Simvor

General characteristics. Structure:

For a dosage of 5 mg
Active agent: симвастатин 5 mg.
Excipients: lactose - 36,111 mg, prezhelatinizirovanny starch - 3.75 mg, cellulose microcrystallic - 50 mg, the hypro rod low-replaced - 4 mg, butylhydroxyanisole - 0,1 mg, magnesium stearate - 1 mg.
Cover material: опадрай yellow OY-LS-52901 - 4 mg, water - q.s.
Опадрай yellow OY-LS-52901: a gipromeloza - 34,95 mg, lactoses monohydrate - 27,18 mg, titanium dioxide - 24,663 mg, a macrogoal of 400 - 9,7 mg, sodium citrate - 2,93 mg, ferrous oxide yellow - 0,577 mg.
For a dosage of 10 mg
Active agent: симвастатин 10 mg.
Excipients: lactose - 31,072 mg, prezhelatinizirovanny starch - 3.75 mg, cellulose microcrystallic - 50 mg, the hypro rod low-replaced - 4 mg, butylhydroxyanisole - 0,1 mg, magnesium stearate - 1 mg.
Cover material: опадрай light pink OY-LS-54901 - 4 mg, water - q.s.
Опадрай light pink OY-LS-54901: a gipromeloza - 34,95 mg, lactoses monohydrate - 27,18 mg, titanium dioxide - 25,207 mg, a macrogoal of 400 - 9,7 mg, sodium citrate - 2,93 mg, ferrous oxide red - 0,033 mg.
For a dosage of 20 mg
Active agent: симвастатин 20 mg.
Excipients: lactose - 62,143 mg, prezhelatinizirovanny starch - 7,5 mg, cellulose microcrystallic - 100 mg, the hypro rod low-replaced - 8 mg, butylhydroxyanisole - 0,2 mg, magnesium stearate - 2 mg.
Cover material: опадрай brown OY-LS-56504 - 8 mg, water - q.s.
Опадрай brown OY-LS-56504: a gipromeloza - 34,95 mg, lactoses monohydrate - 27,18 mg, titanium dioxide - 24,275 mg, a macrogoal of 400 - 9,7 mg, sodium citrate - 2,93 mg, ferrous oxide yellow - 0,689 mg, ferrous oxide red - 0,276 m
For a dosage of 40 mg
Active agent: симвастатин 40 mg.
Excipients: lactose - 124,286 mg, prezhelatinizirovanny starch - 15 mg, cellulose microcrystallic - 200 mg, the hypro rod low-replaced - 16 mg, butylhydroxyanisole - 0,4 mg, magnesium stearate - 4 mg.
Cover material: опадрай pink OY-LS-54902 - 16 mg, water - q.s.
Опадрай pink OY-LS-54902: a gipromeloza - 34,95 mg, lactoses monohydrate - 27,18 mg, titanium dioxide - 23,99 mg, a macrogoal of 400 - 9,7 mg, sodium citrate - 2,93 mg, ferrous oxide of red-1,25 mg.

Description
Tablets of 5 mg: yellow biconvex tablets, an oval form, film coated with an engraving of "SST" on one party and "5" on other party.
Tablets of 10 mg: pinkish-white color biconvex tablets of an oval form, film coated with an engraving of "SST" on one party and "10" on other party.
Tablets of 20 mg: light pink biconvex tablets of an oval form, film coated with an engraving of "SST" on one party and "20" on other party. Tablets of 40 mg: pink biconvex tablets of an oval form, film coated with an engraving of "SST" on one party and "40" on other party.

Pharmacological properties:

Pharmacokinetics. Absorption of a simvastatin — high. After intake the maximum concentration in a blood plasma is reached approximately in 1,3–2,4 h and decreases by 90% in 12 h. Linkng with proteins of plasma makes 95%.
It is metabolized in a liver, has effect of the first passing through a liver (it is hydrolyzed with formation of active derivative — beta hydroxyacids; also other active, and also inactive metabolites are found). T1/2 of active metabolites makes 1,9 h.
It is removed preferential with a fecal masses (60%) in the form of metabolites. About 10-15% are removed by kidneys in an inactive form.

Pharmacodynamics. The hypolipidemic means received in the synthetic way from Aspergillus terreus fermentation product. The inactive lactone, in an organism is exposed to hydrolysis with formation of hydroxyacid derivative.
The active metabolite inhibits 3-гидрокси-3-метил-глутарил-КоА-редуктазу (GMG-KOA-reduktazu), the 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 synthetic processes in an organism.
Reduces the content (TG), LPNP triglycerides, lipoproteids of very low density (LPONP) and the general cholesterol in plasma (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 LPVP and reduces a ratio of LPNP/LPVP and the general cholesterol / LPVP.
The effect is shown in 2 weeks from the beginning of reception, the maximum therapeutic effect is reached in 4–6 weeks. Action remains at treatment continuation; at the therapy termination the content of cholesterol gradually is returned to initial level (prior to treatment).

