Zokor

Zokor – hypolipidemic drug.

Form of release and structure

Is issued in the form of tablets, coated: oval, smooth on the one hand, on other party – an engraving of "MSD 735" (a tablet of light pink color) or an engraving of "MSD 740" (a tablet of yellowish-brown color) (on 14 pieces in blisters, 1 or 2 blisters in a cardboard pack).

Active ingredient – симвастатин:

• 1 tablet of light pink color – 10 mg;
• 1 tablet of yellowish-brown color – 20 mg.

Excipients: ascorbic acid, butylhydroxyanisole, cellulose microcrystallic, lactoses monohydrate, starch prezhelatinizirovanny, citric acid, magnesium stearate.

Structure of a cover: hydroxypropyl cellulose, talc, methylhydroxypropyl cellulose, titanium dioxide, dyes ferrous oxide yellow and ferrous oxide red.

Indications to use

Zokor appoint to patients with the coronary heart disease (CHD) or predisposition to this disease, and also patients with high risk of development of an ischemic heart disease (including in the presence of a lipidemia), for example, a sick diabetes mellitus, to patients with diseases of peripheral vessels, a stroke or other cerebrovascular diseases in the anamnesis. Drug use purpose:

• Decrease in risk of mortality as a result of an ischemic heart disease;
• Reduction of risk of development of serious coronary or vascular complications, such as stroke, not fatal myocardial infarction, coronary death;
• Decrease in risk of hospitalization concerning stenocardia attacks;
• Reduction of probability of an operative measure due to the need of recovery of a peripheral blood-groove or other types of not coronary revascularization.

To also listed categories of patients drug is appointed in case of need by carrying out operation of revascularization.

Besides, Zokor appoint at a hypercholesterolemia – as addition to a diet in cases when only dietary food and other non-drug methods of treatment are not enough. Drug use purpose:

• Treatment of a lipidemia of the IV type according to Fredrikson's (gipertriglitseridemiya) classification;
• Therapy of primary lipidemia of the III type according to Fredrikson's (disbetalipoproteinemiya) classification;
• Decrease in the increased level of the general cholesterol, cholesterol of lipoproteins of the low density (LPNP), apolipoprotein B and triglycerides;
• Increase in cholesterol of lipoproteins of the high density (LPVP) at patients with primary hypercholesterolemia, including with a lipidemia of IIa of type on Fredrikson's classification (a heterozygous family hypercholesterolemia) or a lipidemia of IIb of type according to Fredrikson's classification (mixed by a hypercholesterolemia);
• Decrease in a ratio of level of the general cholesterol in relation to LPVP cholesterol, and also LPNP cholesterol to LPVP cholesterol;
• Decrease in the increased level of the general cholesterol, LPNP cholesterol and apolipoprotein B at patients with a homozygous family hypercholesterolemia (in addition to a diet and other methods of treatment).

At patients with a diabetes mellitus Zokor reduces risk of development of peripheral complications of vascular genesis (including probability of developing of trophic ulcers, carrying out operation of revascularization and amputation of the lower extremities).

At patients with the coronary heart disease which is followed by the increased content of cholesterol, drug allows to reduce risk of development of coronary atherosclerosis, including emergence of complications and new damages.

Contraindications

Absolute:

• Permanent increase in level of hepatic transaminases in a blood plasma of not clear etiology;
• Active diseases of a liver;
• Pregnancy and period of its planning;
• Lactation;
• Individual hypersensitivity to drug components.

Because of insufficiency of data on safety of use of Zokora in pediatrics children are not recommended to appoint drug.

Relative:

• Rabdomioliz in the anamnesis;
• Diabetes mellitus;
• Steady increase in level of serumal transaminases (in case of exceeding of upper norm by 3 times drug is cancelled);
• Heavy renal failure (the clearance of creatinine is less than 30 ml/minute);
• Alcohol abuse.

Route of administration and dosage

Prior to Zokora's use to the patient appoint a standard hypocholesteric diet which needs to be observed throughout all course of treatment.

The daily dose of drug (from 5 to 80 mg) should be accepted in 1 reception in the evening.

During titration of a dose its increase is carried out not less than with 4 weeks intervals. The most admissible daily dose makes 80 mg.

The recommended doses:

• Patients with an ischemic heart disease or high risk of its development: on 40 mg of 1 times a day. Medicamentous therapy is begun along with a diet and physiotherapy exercises;
• Patients with a hypercholesterolemia (the development of an ischemic heart disease which is not entering into risk groups): an initial dose – 20 mg a day. In some cases (if decrease in the LPNP level more than for 45% is required) the initial dose of 40 mg can be appointed. At an easy and moderate form of a hypercholesterolemia therapy it is possible to begin 10 mg with a daily dose, in need of it gradually raise;
• Patients with a homozygous family hypercholesterolemia: on 40 mg of 1 times a day or 80 mg in 3 receptions – on 20 mg in the morning and in the afternoon and 40 mg in the evening. In this case Zokor can be appointed as monodrug or in addition to other method of therapy reducing cholesterol level (for example, LPNP a plasma exchange).

