Zovastikor, tablets

General characteristics. Structure:

Active ingredient: 10 mg or 20 mg of a simvastatin in 1 tablet.

Excipients: sugar milk (lactose), starch corn, microcrystallic cellulose, methyl cellulose, butylhydroxyanisole, ascorbic acid, citric acid, magnesium stearate, Opadray of II (including: polyvinyl alcohol, talc, a macrogoal (polyethyleneglycol), lecithin (soy) painting a pigment of green color (an aluminum varnish on the basis of yellow quinolinic (Е 104), an aluminum varnish on the basis of yellow a sunset (Е 110), an aluminum varnish on the basis of indigo carmine (Е 132)).

Pharmacological properties:

Pharmacodynamics. The hypolipidemic means from group of statines received in the synthetic way from Aspergillus tereus fermentation product. Is pro-medicine as has in the structure the closed lactonic ring which after receipt in an organism is metabolized with formation of hydroxyacid derivative. The active metabolite inhibits GMG-KOA-reduktazu, the enzyme catalyzing initial reaction of formation of a mevalonat from GMG-KOA. As transformation GMG-KOA in мевалонат represents an early stage of synthesis of cholesterol, use of a simvastatin does not cause accumulation in an organism of potentially toxic sterol. GMG-KOA it is easily metabolized to atsetil-KOA which participates in many processes of synthesis in an organism.

Causes decrease in contents in a blood plasma of triglycerides, lipoproteins of the low density (LPNP), lipoproteins of very low density and the general cholesterol (in cases of heterozygous family and single forms of a hypercholesterolemia, at the mixed lipidemia when the increased content of cholesterol is risk factor). Increases the maintenance of lipoproteins of high density and reduces a ratio lipoproteins of low density / lipoproteins of high density and the general cholesterol / lipoproteins of high density. The therapeutic effect develops in 2 weeks from the beginning of reception, the maximum therapeutic effect is reached in 4-6 weeks of treatment. Action remains at treatment continuation, at the therapy termination the content of cholesterol gradually is returned to initial level.

Pharmacokinetics. Absorption: absorption of a simvastatin high. Is exposed to effect of "the first passing" through a liver. After intake of Cmax in a blood plasma it is reached approximately in 1, 3 – 2,4 h and decreases by 90% in 12 h.

Distribution: linkng with proteins of a blood plasma makes about 95%.

Metabolism. It is metabolized in a liver, hydrolyzed with formation of active derivative – beta hydroxyacids, also other active, and also inactive metabolites are found.

Removal. T1/2 of active metabolites makes 1,9 h. It is removed preferential with bile and fecal masses (60%) in the form of metabolites. About 10 - 15% are removed by kidneys in an inactive form.

Indications to use:

Primary hypercholesterolemia (the IIA and IIb type on Fredrikson's classification) and the combined hypercholesterolemia and a gipertriglitseridemiya at inefficiency of a dietotherapy with the low content of cholesterol and other non-drug actions (an exercise stress and decrease in body weight) at patients with the increased risk of developing of coronary atherosclerosis.

The Coronary Heart Disease (CHD) (for the purpose of decrease in risk of development of a myocardial infarction and a lethal outcome, and also for reduction of risk of cardiovascular disturbances (a stroke or tranzitorny ischemic attacks), delay of progressing of atherosclerosis of coronary arteries and reduction of risk of the procedure of revascularization).

Route of administration and doses:

Prior to treatment by Zovastikor the patient should appoint a standard hypocholesteric diet which needs to be observed during all course of treatment.

Zovastikor it is necessary to accept in 1 times a day in the evening, washing down with a glass of water. Zovastikor's reception is carried out regardless of meal.

At treatment of a hypercholesterolemia the recommended initial dose of Zovastikor makes 10 mg of 1 times a day in the evening. The recommended daily dose varies from 10 to 80 mg. Changes (selection) of a dose should be carried out bucketed in 4 weeks. At most of patients the optimum effect is reached at reception of medicine in doses to 20 mg/days. The maximum daily dose – 80 mg.

