Simvastatin - instructions for use, doses, side effects, contraindications

Excipients: potato starch 17.0 mg, lactose monohydrate 146.0 mg, ascorbic acid 5.0 mg, butyl hydroxytoluene 0.04 mg, citric acid 2.50 mg, pregelatinized starch 0.60 mg, povidone - 6.86 mg, magnesium stearate 2.0 mg.

Composition of the film shell: talc - 0.265 mg, titanium dioxide - 1.290 mg, hypromellose (hydroxypropylmethylcellulose) - 2,390 mg, macrogol 4000 - 1,047 mg, dye azorubin (acid red 2 C) 0.008 mg.

Description:

Round, biconvex tablets, covered with a film shell of pink color, allowed marbling of the surface. On a cross-section of almost white or white with a yellowish shade of color.

Pharmacotherapeutic group:lipid-lowering agent - HMG-CoA reductase inhibitor

ATX: & nbsp

C.10.A.A Inhibitors of HMG-CoA reductase

C.10.A.A.01 Simvastatin

Pharmacodynamics:

A hypolipidemic agent obtained synthetically from a fermentation product Aspergillus terreus, is an inactive lactone in the body undergoes hydrolysis with the formation of a hydroxy-acid derivative. The active metabolite inhibits 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), an enzyme that catalyzes the initial reaction of mevalonate formation from 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA). Since the conversion of HMG-CoA to mevalonate is an early stage in the synthesis of cholesterol, the use of simvastatin does not cause the accumulation of potentially toxic sterols in the body. HMG-CoA is easily metabolized to acetyl-CoA, which is involved in many synthesis processes in the body.

It causes a decrease in plasma concentrations of triglycerides (TG), low-density lipoproteins (LDL),lipoproteins of very low density (VLDL) and total cholesterol (in cases of heterozygous familial and non-family forms of hypercholesterolemia, with mixed hyperlipidemia, when elevated cholesterol concentration is a risk factor). Increases the concentration of high density lipoproteins (HDL) and reduces the ratio of LDL / HDL and total cholesterol / HDL.

The onset of the effect is 2 weeks after the start of therapy, the maximum therapeutic effect is achieved in 4-6 weeks. The effect persists with the continuation of treatment, with the cessation of therapy, the concentration of cholesterol gradually returns to the initial concentration observed before the start of treatment.

Pharmacokinetics:

Suction: after oral administration simvastatin absorbed from the gastrointestinal tract (GIT) - about 61-85% and enters the systemic circulation. The maximum therapeutic concentration in blood plasma is achieved after 1.3-2.4 hours and decreases by 90% after 12 hours. Simultaneous food intake does not affect the absorption of simvastatin.

Distribution: the binding to plasma proteins is about 98%. Metabolism: enters the body in an inactive form.Metabolized in the liver, has the effect of "primary transmission" through the liver. In the metabolism of the drug, isozymes participate CYP3A4, CYP3A5 and CYP3A7. T_1/2(half-life) of active metabolites is 1.9 hours. It hydrolyzes in tissues into its active form-beta-hydroxy acid and other inactive metabolites. The concentration of the active metabolite of simvastatin in the systemic circulation is 5% of the ingested dose.

Excretion: Simvastatin secreted in bile. It is excreted primarily through the intestine (about 60%) in the form of metabolites. The half-life of active metabolites is 1.9 hours. About 10-15% is excreted by the kidneys in an inactive form.

Indications:

Primary hypercholesterolemia Pa and Pb type according to Fredrickson classification with ineffectiveness of diet therapy with low cholesterol and other non-medicamentous measures (physical activity and weight loss in patients with an increased risk of coronary atherosclerosis).
Combined hypercholesterolemia and hypertriglyceridemia, not compensated by special diet and exercise.
Homozygous hereditary hypercholesterolemia (as an adjunct to hypolipidemic therapy).
Ischemic heart disease (secondary prophylaxis): the drug is indicated to patients in order to reduce the overall mortality; with the aim of reducing the risk of coronary mortality and the risk of developing myocardial infarction; with the aim of reducing the risk of stroke and transient cerebral circulatory disorders; to slow the progression of coronary atherosclerosis, reduce the risk of revascularization procedures, reduce the risk of the need for operations to restore the coronary and peripheral circulation.

