Вазилип®

General characteristics. Structure:

Active ingredient: 10 mg, 20 mg or 40 mg of a simvastatin.

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

The cover is film: gipromelloza, talc, propylene glycol, titanium dioxide.

Drug, corrective lipidic exchange, reducing cholesterol level.

Pharmacological properties:

Pharmacodynamics. Active agent of the drug Vazilip® is симвастатин which main effect is decrease in content of the general cholesterol and cholesterol of lipoproteins of the low density (LPNP) in a blood plasma. It is Z-gidroksi-3-metil inhibitor glutaryl of coenzyme A (GMG-KOA) - reductases, the enzyme catalyzing transformation GMG-KOA into mevalonovy acid (an early stage of synthesis of cholesterol). Simvastatin reduces concentration of the general cholesterol, cholesterol of lipoproteins of the low density (LPNP) and triglycerides. Content of cholesterol of lipoproteins of very low density (LPONP) also decreases while the content of cholesterol of lipoproteins of the high density (LPVP) moderately increases. Reduces the content of the general cholesterol and LPNP in cases of heterozygous family and single forms of a cholesterinemia, at the mixed lipidemia when the increased content of cholesterol is risk factor. Drug reduces the level of the general cholesterol and LPNP cholesterol at patients with coronary heart disease, reducing risk of a myocardial infarction and a lethal outcome for these patients.

Simvastatin also significantly reduces the content of apolipoprotein B, moderately increases concentration of LPVP cholesterol and reduces plasma concentration of triglycerides (TG). As a result of these effects of a simvastatin the ratio of the general cholesterol (GC) to LPVP (OH/LPVP) cholesterol and LPNP cholesterol to LPVN (LPNP/LPVP) cholesterol decreases.

The anti-atherosclerotic effect of a simvastatin is a consequence of impact of drug on walls of vessels and components of blood. Simvastatin changes metabolism of macrophages, oppressing activation of macrophages and destruction of atherosclerotic plaques. Drug suppresses synthesis of the isoprenoids which are growth factors at proliferation of smooth muscle cells of an internal cover of vessels. Under the influence of a simvastatin the endothelium - dependent expansion of blood vessels improves. The therapeutic effect occurs in 2 weeks, the maximum effect is observed in 4-6 weeks of treatment.

Pharmacokinetics. Simvastatin is presented in an inactive lactone form which is rather well absorbed (from 61% to 85%) from digestive tract. Bioavailability - less than 5%. After intake the maximum therapeutic concentration in a blood plasma (Stakh) is reached in 1-2 hours and decreases by 90% in 12 h. The concomitant use of food does not influence absorbability of drug. At long reception of cumulation of drug in an organism does not occur. Communication with proteins of a blood plasma - 98%.

Simvastatin is CYP3A4 substrate. It is metabolized in a liver, has effect of "the first passing" through a liver (it is generally hydrolyzed in the active form beta hydroxyacid). It is generally removed by intestines (60%) in the form of metabolites. About 13% are removed by kidneys in an inactive form. The elimination half-life of active metabolites (Тщ) makes 1,9 h.

Indications to use:

Hypercholesterolemia. Primary hypercholesterolemia or the mixed dislipidemiya (in addition to a diet and at inefficiency of other non-drug actions (an exercise stress and decrease in body weight)).

Homozygous hereditary hypercholesterolemia (in addition to a special diet and gipolshshdemichesky therapy (for example, to LPNP aferez) or at inefficiency of these measures).

Cardiovascular prevention. Reduction of cardiovascular mortality and incidence at patients with clinical displays of atherosclerotic cardiovascular diseases or a diabetes mellitus, at the normal or increased level of cholesterol and as an additional measure to correction of other risk factors and cardioprotective therapy.

Route of administration and doses:

The application instruction tells those to whom appointed Vazilip that he is accepted orally, in the evening, 1 time a day.

Usual daily dosage – 5-80 mg. As a rule, appoint 10 mg. Correction of a dosage needs to be carried out with the minimum interval of 4 weeks. The day dose should not be more than 80 mg. The maximum dosage is appointed only to people with a heavy hypercholesterolemia or the increased probability of emergence of cardiovascular complications. The application instruction of Vazilip reports that the course of treatment is defined by the specialist in each case individually, depending on what indications to use are and as the patient transfers medicine.

In case of a hypercholesterolemia it is necessary to conduct a usual hypocholesteric diet during treatment. An initial dosage in most cases – 10 mg. For more considerably LPNP cholesterol reduction the course can be begun with 20–40 mg/day.

