of similar drugs of this group, occasionally observed cases of a rabdomioliz in a combination to a secondary renal failure which is caused by a myoglobinuria. Therapy atorvastatiny needs to be interrupted or stopped in case of serious condition of the patient at suspicion that these changes are caused by a myopathy, or with risk factors of development of a secondary renal failure at a rabdomioliza (for example, a heavy acute infection, arterial hypotension, serious surgical interventions, an injury, heavy endocrine, metabolic or electrolytic disturbances and uncontrollable spasms). The short termination of administration of drug of Etset® does not pose direct threat. If treatment was stopped on more long period, the vascular disease because of accumulation of fats in walls of vessels can progress (atherosclerosis) and there can be a risk of a recurrence of a cardiovascular disease.
Drug contains lactose that patients need to consider with a hereditary lactose intolerance.

Ability to influence speed of response at control of motor transport or work with other mechanisms. It is unknown.

Use during pregnancy or feeding by a breast.
Drug is contraindicated during pregnancy. Women of reproductive age have to apply effective methods of contraception. Етсет® appoint to women of reproductive age only in that case when probability to become pregnant very low and the patient it is informed rather potential risk for a fruit.
Drug is contraindicated during feeding by a breast. It is not known whether this drug in breast milk is excreted. As there is a potential risk of development of side effects in children who are on breastfeeding, women who accept Etset® have to stop feeding by a breast.

Children. Controlled clinical trials of an atorvastatin at patients were not conducted by age up to 10 years with a heterozygous family hypercholesterolemia.

Side effects:

Atorvastatin is usually well had. Side effects in most cases easy severity and temporary.
The most frequent side effects associated with reception of an atorvastatin:

- disturbance of mentality: sleeplessness;
- dysfunction of a nervous system: headache;
dysfunction of a food path: nausea, diarrhea, abdominal cavity pain, dyspepsia, lock, meteorism;
- dysfunction of skeletal and muscular system and connecting fabric: mialgiya;
general disturbances: adynamy.
Are also possible:
- disturbance of metabolism and food: hypoglycemia, hyperglycemia, anorexia;
- dysfunction of a nervous system: peripheral neuropathy, paresthesia;
- dysfunction of a food path: pancreatitis, vomiting;
- abnormal liver function and gall bladder: hepatitis, cholestatic jaundice;
- disturbance of skeletal and muscular system and connecting fabric: myopathy, miositis, spasms;
- skin and connecting fabric: alopecia, itch, rash;
- dysfunction of reproductive system: impotence.
- The most widespread side effects:
- dysfunction of circulatory and lymphatic system: thrombocytopenia;
- dysfunction of immune system: allergic reactions (including acute anaphylaxis);
- damage, poisoning and complication of procedures: rupture of a sinew;
- disturbance of metabolism and food: increase in body weight;
- dysfunction of a nervous system: hypesthesia, amnesia, dizziness, dysgeusia;
- skin and hypodermic fabric: Stephen-Johnson's syndrome, toxic epidermal necrolysis, exudative multiformny erythema, violent rash, small tortoiseshell;
- dysfunction of skeletal and muscular system and connecting fabric: рабдомиолиз, arthralgia, dorsodynia;
- general disturbances: stethalgia, peripheral hypostasis, indisposition, fatigue.

Interaction with other medicines:

The risk of emergence of a myopathy during treatment by inhibitors of GMG-KOA-Reduktazy increases at simultaneous use of cyclosporine, fibrat, niacin or inhibitors of P450 3A4 cytochrome (for example, erythromycin, azolny antifungal drugs).
- Inhibitors of P450 3A4 cytochrome. Atorvastatin is metabolized by means of P450 3A4 cytochrome. Simultaneous use of an atorvastatin with inhibitors of P450 3A4 cytochrome can lead to increase in concentration of an atorvastatin in a blood plasma. Force of interaction and potentiation of effect depends on variability of action on P450 3A4 cytochrome.
- Transferring inhibitors
Atorvastatin and metabolites of an atorvastatin are OATP1B1 conveyor substrates. OATP1B1 inhibitors (for example, cyclosporine) can increase bioavailability of an atorvastatin. Simultaneous use of 10 mg of an atorvastatin and cyclosporine (5,2 mg/kg in days) leads to increase in exposure to an atorvastatin by 7,7 times.
- Erythromycin / кларитромицин
At simultaneous use of an atorvastatin and erythromycin (500 mg 4 times in days) or the klaritromitsina (500 mg two times in days) which are inhibitors of P450 3A4 cytochrome, raises concentration of an atorvastatin in a blood plasma.
- Protease inhibitors
Owing to simultaneous use of an atorvastatin and inhibitors of protease, well-known inhibitors of P450 3A4 cytochrome, concentration of an atorvastatin in a blood plasma increases.
- Diltiazema hydrochloride
The concomitant use of an atorvastatin (40 mg) and diltiazem (240 mg) is followed by increase in concentration of an atorvastatin in a blood plasma.
- Cimetidinum
As a result of the conducted researches of signs of interaction of an atorvastatin and Cimetidinum it is not revealed.
- Itrakonazol
Simultaneous use of an atorvastatin (20 and 40 mg) and itrakonazola (200 mg) was followed by increase in an indicator of AUC of an atorvastatin.
- Grapefruit juice
Contains one or more components which inhibit CYP 3A4 and can increase concentration of an atorvastatin in a blood plasma, especially at the use of juice it is more than 1,2 l/days.

