Simvageksal

General characteristics. Structure:

Симвагексал®, tablets coated on 5 mg:
Active agent: симвастатин 5 mg
Excipients: Starch, lactoses monohydrate, cellulose microcrystallic, butylhydroxyanisole, ascorbic acid, citric acid monohydrate, magnesium stearate, gipromelloz, talc, titanium dioxide, ferrous oxide yellow.

Симвагексал®, tablets coated on 10 mg:
Active agent: симвастатин 10 mg
Excipients: Starch, lactoses monohydrate, cellulose microcrystallic, butylhydroxyanisole, ascorbic acid, citric acid monohydrate, magnesium stearate, gipromelloz, talc, titanium dioxide, ferrous oxide red, ferrous oxide yellow.

Симвагексал®, tablets coated on 20 mg:
Active agent: симвастатин 20 mg
Excipients: Starch, lactoses monohydrate, cellulose microcrystallic, butylhydroxyanisole, ascorbic acid, citric acid monohydrate, magnesium stearate, gipromelloz, talc, titanium dioxide, ferrous oxide red, ferrous oxide yellow.

Симвагексал®, tablets coated on 30 mg:
Active agent: симвастатин 30 mg
Excipients: Starch, lactoses monohydrate, cellulose microcrystallic, butylhydroxyanisole, ascorbic acid, citric acid monohydrate, magnesium stearate, gipromelloz, talc, titanium dioxide.

Симвагексал®, tablets coated on 40 mg:
Active agent: симвастатин 40 mg
Excipients: Starch, lactoses monohydrate, cellulose microcrystallic, butylhydroxyanisole, ascorbic acid, citric acid monohydrate, magnesium stearate, gipromelloz, talc, titanium dioxide, ferrous oxide red.

Pharmacological properties:

The hypolipidemic means received in the synthetic way from Aspergillus terreus fermentation product is an 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 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 content in plasma of triglycerides (TG), lipoproteids of the low density (LPNP), lipoproteids of very low density (LPONP) 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 lipoproteids of the high density (LPVP) and reduces a ratio of LPNP / LPVP and the general cholesterol / LPVP.
The beginning of manifestation of effect – 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.

Pharmacokinetics. Absorption of a simvastatin - high. After intake the maximum concentration in a blood plasma is reached approximately in 1,3 – 2,4 hours and decreases by 90% in 12 hours. Linkng with proteins of a blood plasma makes about 95%.
It is metabolized in a liver, has effect of "the first passing" through a liver (it is hydrolyzed with formation of active derivative: a beta – hydroxyacid, also other active, and also inactive metabolites are found). The elimination half-life of active metabolites makes 1,9 hours.
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.

Indications to use:

Hypercholesterolemia:
primary hypercholesterolemia (lla and llb type) at inefficiency of a dietotherapy with the low content of cholesterol and other non-drug actions (an exercise stress and weight reduction of a body) at patients with the increased risk of developing of coronary atherosclerosis;
the combined giperkholestetrinemiya and the gipertriglitseridemiya which are not giving in to correction by a special diet and an exercise stress.

Coronary heart disease:
prevention of a myocardial infarction (secondary prevention of a myocardial infarction) at patients with the increased cholesterol level (> 5,5 mmol/l).

Route of administration and doses:

Симвагексал® it is necessary to accept in 1 times a day in the evening, washing down with enough water.

Hypercholesterolemia:
Depending on hypercholesterolemia degree of manifestation an initial dose - from 5 to 10 mg a day. The size of a dose is established on the basis of results of the sizes of level of cholesterol in plasma received with an interval of, at least, 4 weeks. The usual day dose makes 40 mg of a simvastatin. At insufficient efficiency and with cardiovascular risk increase in a dose as much as possible before reception on 80 mg a day is allowed.

Coronary heart disease:
The initial dose makes 20 mg. If necessary the dose is gradually increased by each 4 weeks to 40 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), a dose of drug it is necessary to reduce.
For patients with a chronic renal failure (clearance of creatinine less than 30 ml/min.) or accepting at the same time cyclosporine, fibrata or niacinamide, the initial dose makes 5 mg, and the most admissible daily dose - 10 mg.
Against the background of immunodepressive therapy the recommended initial dose – 5 mg a day, the maximum daily dose makes 5 mg a day.