At a homozygous hereditary hypercholesterolemia usually accept a day 40 mg or 80 mg, but in three steps (as a rule, on 20 mg in the morning and in the afternoon and 40 more mg in the evening). It is desirable to combine drug with reception of other hypolipidemic means.

For prevention of development of cardiovascular diseases in people with the increased risk of an ischemic heart disease appoint from 20 to 40 mg/days. The drug dosage which is picked up individually is reduced if the LPNP level less than 75 mg/dl and the general cholesterol is less than 140 mg/dl.

Vazilip it is possible to apply together with sekvestrant of bile acids. Patients who undergo treatment of a fibratama or niacin accept an initial dosage in 5 mg. The maximum day dose at the same time should not be more than 10 mg. And at a combination to Amiodaronum or Verapamil it is impossible to exceed a dosage in 20 mg.

At the expressed renal failure it is better not to exceed a dose in 10 mg/days. If increase in a dosage after all is necessary, the condition of the patient needs to be controlled constantly.

Features of use:

At patients with reduced 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. To patients with a heavy renal failure treatment is carried out under control of function of kidneys.

During treatment by the drug Vazilip®, women of reproductive age have to use well-tried remedies of contraception. Treatment simvastatiny, as well as other inhibitors of GMK-KOA-reduktazy, can cause the myopathy sometimes leading to a rabdomioliz with development or without renal failure in the investigation of a myoglobinuria. The risk of development of a myopathy increases at increase in a dose of a simvastatin and at patients with a heavy renal failure.

At treatment simvastatiny increase of maintenance of a serumal kreatinfosfokinaza (KFK) is possible that should be considered at differential diagnosis of pains behind a breast and after intensive exercise stresses.

Before therapy by the drug Vazilip® or increase in its dose patients have to be informed on risk of development of a myopathy and need to see immediately a doctor in case of inexplicable pain, tension or weakness in muscles, especially if it is followed by an indisposition or fever.

The KFK initial level before therapy needs to be determined in sleduyushchikhsituation:

- at elderly patients;
- at damage of kidneys;
- at a dekompensirovanny hypothyroidism;
- at the burdened family anamnesis on hereditary diseases of muscles;
- in the presence in the anamnesis of toxic impact on muscles of statines or fibrat;
- at an alcohol abuse.

It is necessary to estimate possible risk and the expected advantage and during therapy clinical monitoring against the background of therapy is recommended. If initially the KFK level is considerably increased (more than 5 times of rather upper bound of norm), measurement needs to be repeated in 5-7 days for confirmation of results. At substantial initial increase of the KFK level (more than 5 times of rather upper bound of norm) it is not recommended to appoint drug.

Prior to the beginning of and during a course of treatment the patient has to be on a hypocholesteric diet.

During treatment by the drug Vazilip® at emergence of pain in muscles, weakness or spasms it is necessary to determine the KFK level. As criterion of drug withdrawal serves increase in maintenance of KFK in blood serum more than by 5 times of rather upper bound of norm. If muscular symptoms are strongly expressed and cause discomfort, even at the KFK level less than 5 times of rather upper bound of norm, perhaps, it is necessary to stop treatment. At suspicion on a myopathy therapy needs to be stopped, regardless of the myopathy reason. If symptoms disappear, and the maintenance of KFK returned to normal level, perhaps repeated purpose of statine or alternative drug of the same class in the minimum clinically effective dose and under careful medical observation.

Therapy by the drug Vazilip® needs to be stopped temporarily some days before large surgical interventions.

To patients with a heavy renal failure treatment is carried out under control of function of kidneys.

Measures for decrease in risk of the myopathy caused by medicinal interactions

The risk of a myopathy and rabdomioliz considerably increases at simultaneous use of a simvastatin and powerful CYP3A4 inhibitors (for example, an itrakonazola, a ketokonazola, erythromycin, a klaritromitsin, a telitromitsin, inhibitors of HIV proteases, a nefazodon), gemfibrozit or cyclosporine (you watch the section "Interaction with Other Medicines"). The risk of a myopathy and rabdomioliz also increases when sharing fibrat and high doses of niacin (more than 1 g/days) or at simultaneous therapy by Amiodaronum or verapamil with high doses of a simvastatin (you watch the section "Interaction with Other Medicines"). The risk also increases a little at co-administration of diltiazem and high doses of a simvastatin (80 mg). Therefore, use of a simvastatin along with itrakonazoly, ketokonazoly, erythromycin, klaritromitsiny, telitromitsiny, inhibitors of HIV proteases and nefazodony is contraindicated (you watch the section "Contraindications"). If it is impossible to refuse therapy by the listed CYP3A4 inhibitors, it is necessary to refrain from purpose of a simvastatin. Simvastatin it is also necessary to combine with care with some other, less strong CYP3A4 inhibitors: cyclosporine, verapamil and diltiazem (you watch the section "Interaction with Other Medicines").