Contraindications:

Hypersensitivity to the components of the drug and other inhibitors of HMG-CoA reductase in the anamnesis;
Hereditary lactose intolerance, lactase deficiency, glucosogalactose malabsorption;
Diseases of the liver in the active phase, persistent increase in the activity of "hepatic" transaminases of unclear etiology;
Simultaneous application with strong inhibitors of isoenzyme CYP3A4 (Itraconazole, ketoconazole, posaconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, klaritromi- tsinom, telithromycin, nefazodone, as well as voriconazole);
Concomitant treatment with gemfibrozil, cyclosporin or danazol;
Diseases of skeletal musculature (myopathy);
Pregnancy and women during breast-feeding; women of reproductive age who do not use reliable methods of contraception;
Age to 18 years (effectiveness and safety not established).

Carefully:

Assign patients with a high risk of developing diabetes, alcohol abusers, patients after organ transplantation, who are being treated with immunosuppressants (due to an increased risk of rhabdomyolysis and kidney failure), in conditions that can lead to the development of severe renal failure, as an arterial hypotension, acute infectious diseases of a heavy course, expressed metabolic and endocrine disturbances, disturbances of a water-electrolyte ball sa, surgery (including dental), or injury; patients with decreased or increased tone of skeletal muscles of unknown etiology; with epilepsy, uncontrolled convulsions.

Apply with caution at simultaneous administration with fibrates (except gemfibrozil), nicotinic acid in lipid-lowering doses (more than 1 g / day), amiodarone, verapamil, diltiazem, grapefruit juice, dronedarone, ranolazine, colchicine, fusidic acid because of the risk of myopathy and rhabdomyolysis; in patients with severe renal failure (CC <30 mL / min).

Pregnancy and lactation:

Simvastatin is contraindicated in pregnancy. Women of childbearing age who receive simvastatin, should avoid conception. The use of the drug is not recommended in women of childbearing age who do not use reliable methods of contraception.

If during pregnancy the pregnancy has occurred, it is necessary to cancel the drug intake Simvastatin, and a woman should be warned about possible dangers to the fetus due to the fact that HMG-CoA reductase inhibitors inhibit the synthesis of cholesterol, and cholesterol and other products of its synthesis play a significant role in the development of the fetus, including the synthesis of steroids and cell membranes.

The abolition of lipid-lowering drugs during pregnancy does not have a significant effect on the results of long-termtreatment of primary hypercholesterolemia.

Data on the isolation of simvastatin with breast milk are absent. If it is necessary to administer the drug Simvastatin women during feeding should be aware that many drugs are excreted in breast milk, and there is a threat of severe reactions, so breast-feeding while taking the drug is not recommended.

If it is necessary to administer the drug Simvastatin women during breastfeeding should stop breastfeeding.

Dosing and Administration:

Before the start of drug treatment, the patient should be prescribed a standard hypocholesterin diet, which should be observed throughout the course of treatment.

The recommended dose of the drug is from 5 to 80 mg per day.

The drug should be taken once a day in the evening. If necessary, the dose of the drug is increased at intervals of not less than 4 weeks, a maximum of 80 mg once a day.

Dose of 80 mg per day is recommended to be prescribed only for patients at high risk for cardiovascular complications, if the reception at lower doses would not achieve lipid targets, and the anticipated benefits of therapy outweighs the potential risk (see. Section "Special instructions" Miopa- ment / Rhabdomy lysis).

Patients with ischemic heart disease (CHD) or a high risk of developing coronary artery disease.

The standard initial dose of the drug for patients with a high risk of developing coronary artery disease in combination with or without hyperlipidemia (in the presence of diabetes, stroke or other cerebrovascular diseases in history, peripheral vascular disease), as well as for patients with ischemic heart disease is 40 mg 1 time per night in the evening. Drug therapy should be prescribed simultaneously with diet and exercise therapy.

Patients with hyperlipidemia who do not have the above risk factors.

The standard initial dose of simvastatin is 20 mg once a day in the evening. For patients who need a significant (more than 45%) reduction in the concentration of LDL-C, the initial dose may be 40 mg 1 time per day in the evening. Patients with mild or moderate hypercholesterolemia - recommended taking the drug at an initial dose of 10 mg once a day. Patients with homozygous familial hypercholesterolemia drug is recommended at a dose of 40 mg per day, taken once in the evening. A dose of 80 mg should be given only if the intended benefit of therapy exceeds the potential risk (see section Special instructions, Myopathy / Rhabdomyolysis).In such patients, the drug is used in combination with

other methods of lipid-lowering treatment (for example, LDL-apheresis) or without such treatment, if it is not available.