At a homozygous hereditary hypercholesterolemia the recommended daily dose of Zovastikor makes 40 mg of 1 times a day in the evening or 80 mg in 3 receptions (on 20 mg in the morning and in the afternoon, and 40 mg in the evening).

At treatment of an ischemic heart disease or high risk of development of an ischemic heart disease effective doses of Zovastikor make 20-40 mg/days. The recommended initial dose - 20 mg/days. Changes (selection) of a dose should be carried out bucketed in 4 weeks, if necessary it is possible to increase a dose to 40 mg/days. If the content of LPNP cholesterol less than 75 mg/dl (1,94 mmol/l), content of the general cholesterol - less than 140 mg/dl (3,6 mmol/l), Zovastikor's dose it is necessary to reduce.

And at a renal failure easy and moderate severity of correction of the mode of dosing is not required from patients of advanced age.

At patients with a chronic renal failure (KK less than 30 ml/min.) or receiving cyclosporine, даназол, gemfibrozit or other fibrata (except a fenofibrat), niacin in lipidosnizhayushchy doses (≥ 1 g/days), along with Zovastikor, the maximum recommended Zovastikor's dose should not exceed 10 mg/days. If necessary increase in a dose at this category of patients should be carried out under careful medical control.

For the patients accepting Amiodaronum or verapamil along with Zovastikor, the daily dose of Zovastikor should not exceed 20 mg.

Features of use:

Zovastikor, as well as other GMG inhibitors - To - And - reductases, it is not necessary to apply at the increased risk of development of a rabdomioliz and a renal failure (against the background of a heavy acute infection, arterial hypotension, the planned big surgery, injuries, heavy metabolic disturbances).

At the beginning of therapy by Zovastikor perhaps passing increase in level of liver enzymes.

Before therapy and further it is regularly necessary to conduct a research of function of a liver (to control activity of liver enzymes each 6 weeks within the first 3 months, then each 8 weeks within the remained first year, and then 1 time in half a year), also at increase in a dose of Zovastikor it is necessary to carry out the test for definition of function of a liver. At increase in a dose to 80 mg it is necessary to carry out the test each 3 months. At permanent increase in activity of transaminases (by 3 times in comparison with initial level) Zovastikor's reception should be stopped.

At patients with a hypothyroidism or in the presence of some diseases of kidneys (a nephrotic syndrome) at increase in level of cholesterol it is necessary to carry out therapy of a basic disease at first.

Zovastikor with care appoint to patients with an alcoholism and/or having in the anamnesis of a disease of a liver.

Prior to the beginning of and during treatment the patient has to be on a hypocholesteric diet.

At patients with a mialgiya, a myasthenia and/or the expressed increase in activity of KFK treatment with drug is stopped. Zovastikor is not shown when there is a gipertriglitseridemiya I, IV and V types.

Treatment by Zovastikor can cause the myopathy leading to a rabdomioliz and a renal failure.

The risk of development of a myopathy increases also at patients with a renal failure of heavy degree.

All patients beginning therapy by Zovastikor and also patients who need to increase a drug dose have to be warned about possibility of a myopathy and need of the immediate address to the doctor in case of developing of inexplicable pains, morbidity in muscles, slackness or muscular weakness, especially if it is followed by an indisposition or fever. Therapy by medicine has to be immediately stopped if the myopathy is diagnosed or is supposed.

For the purpose of timely diagnosis of a myopathy during treatment it is recommended to define activity of a kreatinfosfokinaza regularly.

At treatment by Zovastikor increase in maintenance of a serumal kreatinfosfokinaza is possible that should be considered at differential diagnosis of pains behind a breast. As criterion of cancellation of Zovastikor serves increase in maintenance of a kreatinfosfokinaza in blood serum more than by 10 times of rather upper bound of norm.

Zovastikor is effective both in the form of monotherapy, and in combination with sekvestrant of bile acids.

In case of the admission of the current dose Zovastikor it is necessary to accept as soon as possible. If came time of reception of the following dose, a dose not to double.