Indications to use:

Hypercholesterolemia

- primary hypercholesterolemia (IIA and IIb type) 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 combined hypercholesterolemia and a gipertriglitseridemiya, not adjusted by a special diet and an exercise stress.
Coronary heart disease:
- for prevention of a myocardial infarction, for reduction of risk of death, reduction of risk of cardiovascular disturbances (a stroke or tranzitorny ischemic attacks), delay of progressing of atherosclerosis of coronary vessels, reduction of risk of procedures of revascularization.

Route of administration and doses:

Inside, 1 time a day in the evening, washing down with enough water, irrespective of meal.
Prior to treatment by the drug Simvor® the patient should appoint a standard hypocholesteric diet which has to be observed during all course of treatment.
The recommended drug Simvor® dose for treatment of a hypercholesterolemia varies from 10 to 80 mg of 1 times for about days in the evening. The recommended initial dose of drug for patients with a hypercholesterolemia, makes 10 mg.
The maximum daily dose — 80 mg.
Changes (selection) of a dose should be carried out bucketed to 4 weeks. At most of patients the optimum effect is reached at administration of drug in doses to 20 mg/days.
At patients with a homozygous hereditary hypercholesterolemia the recommended daily dose of the drug Simvor® 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; 40 mg — in the evening).
At treatment of patients with an ischemic heart disease or high risk of development of an ischemic heart disease, effective doses of the drug Simvor® make 20–40 mg/days. Therefore the recommended initial dose at such patients — 20 mg/days. Change (selection) of a dose should be carried out bucketed to 4 weeks, if necessary it is possible to increase a dose to 40 mg/days. If the maintenance of LPNP less than 75 mg/dl (1,94 mmol/l), content of the general cholesterol less than 140 mg/dl (3,6 mmol/l), a dose of drug needs to be reduced.
Or having a renal failure of easy or moderate extent of changes of a dosage of drug it is not required to patients of advanced age.
To patients with a chronic renal failure (creatinine Cl less than 30 ml/min.) or receiving cyclosporine, fibrata, даназол, gemfibrozit or other fibrata (except a fenofibrat), Niacinum in the doses reducing the maintenance of lipids (≥1 g/days), most recommended dose of the drug Simvor® should not exceed 10 mg/days.
The daily dose of the drug Simvor® at the patients accepting along with it Amiodaronum or verapamil should not exceed 20 mg.

Features of use:

At the beginning of therapy by the drug Simvor® 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). At increase in doses 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 трансминаз (by 3 times in comparison with initial level) administration of drug of Simvor® should be stopped.
Симвор®, as well as other inhibitors of GMG-KOA-reduktazy, 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, an injury, heavy metabolic disturbances).
Cancellation of hypolipidemic means during pregnancy has no significant effect on results of prolonged treatment of primary hypercholesterolemia.
Because inhibitors of GMG-KOA-reduktazy slow down cholesterol synthesis, and cholesterol and other products of its synthesis play an essential role in fetation, including synthesis of steroids and cellular membranes, симвастатин can make an adverse effect on a fruit at appointment to his pregnant women (women of reproductive age have to avoid conception). If in the course of treatment there is pregnancy, drug has to be cancelled, and the woman is warned about possible danger to a fruit.
Use of the drug Simvor® is not recommended at the women of childbearing age who are not using contraceptive means.
At patients with the lowered function of a thyroid gland is (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 at first therapy of the basic disease which caused a hypercholesterolemia.
Симвор® with care appoint to persons who abuse alcohol and/or have 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.
The concomitant use of grapefruit juice can strengthen degree of manifestation of the by-effects connected with administration of drug of Simvor® therefore it is necessary to avoid their concomitant use.
At patients with a mialgiya, a myasthenia and/or the expressed increase in activity of KFK treatment by drug is stopped. Симвор® it is not shown when there is a gipertriglitseridemiya I, IV and V types.
Treatment by the drug Simvor® can cause the myopathy leading to a rabdomioliz and a renal failure. The risk of developing of this pathology increases at the patients receiving along with the drug Simvor® one or a little from the following HP: (gemfibrozit) fibrata, cyclosporine, нефазадон, macroleads (erythromycin, кларитромицин), antifungal means from group of azoles (кетоконазол, итраконазол) and HIV inhibitors of proteases (ритонавир). The risk of development of a myopathy increases also at patients with a heavy renal failure.
All patients beginning therapy with the drug Simvor® 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 drug has to be immediately stopped if the myopathy is diagnosed or is supposed.
For diagnosing of development of a myopathy it is recommended to take measurements of size KFK regularly.
At treatment by the drug Simvor® increase of maintenance of serumal KFK is possible that should be considered at differential diagnosis of pains behind a breast. As criterion of drug withdrawal serves increase in maintenance of KFK in blood serum more than by 10 times of rather upper bounds of norm.
It 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 drug needs to be accepted as soon as possible. If came time of reception of the following dose, a dose not to double.
To patients with a heavy renal failure treatment is carried out under control of function of kidneys.
Duration of use of drug is defined by the attending physician individually.
Influence on ability to drive the car and work with mechanisms. About adverse influence of the drug Simvor® on ability to drive the car and work with mechanisms it was not reported.