For patients taking lomitapid simultaneously with simvastatin, the daily dose of the latter should not exceed 40 mg.

Concomitant therapy

Simvastatin can be administered both in monotherapy and in combination with bile acid secretants.

Patients receiving simvastatin concurrent with fibrates other than gemfibrozil (see the section "Contraindications") or fenofibrate, the maximum recommended dose of the drug is 10 mg per day. For patients receiving amiodarone, verapamil, diltiazem or amlodipine Simvastatin simultaneously, the daily dose of the latter should not exceed 20 mg.

Renal insufficiency

Because the simvastatin is excreted by the kidneys in small amounts, there is no need to change the doses in patients with moderate renal dysfunction. In patients with severe renal failure (CK <30 ml / min), the expediency of prescribing the drug in doses exceeding 10 mg per day should be carefully weighed.If such dosages are considered necessary, they should be administered with caution.

Side effects:

From the digestive tract: abdominal pain, constipation, flatulence, nausea, diarrhea, pancreatitis, vomiting, hepatitis.

From the central and peripheral nervous system: asthenic syndrome, loss or loss of memory, depression, sleep disturbance, including insomnia and nightmarish dreams, headache, dizziness, muscle cramps, paresthesia, peripheral neuropathy, blurred vision, impaired taste.

Allergic and immunopathological reactions: angioedema,

Rheumatic polymyalgia, vasculitis, thrombocytopenia, increased ESR,

fever, arthritis, urticaria, dyspnea, lupus-like syndrome, eosinophilia.

From the skin and subcutaneous fat: skin photosensitivity, skin hyperemia, "tides" of blood to the skin of the face, rash, itching, alopecia, dermatomyositis.

From the side of the musculoskeletal system and connective tissue: Myopathy, myalgia, muscle cramps, weakness; rhabdomyolysis; cases of development of immuno-mediated necrotizing myopathy.

Laboratory and instrumental data: increased activity of "liver" transaminases, alkaline phosphatase and creatine phosphokinase (CK), hyperglycemia, increased concentration of glycosylated hemoglobin, thrombocytopenia.

Other: anemia, palpitations, acute renal failure (due to rhabdomyolysis), sexual dysfunction (decreased potency), gynecomastia, single cases of interstitial lung disease (especially with prolonged use).

Overdose:

In none of the known few cases of overdose (the maximum dose of 450 mg) specific symptoms were identified.

Treatment: rinse the stomach, take Activated carbon. Symptomatic therapy. It is necessary to monitor the liver and kidney function, the activity of CKK in the blood serum.

With the development of myopathy with rhabdomyolysis and acute renal failure (a rare but severe side effect), stop taking the medication immediately and administer the patient diuretic and sodium hydrogen carbonate (intravenous infusion). If necessary, hemodialysis is indicated.

Rhabdomyolysis can cause hyperkalemia,which can be eliminated by intravenous administration of calcium chloride or calcium gluconate, infusion of dextrose with insulin, the use of potassium ion exchange resins.

Interaction:

Contraindicated combination of drugs

Contraindicated concomitant therapy with the following drugs: Powerful inhibitors of isoenzyme CYP3A4: simvastatin is metabolized by isoenzyme CYP3A4, but does not inhibit the activity of this isoenzyme, this suggests that the use of simvastatin does not affect the concentration in the blood plasma of drugs metabolizing under the action of the isoenzyme CYP3A4. Powerful inhibitors of isoenzyme CYP3A4 increase the risk of myopathy by decreasing the rate of excretion of simvastatin. Simultaneous use of potent inhibitors of isoenzyme CYP3A4 (eg itraconazole, ketoconazolam, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone) and simvastatin is contraindicated. (see the sections "Contraindications", "Special instructions", Myopathy / Rabdomio l of).

Concomitant treatment with gemfibrozil, cyclosporin or danazol is not recommended (see p.section "Contraindications", "Special instructions", Myopathy / Rhabdomyolysis).

