Pharmacological properties

Drug korrigirut lipidic exchange, representing pro-medicine. at oral administration it is hydrolyzed with formation of an active metabolite which inhibits 3-hydroxy-3-methyl-glyutaril-koa-reductase (nmg-co), the enzyme catalyzing reaction of formation of the mevalonat with hmg-co. because conversion of hmg-co in mevalonat represents an early stage of synthesis hs, the primeniye of a simvastatin does not cause accumulation in an organism of potentially toxic sterols. medicament reduces the increased level hs blood plasma, concentration of LDL and lponp, contents lpvp slightly increases. as a result the ratio lpvn and LDL raises and decreases hs. medicament reduces concentration of triglycerides. at heterozygous family and single hyper cholesterinemias and also at the mixed lipidemias when the main disturbance is increase in level hs, medicament considerably reduces concentration of the general hs and LDL. vazostat-health it is active at inefficiency of a dietotherapy and other non-medicament methods of treatment. long reception of 20-40 mg/days at patients with a hypercholesterolemia and an ischemic heart disease reduces progressing of atherosclerotic damage of coronary arteries. the beginning of effect of medicament is noted already in 2 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 contents hs is returned to initial level.

in a GIT (about 85%). Concentration of medicament and its metabolites which are formed generally in a liver reaches a maximum in blood plasma in 4 h and Simvastatin decreases by 90% in 12 h and products of his biotransformation for 95% contact proteins of blood plasma. Drug is removed with bile (about 85%) and urine (13%).

Indication

Primary hypercholesterolemia, the combined hypercholesterolemia and a gipertriglitseridemiya and also the giperlipoproteinemiya which is not giving in to correction by special diets and physical activity. at an ischemic heart disease — prevention of a myocardial infarction, reduction of risk of development of a stroke and passing disturbances of cerebral circulation, delay of progressing of coronary atherosclerosis.

Use

Usually initial dose makes 10 mg/days of 1 times in the evening.

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 raised, but not earlier than in 4 weeks of treatment; maximum daily dose of 80 mg. If the content of LDL is lower than 75 mg/dl (1.94 mmol/l), and keeping of the general of the XC less than 140 mg/dl (3.6 mmol/l), then the dose of medicament needs to be lowered.

At an ischemic heart disease an initial dose of 20 mg/days of 1 times in the evening. If necessary the dose is raised by each 4 weeks to 40 mg/days. Correction of the mode of dosing in case of need should be carried out as well as at a hypercholesterolemia. At patients with the profound renal failures (clearance of creatinine less than 30 ml/min.) it is necessary to estimate carefully expediency of prescribing of medicament in the dose exceeding 10 mg/days. As medicament is removed by kidneys in a small amount, patients have no need for change of a dose with moderate renal failures. At the patients accepting cyclosporines, fibrata, niacinamide the maximum daily dose of medicament makes 10 mg/days

Contraindication

Hypersensitivity to medicament components, a liver failure, superactivity of hepatic transaminases, the period of pregnancy and feeding by a breast, age up to 18 years.

Side effects

from digestive system: abdominal pain, constipation, meteorism, nausea, diarrhea, dyspepsia, pancreatitis, vomiting, hepatitis, jaundice; perhaps significant and steady increase in activity of hepatic transaminases (more than by 3 times exceeding an upper limit of norm) and also shchf.

from the central and peripheral nervous system: headache, dizziness, muscular spasms, paresthesias, peripheral neuropathy.

Allergic reactions: seldom — a Quincke's disease, a volchanochnopodobny syndrome, rheumatic polymyalgia, a vasculitis, thrombocytopenia, an eosinophilia, increase SOE, arthritis, a small tortoiseshell, a photosensitization, fever, a dermahemia, an asthma.

Dermatological reactions: skin rash, itching, alopecia.

Other: asthenia, myalgia, anemia, rhabdomyolysis; in rare instances — a myopathy.

Special instructions

before administration of medicament 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 medicament it is necessary to conduct researches of functions of a liver which repeat each half a year. During medicament treatment the development tranzitorny moderated (less than by 3 times) increases in the activity of transaminases which is proceeding asymptomatically and not demanding medicament withdrawal is possible. To the patients accepting simvastatin in a daily dose of 80 mg, function of a liver is controlled 1 time in 3 months. In those cases when the significant and steady increase in activity of transaminases is observed (more than by 3 times), medicament treatment should be stopped.

Sick with myalgia raised by myesthesia, weakness and/or the significant increase in activity of KFK medicament treatment also is stopped. Use of medicament should be stopped immediately in the presence of a myopathy or other risk factors (simultaneous use of tsitostatik, fibrat, Niacinum and antifungal medicaments in high doses) which can contribute to development of a renal failure owing to a rhabdomyolysis.

Woman of reproductive age, the taking medicaments of a simvastatin, should not plan pregnancy. If in the course of treatment the pregnancy is diagnosed, administration of medicament needs to be stopped, and the woman has to be warned about possible danger to a fruit.

Interaction

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

Overdose

It was reported about several cases of overdose by medicaments 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 activated carbon; control of the vital functions of an organism, including function of kidneys and a liver and also level kfk in blood serum.

Storage conditions

B the dry, protected from light place at a temperature of 15-30 °C.