It is necessary to avoid a concomitant use of a simvastatin and grapefruit juice.

At the patients accepting cyclosporine gemfibrozit or high doses of niacin (more than 1 g/days), a daily dose of a simvastatin should not exceed 10 mg. Co-administration of a simvastatin and gemfibrozil is possible only when the expected advantage significantly exceeds potential risk of such medicinal combination. Advantages of the combined use of a simvastatin of 10 mg a day and other fibrat (except a fenofibrat), niacin (more than 1 g/days) or cyclosporine have to be carefully weighed taking into account potential risk of such combinations.

There is a risk of development of a myopathy at purpose separately of a fenofibrat and a simvastatina therefore care at a concomitant use of this combination is necessary.

At reception of a simvastatin in the doses exceeding the 20th days it is necessary to avoid co-administration of Amiodaronum or verapamil, except for cases when the expected advantage surpasses potential risk of a myopathy.

Treatment simvastatiny can cause increase in activity of "hepatic" enzymes in blood serum. This increase is usually insignificant and clinically insignificant. After drug withdrawal levels of transaminases usually slowly decrease to initial level. Nevertheless, before an initiation of treatment and further it is necessary 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 1 time in half a year). In need of increase in a dose to 80 mg, control of function of a liver before increase in a dose, in 3 months after increase and then periodically (for example, 1 time in 6 months) within the first year of treatment is obligatory. At permanent increase in activity of ACT and/or ALT in blood serum by 3 times of rather upper bounds of norm, treatment simvastatiny it has to be stopped.

With care to appoint to the persons who are abusing alcohol, and/or having a liver disease in the anamnesis.

Drug is contraindicated at pregnancy. Increase in frequency of inborn defects at children of the women accepting симвастатин or other inhibitor of GMG-KOA-reduktazy is not proved. At reception by the pregnant woman of a simvastatin decrease at a fruit of levels of a mevalonat who is a predecessor of biosynthesis of cholesterol is possible. Cancellation of hypolipidemic means at pregnancy has no significant effect on results of the short-term risk connected with primary giperkho a lesterinemiya.

Simvastatin it is not necessary to apply at pregnant women, at the women planning pregnancy or at suspicion on pregnancy. 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.

It is not known whether drug in breast milk therefore therapy by the drug Vazilip® during breastfeeding is contraindicated is excreted.

About adverse influence of the drug Vazilip® on ability to drive the car and work with mechanisms it was not reported. Nevertheless, it is necessary to consider that at post-marketing use of a simvastatin isolated cases of dizziness are celebrated.

Side effects:

Classification of frequency of development of side effects (WHO):

very often> 1/10

often from> 1/100 to <1/10

infrequently from> 1/1000 to <1/100

seldom from> 1/10000 to <1/1000

very seldom from <1/10000, including separate messages.

From digestive tract, liver: seldom - a lock, abdominal pains, a meteorism, dyspepsia, nausea, vomiting, diarrhea, pancreatitis, hepatitis, jaundice, increase in activity of "hepatic" transaminases, an alkaline phosphatase, kreatinfosfokinaza (KFK).

From the central and peripheral nervous system and sense bodys: seldom - a headache, paresthesias, dizziness, peripheral neuropathy, an adynamy; sleeplessness, spasms, sight vagueness, disturbance of flavoring feelings.

From a musculoskeletal system: seldom - a myopathy, рабдомиолиз, a mialgiya, muscular spasms.

Allergic and immunopathological reactions: the developed hypersensitivity syndrome (a Quincke's disease, a volchanopodobny syndrome, a rheumatic polimialgiya, a dermatomyositis, a vasculitis, thrombocytopenia, an eosinophilia, increase in the blood sedimentation rate (BSR), arthritis, an arthralgia, a small tortoiseshell, a photosensitization, fever, "inflows" of blood to face skin, an asthma and the expressed weakness).