Features of use:

At the beginning of therapy simvastatiny perhaps passing increase in level of hepatic enzymes (serumal transaminase).
Before therapy and further regularly to conduct a research of function of a liver (to control activity of "hepatic" transaminases each 6 weeks within the first 3 months, then each 8 weeks within the remained first year, and then once a year), and also 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 of transaminases (by 3 times in comparison with initial level) reception of Simvageksala® should be stopped.

Симвагексал®, as well as other GMG-Co-A-inhibitors of reductase, 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).
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 холестетрин 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 occurred pregnancy, drug has to be cancelled, and the woman is warned about possible danger to a fruit.
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 therapy of the cornerstone disease at first.
Patients have to report to the doctor about any manifestations from muscular system. For diagnosing of development of a myopathy it is recommended to take measurements of size KFK regularly.

Симвагексал® 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 reception of СимвагексалаÒ 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 with drug is stopped. СимвагексалÒ it is not shown when there is a gipertriglitseridemiya I, IV and V types. 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.

Side effects:

Alimentary system: abdominal pains, a lock, a meteorism, nausea, diarrhea dyspepsia, pancreatitis, vomiting, hepatitis, increase in activity of hepatic transaminases, an alkaline phosphokinase 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: seldom Quincke's disease, rheumatic polimialgiya, vasculitis, thrombocytopenia, increase SOE, fever, arthritis, urticaria, photosensitization, dermahemia, inflows, asthma, volchanopodobny syndrome, eosinophilia.

Dermatological reactions: seldom skin rash, itch, alopecia.

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

Others: anemia, heartbeat, an acute renal failure (owing to a rabdomioliz), decrease in a potentiality.

Interaction with other medicines:

Cytostatics, antifungal drugs (кетоконазол, итраконазол), fibrata, high doses of niacin, immunodepressants, erythromycin, кларитромицин, inhibitors of proteases increase risk of development of a rabdomioliz.
Leads to strengthening of effect of peroral anticoagulants (e.g., фенпрокумон, warfarin) and increases risk of developing of bleedings that demands need of monitoring procedure of coagulability of blood prior to treatment and in regular time intervals.
Increases digoxin level in a blood plasma.
Colestyraminum and колестипол reduce bioavailability, use of a simvastatin is possible in 4 hours after reception of the specified drugs, at the same time the additive effect is noted.

Contraindications:

- Hypersensitivity to a simvastatin or to other components of drug, and also to other drugs of a statinovy row (HMG-CoA-reductases inhibitors) in the anamnesis;
- liver failure, acute diseases of a liver, permanent increase in activity of hepatic transaminases of not clear etiology;
- disturbance of formation of red blood cells (porphyria);
- diseases of skeletal muscles (myopathy);
- a concomitant use of a ketokonazol, an itrakonazol (antifungal drugs of system use), means for treatment of HIV infection.

With care appoint the patient abusing alcohol, to 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); at states which can lead to development of the expressed insufficiency of function of kidneys, such as arterial hypertension, acute infectious diseases of a heavy current, the expressed metabolic and endocrine disturbances, disturbances vodno – electrolytic balance, surgical interventions (including dental) or injuries; to patients with the lowered or raised tone of skeletal muscles of not clear etiology; at epilepsy; age up to 18 years (safety and efficiency of use are not established).

Pregnancy and period of feeding:
It is not necessary to accept Simvageksal® during pregnancy. 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 administration of drug pregnancy nevertheless occurred, it is necessary to cancel reception of Simvageksala®, 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 Simvageksal's appointment women during feeding should consider that many medicines are emitted 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 the known several cases of overdose (most accepted dose of 450 mg) of specific symptoms it was not revealed.
Treatment: to cause vomiting, to accept absorbent carbon. Symptomatic therapy. It is necessary to control functions of a liver and kidneys, kreatinfosfokinaza level in blood serum.

Storage conditions:

List B. At a temperature not above 30 °C and in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets on 5; 10; 20; 30 and 40 mg, coated on 10 pieces in the blister from PVC / aluminum foil. On 1, 2, 3, 4 or 5 blisters together with the application instruction in cardboard packaging.