Treatment of patients with a renal failure of heavy degree is carried out under control of function of kidneys.

It is necessary to avoid a concomitant use of Zovastikor and grapefruit juice.

Influence on ability to driving of motor transport and to control of mechanisms. About adverse influence of Zovastikor on ability to management of motor transport and work with mechanisms it was not reported.

Pregnancy and lactation. Zovastikor is contraindicated at pregnancy. There are messages on development of anomalies in newborns which mothers accepted симвастатин at pregnancy.

The women of childbearing age accepting симвастатин have to avoid conception, using well-tried remedies of contraception.

If in the course of treatment pregnancy nevertheless occurred, then Zovastikor it is necessary to cancel, and the patient needs to be warned about possible danger to a fruit.

Cancellation of hypolipidemic means at pregnancy has no significant effect on results of prolonged treatment of primary hypercholesterolemia.

It is unknown whether it is allocated симвастатин with breast milk. In need of Zovastikor's appointment in the period of a lactation it is necessary to consider that many medicines are allocated with breast milk, and there is a threat of development of heavy reactions therefore feeding by a breast during administration of drug is not recommended.

Side effects:

From the alimentary system: abdominal pains, a lock, a meteorism, nausea, diarrhea, pancreatitis, vomiting, hepatitis, increase in activity of liver enzymes are possible.

From the central nervous system and peripheral nervous system: headache, sleep disorder; seldom – dizzinesses, an asthenic syndrome, muscular spasms, paresthesias, a sight vagueness, disturbance of flavoring feelings; in some cases – a depression, a peripheral neuropathy.

From a musculoskeletal system: myopathy, mialgiya, myotonia, weakness; seldom - рабдомиолиз.

From laboratory indicators: thrombocytopenia, increase in a blood sedimentation rate, eosinophilia, increase in activity of a kreatinfosfokinaza.

Allergic reactions: Quincke's disease, rheumatic polimialgiya, vasculitis, arthritis, small tortoiseshell, volchanochnopodobny syndrome.

Dermatological reactions: photosensitization, dermahemia; seldom - skin rash, an itch, an alopecia, a dermatomyositis.

Others: fever, inflows, short wind, anemia, heartbeat, an acute renal failure (owing to a rabdomioliz), decrease in a potentiality, a phacoscotasmus.

Interaction with other medicines:

The risk of development of a myopathy increases at simultaneous use of Zovastikor with one or several of the following medicines: cytostatics, fibrata (gemfibrozit, фенофибрат), immunodepressants (including cyclosporine), нефазодон, macroleads (including erythromycin, кларитромицин), antifungal means from group of azoles (including кетоконазол, итраконазол), HIV protease inhibitors (including ритонавир), high doses of niacin.

At simultaneous use of a simvastatin in high doses with cyclosporine or danazoly the risk of development of a myopathy / рабдомиолиза increases.

The risk of development of a myopathy increases at joint purpose of other hypolipidemic means which are not powerful inhibitors of an isoenzyme CYP3A4, but capable to cause a myopathy in the conditions of monotherapy. Such as gemfibrozit also other fibrata (except a fenofibrat), and also niacin in a dose> =1 g/days.

The risk of development of a myopathy increases at joint reception of Amiodaronum or verapamil with simvastatiny in high doses. At purpose of high doses of Zovastikor along with Amiodaronum, the risk of development of a rabdomioliz increases. This undesirable interaction is connected with ability of Amiodaronum to inhibit activity of an isoenzyme of the P450 CYP3A4 cytochrome which is taking part in metabolism of a simvastatin.

All patients accepting Amiodaronum and beginning therapy by Zovastikor at the planned increase in a dose of Zovastikor, have to be warned about possibility of a rabdomioliz. The accessory contributing factors of development of a rabdomioliz at Zovastikor's reception are age 65 years, an uncontrollable hypothyroidism, a renal failure are more senior. The patient also has to be informed on need of the immediate address to the doctor at emergence of any unexpected muscular pain, muscular weakness. If for decrease in level of cholesterol of a blood plasma the patient accepting Amiodaronum needs a dose of a simvastatin more than 20 mg a day it is necessary to appoint other drug from group of statines.