Dermatological reactions: seldom - skin rash, a skin itch, an alopecia.

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

Interaction with other medicines:

Pharmakodinamichesky interactions. Simultaneous use of a simvastatin from fibrata, niacin (more than 1 g/days) increases risk of development of a myopathy, including рабдомиолиз (at simultaneous use with fenofibraty - increase in risk of development of a myopathy in comparison with monotherapy by each drug separately is not proved). Simultaneous use with gemfibrozily can lead to increase in concentration of a simvastatin in blood serum.

Pharmacokinetic interactions. Inhibitors of the CYP3 A4 cytochrome (itrakonat, кетоконазол, erythromycin, кларитромицин, телитромицин, inhibitors of HIV proteases and нефазодон) participating in metabolic transformation of a simvastatin in a liver increase risk of development of a myopathy and rabdomioliz against the background of therapy simvastatiny. Simultaneous use with these drugs is contraindicated. With care it is necessary to appoint at the same time with less strong CYP3A4 inhibitors: cyclosporine, verapamil and diltiazem. The daily dose of a simvastatin at a concomitant use with cyclosporine should not exceed 10 mg. The daily dose of a simvastatin against the background of a concomitant use of Amiodaronum or verapamil should not exceed 20 mg, and 40 mg - against the background of a concomitant use of diltiazem if only the expected advantage obviously does not surpass potential risk of development of a myopathy and rabdomioliz.

Simvastatin in a dose of 20-40 mg/days at volunteers and patients with a hypercholesterolemia potentsiirut effects of coumarinic anticoagulants (for example, warfarin), in particular increase in a prothrombin time, the International Normalized Relation (MHO). Therefore at the patients accepting coumarinic anticoagulants, the prothrombin time and MHO needs to be defined before therapy simvastatiny, in an initial stage of treatment, at change of a dose of a simvastatin or drug withdrawal. At achievement of a stable indicator of a prothrombin time and MHO, further control needs to be carried out bucketed, recommended for the patients receiving therapy by anticoagulants. Therapy simvastatiny does not cause changes of a prothrombin time and risk of bleedings in the patients who are not accepting anticoagulants.

Grapefruit juice suppresses activity of CYP3A4. The concomitant use of a large number of grapefruit juice (more than 1 liter a day) and a simvastatina leads to significant increase in concentration in a blood plasma of simvastatinovy acid. Therefore, during therapy simvastatiny it is necessary to avoid the use of grapefruit juice.

Contraindications:

• Hypersensitivity to a simvastatin and other components of drug;
• liver diseases in an active phase or permanent increase in activity of "hepatic" transaminases of not clear etiology;
• concomitant use of inhibitors of P450 ZA4 cytochrome (CYP3A4) (for example, итраконазол, кетоконазол, inhibitors of HIV proteases, erythromycin, кларитромицин, телитромицин and нефазодон);
• pregnancy and period of a lactation;
• age up to 18 years (efficiency and safety of use are not studied).

With care: an alcohol abuse prior to therapy, liver diseases in the anamnesis, heavy disturbances of electrolytic balance, the expressed endocrine and metabolic disturbances, arterial hypotension, heavy acute infections (sepsis), a myopathy, uncontrollable epilepsy, extensive surgical interventions, an injury, deficit of lactase, a galactosemia or a sprue of glucose galactose (since drug contains lactose), a concomitant use with gemfibroziny, cyclosporine, niacin (more than 1 g/days), Amiodaronum, verapamil, diltiazem, fenofibraty, grapefruit juice.

Overdose:

There are overdoses of a simvastatin given about several cases the Maximum accepted dose makes 3,6 g.

Treatment: in case of overdose the symptomatic treatment is carried out; it is necessary to hold the general events: monitoring and maintenance of vital signs, prevention of further absorption of medicine (gastric lavage, reception of absorbent carbon or purgatives). Control of function of a liver and KFK is recommended. The specific antidote does not exist.

At development of a myopathy with rabdomiolizy (rare, but heavy side effect) it is necessary to stop immediately administration of drug, to enter to the patient diuretic and Natrii hydrocarbonas (intravenous infusion). Rabdomioliz can cause a hyperpotassemia which can be eliminated with intravenous administration 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:

List B. To store at a temperature not above 30 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, on 10 mg, 20 mg and 40 mg. On 7 tablets in the blister (blister strip packaging). On 2 or 4 blisters (blister strip packagings) together with the application instruction are placed in a pack from a cardboard.