Inductors of P450 3A4 cytochrome

Co-administration of an atorvastatin and inductors of P450 3A4 cytochrome (for example, efavirenets, Rifampinum) can lead to reduction of concentration of an atorvastatin in a blood plasma. In view of the double mechanism of action of Rifampinum (induction of P450 3A4 cytochrome and an ingibition of OATP1B1 enzyme carrier in a liver), it is recommended to appoint аторвастатин along with Rifampinum as reception of an atorvastatin after reception of Rifampinum leads to considerable decrease in level of an atorvastatin in a blood plasma.
- Antacids
Simultaneous peroral purpose of an atorvastatin and peroral suspension of antiacid drug which contains magnesium and aluminum hydroxide is followed by decrease in concentration of an atorvastatin in a blood plasma approximately for 35%. At the same time hypolipidemic action of an atorvastatin did not change.
- Antipyrine
Because аторвастатин does not influence antipyrine pharmacokinetics, a possibility of interaction with other medicines which are acquired by the same tsitokhromny isoenzymes, it is considered improbable.
- Kolestipol
Concentration of an atorvastatin in a blood plasma was lower (approximately for 25%) at co-administration of an atorvastatin and kolestipol. At the same time hypolipidemic action of a combination of an atorvastatin and kolestipol exceeded effect which gives reception of each of these drugs separately.
- Digoxin
The reusable concomitant use of digoxin and 10 mg of an atorvastatin was not followed by increase in equilibrium concentration of digoxin in a blood plasma. At the same time, use of digoxin and 80 mg of an atorvastatin led to increase in concentration of digoxin approximately for 20%. Patients who accept digoxin have to be under the corresponding supervision.
- Azithromycin
Co-administration of an atorvastatin (10 mg of 1 times in days) and azithromycin (500 mg of 1 times in days) was not followed by changes of concentration of an atorvastatin in a blood plasma.
Oral contraceptives
Simultaneous use of an atorvastatin and oral contraceptives which part norethindrone and ethinylestradiol is was followed by increase in indicators of AUC for these components respectively for 30% and 20%. This fact of increase needs to be considered at the choice of an oral contraceptive for women who accept аторвастатин.
- Warfarin
Clinically significant interaction of an atorvastatin with warfarin is not revealed.
- Amlodipin
Healthy volunteers have a simultaneous use of 80 mg of an atorvastatin and 10 mg of an amlodipin was followed by increase in concentration of an atorvastatin in a blood plasma approximately for 18% and had no clinical value.
- Other medicines
Clinical trials showed that simultaneous use of an atorvastatin and hypotensive drugs and its use during replacement therapy by estrogen was not followed by clinically significant side effects. Interaction researches with other drugs were not conducted.

Contraindications:

Hypersensitivity to any component of drug. A liver disease in an acute phase or at permanent increase (unknown genesis) in levels of transaminases in blood serum in three and more times, and also to pregnant women, women who nurse or to women of childbearing age who do not apply effective methods of contraception. Етсет® it can be appointed to women of childbearing age only when an opportunity is improbable to become pregnant, and they were informed on potential undesirable effects for a fruit.

Overdose:

Specific treatment at overdose of an atorvastatin does not exist. In drug overdose cases if necessary carry out a symptomatic and maintenance therapy. As аторвастатин extensively contacts proteins of a blood plasma, the hemodialysis cannot significantly increase clearance of an atorvastatin.

Storage conditions:

To store in the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 14 tablets in the blister; on 2 blisters in cardboard packaging.