Interaction with other drugs

Amiodarone and verapamil: The risk of myopathy increases with the joint administration of amiodarone or verapamil with high doses of simvastatin. With the joint administration of dronedarone or ranolazine with simvastatin increases the risk of myopathy and rhabdomyolysis.

Diltiazem: The risk of myopathy is slightly increased in patients receiving diltiazem simultaneously with simvastatinom in a dose of 80 mg.

With the simultaneous use of simvastatin with fusidic acid, the risk of myopathy increases.

With the simultaneous use of colchicine and simvastatin in patients with impaired renal function, cases of myopathy and rhabdomyolysis are described (monitoring of patients' condition is necessary).

Simvastatin potentiates the action oral anticoagulants (for example,

measures, fenprokumone, warfarin) and increases the risk of bleeding, which requires the need to monitor the coagulability of the blood before treatment, and often enough in the initial period of therapy.Once a stable level of prothrombin time or an international normalized ratio (INR) is reached, its further control should be performed at intervals recommended for patients receiving anticoagulant therapy. When changing the dose or stopping the intake of simvastatin, it should also be monitored prothrombin time or INR in the above scheme.

Therapy with simvastatin does not cause changes in prothrombin time and the risk of bleeding in patients who do not take anticoagulants. Increases concentration digoxin in the blood plasma.

Kolestyramine and colestipol reduce the bioavailability (the use of simvastatin is possible 4 hours after the administration of these drugs, with an additive effect noted).

Grapefruit juice contains one or more components that inhibit the isoenzyme CYP3A4 and can increase the concentration in the blood plasma of metabolites isoenzyme CYP3A4. The increase in the activity of HMG-CoA reductase inhibitors after consuming 250 ml of juice per day is minimal and has no clinical significance.However, consumption of a large amount of juice (more than 1 liter per day) with the use of simvastatin significantly increases the level of inhibitory activity against HMG-CoA reductase in blood plasma. In this regard, against the background of taking simvastatin should be avoided the use of grapefruit juice in large quantities.

Special instructions:

Myopathy / Rhabdomyolysis

Simvastatin, like other inhibitors of GM-CoA reductase, can cause Myopathy, which manifests itself in the form of muscle pain, soreness, or weakness and is accompanied by an increase in the activity of CKK (more than 10 times higher than the upper limit of the norm (VGN)). Myopathy can manifest itself in the form of rhabdomyolysis, sometimes accompanied by secondary acute renal failure due to myoglobinuria. In rare cases, a lethal outcome was observed. The risk of developing myopathy is increased by increasing the concentration in the blood plasma of substances that have an inhibitory effect on HMG-CoA reductase. Risk factors for myopathy development include elderly age (> 65 years), female gender, uncontrolled hypothyroidism and renal dysfunction.

As with other HMG-CoA reductase inhibitors, the risk of myopathy / rhabdomyolysis depends on the dose. In clinical studies (the median duration of follow-up was 4 years), the incidence of myopathy with doses of 20, 40 and 80 mg per day was 0.03%, 0.08%, and 0.61%, respectively. In these studies, patients were closely monitored, and a number of drugs that could interact with simvastatin were not used.

In a clinical study in which patients with a history of myocardial infarction took simvastatin at a dose of 80 mg per day (mean follow-up 6,7 years), the incidence of myopathy was approximately 1.0%, and in patients taking the drug at a dose of 20 mg per day, 0.02%. Approximately half the cases of myopathy were reported during the first year of treatment. The frequency of myopathy during each next year of treatment was approximately 0.1%.

In patients receiving simvastatin in a dose of 80 mg per day, the risk of developing myopathy is higher than when using other statins that cause a comparable decrease in LDL cholesterol. Consequently, simvastatin in a dose of 80 mg per day should be prescribed only patients with a high risk of cardiovascular complications in whom drug therapy at lower doses did not achieve a therapeutic effect, and the perceived benefit of treatment exceeds the possible risk. If to the patient, acceptmaturing simvastatin in a dose of 80 mg, treatment with another drug that can interact with simvastatin is required, then it is necessary to reduce the dose of simvastatin or to prescribe another statin that has less potential for drug interaction (see Contraindications and Dosage and Administration).