The risk of development of a myopathy slightly increases at the patients receiving diltiazem along with simvastatiny in a dose of 80 mg.

Simvastatin exponentiates effect of peroral anticoagulants (including a fenprokumona, warfarin) and increases risk of development of bleedings. In this regard control of indicators of coagulability of blood prior to treatment is required, and also it is rather frequent during an initial stage of therapy. As soon as the stable level of an indicator of a prothrombin time or the International Normalized Relation (MHO) is reached, further control should be carried out bucketed, recommended for the patients receiving therapy by anticoagulants. At change of a dose or the termination of reception of a simvastatin it is also necessary to carry out control of a prothrombin time or MHO according to the above scheme.

Therapy simvastatiny does not cause changes of a prothrombin time and risk of bleedings in the patients who are not accepting anticoagulants.

Simvastatin increases digoxin level in a blood plasma.

Colestyraminum and колестипол reduce bioavailability (use of a simvastatin is possible in 4 h after reception of the specified medicines, at the same time the additive effect is noted).

Juice of grapefruit contains one or more components which inhibit an isoenzyme of CYP3A4 and can increase concentration in a blood plasma of the drugs which are metabolized with the participation of CYP3A4. Increase in activity of inhibitors of GMG-KOA-reduktazy after reception of 250 ml of juice a day is minimum and has no clinical value. However consumption of large volume of juice (more than 1 l a day) at reception of a simvastatin considerably increases the level of the inhibiting activity concerning GMG-KOA-reduktazy in a blood plasma. In this regard it is necessary to avoid the grapefruit juice use in large numbers.

Contraindications:

– liver diseases (acute and aggravation of chronic), permanent increase in activity of liver enzymes of not clear etiology;

– porphyria;

– myopathy;

– children's and teenage age up to 18 years (efficiency and safety are not established);

– pregnancy;

– lactation (breastfeeding);

– hypersensitivity to a simvastatin and other components of medicine;

– hypersensitivity to other drugs of a statinovy row (GMG-KOA-reduktazy inhibitors) in the anamnesis.

With care appoint at a hypothyroidism, a hyperplasia of a prostate, supraventricular tachycardia, depressed cases; to patients with an alcoholism; after organ transplantation when performing therapy by immunodepressants (in connection with the increased risk of emergence of a rabdomioliz and a renal failure); at a chronic renal failure, insufficiency of functions of adrenal glands, and also at states which can lead to development of the expressed renal failure, such as arterial hypotension, acute infectious diseases of a heavy current, the expressed metabolic and endocrine disturbances, disturbances of water and electrolytic balance, surgical interventions (including dental) or injuries (a craniocereberal injury); to patients with the lowered or raised tone of skeletal muscles of not clear etiology; at epilepsy.

Overdose:

In one of the known several cases of overdose (the maximum accepted dose of 450 mg) of specific symptoms it is not revealed.

Treatment: it is necessary to cause vomiting, to appoint absorbent carbon; if necessary carry out symptomatic therapy. It is necessary to control functions of a liver and kidneys, the level of a kreatinfosfokinaza (KFK) in blood serum.

At development of a myopathy with rabdomiolizy and an acute renal failure (rare, but heavy side effect) it is necessary to stop immediately Zovastikor's reception, to appoint diuretic and sodium bicarbonate (intravenous infusion). If necessary the hemodialysis is shown.

Rabdomioliz can cause a hyperpotassemia which can be eliminated in/in introduction of Calcii chloridum or calcium of a gluconate, infusion of glucose with insulin, use of potassium ion-exchange drugs or, in hard cases, by means of a hemodialysis.

Storage conditions:

List B. In the place protected from light and moisture, at a temperature not over 25 ºС. To store in the place, unavailable to children. A period of validity - 2 years. Not to apply after the termination of the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of 10 mg and 20 mg in a blister strip packaging No. 10 x 3.