Vazostat-Zdorovye, tab. of 10 mg No. 10Õ3/tab. 20 of mg No. 10х3

General characteristics. Structure:

International and chemical names: simvastatin; 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-2 (-тетрагидро-4-гидрокси-6-оксо-2Н-пиран-2-ил) ethyl-1-naftalenil-2,2-dimetilbutanoat;
main physical and chemical properties: tablets of a round form with a biconvex surface, coated, from light yellow till yellow color with a nacreous shade; structure: 1 tablet contains a simvastatin (in terms of 100% substance) – 10 mg or 20 mg; excipients: butylhydroxyanisole, ascorbic acid, citric acid monohydrate, tselaktoz, aerosil, potato starch, magnesium stearate, gipromelloz (gidroksipropilmeliltsellyuloz), кандурин (silver gloss), macrogoal 4000 (polyethyleneglycol 4000), titanium dioxide, Sepispers Dry Yellow R dye.

Pharmacological properties:

Pharmacodynamics. Drug korrigirut lipidic exchange, representing to itself pro-medicine. At oral administration it is hydrolyzed with formation of an active metabolite which inhibits 3-гидрокси-3-метил-глютарил-КоА-редуктазу (HMG-Co), the enzyme catalyzing reaction of formation of a mevalonat with HMG-Co. Because conversion of HMG-Co 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. Drug reduces the increased plasma cholesterol level, concentration of lipoproteins of the low density (LPNP) and lipoproteins of very low density (LPONP), slightly increases the maintenance of lipoproteins of the high density (LPVP). As a result the ratio of LPVP and LPNP increases and cholesterol (LPVP) decreases. Drug reduces concentration of triglycerides. At a heterozygous family and single hypercholesterolemia, and also at the mixed lipidemias when the main disturbance is increase in level of cholesterol, drug considerably reduces concentration of the general cholesterol and LPNP. Vazostat-Zdorovye active at inefficiency of a dietotherapy and other non-drug methods of treatment. Long reception of 20-40 mg/days at patients with a hypercholesterolemia and an ischemic heart disease reduces progressing of atherosclerotic defeat of coronary arteries. The beginning of effect of drug is noted in two weeks, the maximum therapeutic effect – in 4-6 weeks after an initiation of treatment by drug. Action remains at treatment continuation. At the therapy termination the content of cholesterol is returned to initial level.

Pharmacokinetics. Drug at oral administration is well absorbed from a GIT (about 85%). Concentration of drug and its metabolites which are formed generally in a liver reaches a maximum in a blood plasma in 4 hours and decreases by 90% in 12 hours. Simvastatin and products of his biotransformation for 95% contact proteins of plasma. Drug is removed with bile (about 85%) and with urine (13%).

Indications to use:

Primary hypercholesterolemia, the combined hypercholesterolemia and gipertriglitseridemiya, and also giperlipoproteinemiya which does not give in to correction by special diets and an exercise stress. At the coronary heart disease (CHD) - prevention of a myocardial infarction, decrease in risk of development of a stroke and passing disturbances of cerebral circulation, delay of progressing of coronary atherosclerosis.

Route of administration and doses:

Usually initial dose makes 10 mg/days of 1 times in the evening. Drug is effective both in the form of monotherapy, and in a combination with sekvestrant of bile acids. The mode of dosing and term of treatment are established individually. 
At an easy or moderate hypercholesterolemia the initial dose makes 5 mg/days. If necessary the dose can be increased, but not earlier, than in 4 weeks of treatment; maximum daily dose of 80 mg. If the maintenance of LPNP less than 75 mg/dl (1,94 mmol/l), and the content of the general cholesterol – less than 140 mg/dl (3,6 mmol/l), then a dose of drug it is necessary to reduce.
At an ischemic heart disease initial dose of 20 mg/days of 1 times in the evening. If necessary the dose is increased by each 4 weeks to 40 mg/days. Correction of the mode of dosing in case of need should be carried out as and at a hypercholesterolemia. At patients with the expressed renal failures (clearance of creatinine less than 30 ml/min.) it is necessary to estimate carefully expediency of purpose of drug in the dose exceeding 10 mg/days. As drug is removed by kidneys in a small amount, patients have no need for change of a dose with moderately expressed renal failures. At the patients accepting cyclosporines, fibrata, niacinamide, the maximum daily dose of drug makes 10 mg/days

Features of use:

Before administration of drug appoint a standard hypocholesteric diet which should adhere also during treatment. 
To appoint with care the patient who is abusing alcohol and/or having in the anamnesis of a disease of a liver.
Before the beginning, and also during a course of treatment drug it is necessary to conduct researches of functions of a liver which repeat each half a year. During treatment by drug development tranzitorny moderated (less than by 3 times) increases in the activity of transaminases which is proceeding asymptomatically and not demanding drug withdrawal is possible.
To the patients accepting симвастатин in a daily dose of 80 mg, function of a liver is controlled 1 time in 3 months. When the expressed and steady increase in activity of transaminases is observed (more than by 3 times), treatment by drug needs to be stopped. 
The patient with the mialgiya raised by a myesthesia, weakness and/or the expressed increase in activity of KFK treatment with drug is also stopped.
Use of drug should be stopped immediately in the presence of a myopathy or other risk factors (simultaneous use of tsitostatik, fibrat, high doses of Niacinum and antifungal drugs) which can contribute to development of a renal failure owing to a rabdomioliz.
Women of childbearing age who accept drugs of a simvastatin have to avoid conception. If in the course of treatment pregnancy is diagnosed, administration of drug needs to be stopped, and the woman has to be warned about possible danger to a fruit. 

Side effects:

From the alimentary system: abdominal pain, lock, meteorism, nausea, diarrhea, dyspepsia, pancreatitis, vomiting, hepatitis, jaundice; perhaps expressed and steady increase in activity of hepatic transaminases (more than by 3 times exceeding an upper limit of norm), and also the alkaline phosphatase (AP).
From the central and peripheral nervous system: headache, dizziness, muscular spasms, paresthesias, peripheral neuropathy.
Allergic reactions: seldom - a Quincke's disease, a volchanochnopodobny syndrome, a rheumatic polimialgiya, a vasculitis, thrombocytopenia, an eosinophilia, increase SOE, arthritis, urticaria, a photosensitization, fever, a dermahemia, an asthma.
Dermatological reactions: skin rash, itch, alopecia.
Other: adynamy, mialgiya, anemia, рабдомиолиз; in rare instances – a myopathy.

Interaction with other medicines:

Drug strengthens effect of indirect anticoagulants. Cytostatics, итраконазол, the fibrata, high doses of niacin applied along with simvastatiny increase risk of development of a myopathy. 

Contraindications:

Hypersensitivity to drug components, a liver failure, a superactivity of hepatic transaminases, pregnancy, the feeding period a breast, children's age up to 18 years.

Overdose:

It was reported about several cases of overdose by drugs of a simvastatin, at the same time at one of patients any specific symptoms are not revealed. Most accepted dose – 450 mg. Treatment at overdose: to wash out a stomach, to accept absorbent carbon, control of the vital functions of an organism, including function of kidneys and a liver, and also the KFK level in blood serum.

Storage conditions:

To store in the dry, protected from light place at a temperature from 15 °C to 30 °C. To store in the place, unavailable to children.

Period of validity – 2 years.

Issue conditions:

According to the recipe

Packaging:

Po10 or 30 tablets in a blister strip packaging; No. 10х3, No. 30 in a pack.