Side effects:

Alimentary system: abdominal pains, a lock, a meteorism, nausea, diarrhea, pancreatitis, vomiting, hepatitis, increase in activity of liver enzymes, ShchF and kreatinfosfokinaza (KFK) are possible.
Nervous system and sense bodys: asthenic syndrome, headache, dizziness, sleeplessness, muscular spasms, paresthesias, peripheral neuropathy, sight vagueness, disturbance of flavoring feelings.
Allergic and immunopathological reactions: Quincke's disease, rheumatic polimialgiya, vasculitis, thrombocytopenia, increase SOE, fever, arthritis, urticaria, photosensitization, dermahemia, inflows, asthma. volchanochnopodobny syndrome, eosinophilia.
Dermatological reactions: seldom skin rash, itch, alopecia, dermatomyositis.
From a musculoskeletal system: myopathy, mialgiya, myotonia, weakness; seldom — рабдомиолиз.
Others: anemia, heartbeat, an acute renal failure (owing to a rabdomioliz), decrease in a potentiality.

Interaction with other medicines:

Cytostatics, antifungal means (кетоконазол, итраконазол), fibrata, high doses of niacin, immunodepressants, erythromycin, кларитромицин, телитромицин, inhibitors of HIV proteases, нефазодон increase risk of development of a myopathy.
Cyclosporine or даназол: the risk of development of a myopathy / рабдомиолиза increases at joint purpose of cyclosporine or a danazol with high doses of a simvastatin.
Other hypolipidemic means capable to cause development of a myopathy: the risk of development of a myopathy increases at joint purpose of other hypolipidemic means which are not powerful CYP3A4 inhibitors, but are capable to cause a myopathy in the conditions of monotherapy, such as gemfibrozit also other fibrata (except a fenofibrat), and also Niacinum (niacin) in a dose of ≥1 g/days.
Amiodaronum and verapamil: the risk of development of a myopathy increases at joint reception of Amiodaronum or verapamil with high doses of a simvastatin.
Diltiazem: 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 (for example фенпрокумон, warfarin) and increases risk of developing of bleedings that demands monitoring procedure of indicators of coagulability of blood prior to treatment, and also regular control during an initial stage of therapy. As soon as the stable level of an indicator of PV or MNO is reached, its further control should be carried out bucketed, recommended for the patients receiving therapy by anticoagulants. At change of a dosage or the termination of reception of a simvastatin it is also necessary to carry out control of PV or MNO according to the above scheme.
Therapy simvastatiny does not cause changes of PV and risk of bleedings in the patients who are not accepting anticoagulants.
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 syndrome is noted).
Juice of grapefruit contains one or more components which inhibit CYP3A4 and can increase concentration in a blood plasma of the means which are metabolized CYP3A4.
Increase in activity of inhibitors of GMG-KOA-reduktazy after the use 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:

- Hypersensitivity to a simvastatin or to other components of drug, and also to other drugs of a statinovy row (GMG-KOA-reduktazy inhibitors) in the anamnesis;
- liver diseases in an active phase, permanent increase in activity of liver enzymes of not clear etiology;
- porphyria;
- diseases of skeletal muscles (myopathy);
- age up to 18 years (efficiency and safety are not established).

With care:
the patients abusing alcohol;
patients after organ transplantation which carries out therapy by immunodepressants (in connection with the increased risk of emergence of a rabdomioliz and a renal failure);
states which can lead to development of the expressed insufficiency of function of kidneys (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);
patients with the lowered or raised tone of skeletal muscles of not clear etiology;
epilepsy.
Use at pregnancy and feeding by a breast
Симвор® it is contraindicated to pregnant women. There are several messages on development of anomalies in newborns which mothers accepted симвастатин.
The women of childbearing age accepting симвастатин have to avoid conception. If in the course of treatment pregnancy nevertheless occurred, Simvor® has to be cancelled, and the woman has to be warned about possible danger to a fruit.
Data on allocation of a simvastatin with maternal milk are absent. In need of purpose of the drug Simvor® during feeding by a breast 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.

Overdose:

In one of several known cases of overdose (most accepted dose — 450 mg) specific symptoms were not revealed.
Treatment: induction of vomiting, purpose of absorbent carbon. Symptomatic therapy. It is necessary to control functions of a liver and kidneys, the KFK level 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 administration of drug and to enter to the patient diuretic and sodium bicarbonate (in/in infusion). If necessary the hemodialysis is shown.
Rabdomioliz can cause a hyperpotassemia which can be eliminated in/in introduction of Calcii chloridum and calcium of a gluconate, infusion of glucose with insulin, use of potassium ion exchangers or in hard cases — by means of a hemodialysis.

Storage conditions:

To store in the dry place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 2 years. Not to use after the termination of the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets coated 5 mg, 10 mg, 20 mg, 40 mg. 10 tablets in the blister from aluminum foil and PVC of a film. 1, 3 or 10 blisters with the application instruction in a cardboard pack.