All patients who start therapy with the drug Simvastatin, as well as patients who need to increase the dose should be warned about the possibility of myopathy and are informed of the need to immediately seek medical attention in the event of any unexplained pain, muscle soreness or muscle weakness. Drug therapy Simvastatin should be immediately discontinued if myopathy is diagnosed or at least assumed. The presence of the above symptoms and / or more than 10-fold increase in CKK activity in comparison with IGN indicate the presence of myopathy.In most cases, after an immediate discontinuation of simvastatin, the symptoms of myopathy are resolved, and the activity of CK decreases. In patients starting to take simvastatin or switching to increasing the dose of the drug, it is advisable to periodically determine the activity of CKK, but there is no guarantee that such monitoring can prevent the development of myopathy.

Many of the patients who underwent rhabdomyolysis during simvastatin therapy had a complicated history, including renal dysfunction, usually as a result of diabetes mellitus. Such patients require more careful observation.

Therapy with simvastatin should be temporarily discontinued in patients a few days before performing large surgical interventions, as well as in the postoperative period.

The risk of developing myopathy / rhabdomyolysis increases with the simultaneous use of simvastatin with the following drugs:

Contraindications

Powerful inhibitors of isoenzyme CYP3A4: concomitant therapy with potent inhibitors of isoenzyme CYP3A4 in therapeutic doses (for example, itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, HIV protease inhibitors, boceprevirov, telaprevir or nefazodone) is contraindicated.If treatment with itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin or telithromycin can not be avoided, the therapy with simvastatin should be interrupted for the period of their use (see the section "Contraindications" and "Interaction with other medicinal products"),
Gemfibrozil, ciclosporin or danazol: simultaneous use of these drugs with simvastatin is contraindicated (see the section "Contraindications and interaction with other medicinal products").

Other drugs

Other fibrates: in patients taking fibrates other than gemfibrozil (see the section "Contraindications") or fenofibrate, the dose of simvastatin should not exceed 10 mg per day. With the simultaneous use of simvastatin and fenofibrate, the risk of developing myopathy does not exceed the amount of risks in treatment with each drug individually. Assign fenofibrate In combination with simvastatin should be cautious, since both drugs can cause myopathy. The adherence of fibrates to simvastatin usually leads to a slight additional decrease in the concentration of LDL cholesterol, but allows a more pronounced decrease in TG concentration and an increase in the concentration of HDL cholesterol.In small short clinical trials in which both drugs were used under close observation, combined therapy with fibrates with simvastatin was not accompanied by the development of myopathy (see section "Interaction with other drugs").

Amiodaroy: in patients taking amiodarone, the dose of simvastatin should not exceed 20 mg per day (see the section "Interaction with other medicinal products").

Blocks of "slow" calcium channels

Verapamil or diltiazem: in patients taking verapamil or diltiazem, the dose of simvastatin should not exceed 20 mg per day (see the section "Interaction with other medicinal products").
Amlodipine: in patients taking amlodipine, the dose of simvastatin should not exceed 40 mg per day (see the section "Interaction with other medicinal products").

Moderate inhibitors of isoenzyme CYP3A4: while simultaneous use of drugs with moderate inhibitory activity against isoenzyme CYP3A4, and simvastatin, especially at higher doses, may increase the risk of developing myopathy.

Fusidic acid: in patients taking both fusidic acid and simvastatin, may increase the risk of myopathy (see the section "Interaction with other drugs"). When fusidic acid and simvastatin are used concomitantly, patients should be carefully monitored and there may be a break in the treatment with simvastatin.

Nicotinic acid (> 1 g / day): with simultaneous use of simvastatin and nicotinic acid in lipid-lowering doses (> 1 g / day), cases of development of myopathy / rhabdomyolysis have been described. In a continuing double-blind, randomized clinical trial in China, the UK and Scandinavia, an interim safety analysis performed by an independent committee showed that the incidence of myopathy in approximately 4,700 patients (UK / Scandinavia), receivedof the simvastatin 40 mg or ezetimibe / simvastatin 10/40 mg in combination with sustained release laropiprant / nicotinic acid at a dose of 40 mg / 2 g was comparable to the overall incidence of myopathy in all clinical trials of simvastatin 40 mg (0.08%).However, in about 3900 Chinese patients in the same group, the incidence of myopathy was higher than expected (approximately 0.9%). In the control group (placebo + simvastatin 40 mg or ezetimibe / simvastatin 10/40 mg), the risk of myopathy in 8600 patients of Chinese, British and Scandinavian nationalities was not increased. Given the higher incidence of myopathy in Chinese patients, caution should be exercised when taking simvastatin (especially at doses> 40 mg) in combination with nicotinic acid or preparations containing nicotine a new acid, in lipid-lowering doses (> 1 g / day) in representatives of a given nationality. Since the risk of developing myopathy depends on the dose, therefore, it is not advisable for patients of Chinese nationality to prescribe simvastatin in a dose of 80 mg in combination with nicotinic acid or preparations containing nicotinic acid, in lipid-lowering doses (> 1 g / day). There are no data on the increased risk of myopathy in combination with other representatives of the Mongoloid race (see "Interaction with Other Drugs").