Zokor is applied in the form of monotherapy or in combination with sekvestrant of bile acids. In this case correction of its dose depending on the drugs used at the same time is required:

• Danazol, cyclosporine, gemfibrozit, other fibrata (except for a fenofibrat), Niacinum in lipidosnizhayushchy doses (> 1000 mg/days): the daily dose of Zokora makes 10 mg;
• Verapamil, Amiodaronum: the daily dose of Zokora should not exceed 20 mg.

Patients with a moderate renal failure do not have need to adjust a dose. Patients with a heavy renal failure (clearance of creatinine less than 30 ml/minute) are not recommended to exceed a daily dose of 10 mg. If such need is proved, treatment has to be carried out under especially careful medical observation.

Side effects

• Alimentary system: dyspepsia (diarrhea, nausea and vomiting); seldom – pancreatitis, jaundice, hepatitis;
• Central nervous system: вертиго, peripheral neuropathy;
• Musculoskeletal system: mialgiya; seldom – рабдомиолиз;
• Allergic and immunopathological reactions: volchanochnopodobny syndrome, Quincke's disease, rheumatic polimialgiya, increase SOE, eosinophilia, arthritis, thrombocytopenia, arthralgia, vasculitis, small tortoiseshell, dermahemia, photosensitization, short wind, fever, febricula;
• Dermatological reactions: skin rash, itch, dermatomyositis, alopecia;
• Others: myotonia, paresthesias, febricula, anemia;
• Laboratory indicators: increase in level of transaminases, alkaline phosphatase and gamma глутамилтранспептидазы, kreatinfosfokinaza.

Special instructions

As well as all inhibitors of GMG-KOA-reduktazy, Zokor can cause the myopathy which is shown such symptoms as muscular pain, morbidity or the general weakness that is followed by increase in a kreatinfosfokinaza (more than 10 times higher than an upper limit of norm). The myopathy can be shown in the form of a rabdomioliz who sometimes is followed by an acute secondary renal failure owing to a myoglobinuria and in some cases leads to a lethal outcome. The risk of development of a myopathy increases at increase in concentration in a blood plasma of the substances having an inhibiting effect concerning GMG-KOA-reduktazy.

Some medicines applied along with Zokor (especially in high doses), increase risk of development of a myopathy / рабдомиолиза.

All patients to whom appoint Zokor have to be warned about need of the urgent address to the doctor in case of muscular weakness, morbidity in muscles or any inexplicable pains. In an initiation of treatment and at each increase in a dose it is recommended to define concentration of a kreatininfosfokinaza.

In cases when planned carrying out surgical intervention is necessary, Zokor it is necessary to cancel some days before operation and to refrain from his reception in the postoperative period.

Before therapy, and further according to clinical indicators of the patient it is recommended to control functions of a liver. Need to conduct additional researches of function of a liver patients to whom increase in a dose of a simvastatin to 80 mg/days is planned, then – in 3 months after the beginning of reception of a high dose of drug, further – about 1 time in 6 months within the first year of treatment. Special attention should be paid to patients for whom the increased level of serumal transaminases is diagnosed. This category of patients needs to conduct a repeated research in the nearest future and further to conduct it regularly until the level of serumal transaminases is normalized. If level increases, especially in case of steady increase is 3 times more than the upper bound of norm, Zokor it is necessary to cancel.

Medicinal interaction

The following medicines applied along with Zokor (especially in high doses), increase risk of development of a myopathy / рабдомиолиза:

• Powerful CYP3A4 inhibitors: кларитромицин, erythromycin, телитромицин, кетоконазол, нефазодон, итраконазол, inhibitors of protease of a human immunodeficiency virus;
• Other hypolipidemic means which are not strong CYP3A4 inhibitors, but are capable to cause development of a myopathy: gemfibrozit also other fibrata (except for a fenofibrat), Niacinum (niacin) in lipidosnizhayushchy doses (> 1 g/days);
• Cyclosporine, даназол;
• Amiodaronum, verapamil;
• Diltiazem.

Simvastatin applied in a daily dose of 20-40 mg exponentiates effect of coumarinic anticoagulants and increases risk of developing of bleedings: the prothrombin time (the International Normalized Relation) increases from initial level 1,7 to 1,8 at healthy volunteers, and at patients with a hypercholesterolemia – from 2,6 to 3,4. To exclude considerable changes of this indicator, to the patients receiving coumarinic anticoagulants, it is necessary to define a prothrombin time prior to Zokora's use and periodically during an initial stage of treatment. After the indicator of MNO is stabilized, its further definition needs to be carried out bucketed, recommended for control of the patients undergoing anticoagulating therapy.

Juice of grapefruit contains at least one component which inhibits CYP3A4 and can increase contents level in a blood plasma of the drugs which are metabolized this enzyme. The use of 1 glass of juice (250 ml) in days of clinical value has no. However at consumption of large amounts of juice (more than 1 liter a day) during therapy by Zokor the plasma level of activity of inhibitors of GMG-KOA-reduktazy considerably increases. For this reason during treatment it is not necessary to use large volumes of grapefruit juice.

Terms and storage conditions

To store at a temperature up to 30 ºC in the place unavailable to children.

Period of validity – 2 years.