Effects on the liver

In some adult patients who took simvastatin, there was a steady increase in the level of activity of "hepatic" enzymes (more than 3 times higher than UGN). With the termination or interruption of the prescription of the drug, the activity of "hepatic" transaminases usually returns gradually to the baseline level. Increased activity of "liver" transaminases was not associated with jaundice or other clinical symptoms. No hypersensitivity reactions were identified. Some of the above patients had abnormalities in the results of functional hepatic samples prior to commencement of treatment with simvastatin and / or abused alcohol.

Before beginning treatment, and then in accordance with clinical indications, all patients are recommended to conduct a study of liver function. Patients who are scheduled to increase the dose of simvastatin up to 80 mg per day should perform additional liver function tests before switching to the specified dosage, then 3 months after the start of its use and then regularly repeat (for example, every six months) throughout first year of treatment.Particular attention should be given to patients with increased serum transaminase activity. These patients need to repeat the test in the near future and subsequently conduct it regularly until the activity of serum transaminases is normalized. In cases when the activity of "hepatic" transaminases increases, especially with a stable excess of 3 times VGN, the drug should be discarded. The cause of increased activity of alanine aminotransferase (ALT) may be muscle damage, so the increase in activity of ALT and CK can indicate the development of myopathy (see section "Special instructions, Myopathy / Rhabdomyolysis ").

There were rare post-registration reports of fatal and non-fatal cases of liver failure in patients with_gincluding statins, including simvastatin. If severe liver disease with clinical symptoms and / or hyperbilirubinemia or jaundice develops with simvastatin treatment, therapy should be discontinued immediately. If another cause of the development of this pathology has not been identified, reassignment of simvastatin is contraindicated.

In patients who abuse alcohol and / or patients with impaired liver function, the drug should be used with extreme caution. Active liver disease or unexplained increase in aminotransferase activity are contraindications to the appointment of simvastatin.

During the treatment with simvastatin, as in the case of treatment with other lipid-lowering drugs, a moderate (less than 3 times higher than UGN) increase in the activity of serum transaminases was observed. These changes appeared soon after the start of treatment, often were transient, were not accompanied by any symptoms and did not require interruption of treatment.

Ophthalmological examination

The data of modern long-term clinical studies do not contain information on the adverse effects of simvastatin on the lens of the human eye.

Use in children and adolescents aged 10-17 years

The safety and efficacy of simvastatin in children and adolescents aged 10-17 years with heterozygous familial hypercholesterolemia were evaluated in controlled clinical trials involving 10-17 year olds and 10-17 year olds not less than 1 year after menarche.In patients of childhood, who took simvastatin, the side effect profile was similar to that of patients taking placebo. The use of simvastatin at a dose> 40 mg per day has not been studied in patients of childhood and adolescence. In this study, there was no significant effect of taking simvastatin on the growth and sexual maturation of young men and girls, or any effect on the length of the menstrual cycle in girls. Girls should be consulted about proper methods of contraception during treatment with simvastatin (see "Contraindications", "Pregnancy and Breastfeeding"). The use of simvastatin has not been studied in children younger than 10 years and in girls 10-17 years before menarche.

Use in elderly patients

In patients over the age of 65 years, the effectiveness of simvastatin, evaluatethe level of decrease in the concentration of OXC and LDL cholesterol is the same as for in the population as a whole, a significant increase in the frequency of clinical orboratory side effects were not observed. However, in a clinical study of the use of simvastatin 80 mg / day in patients older than 65 years, there was an increased risk of developingmyopathy compared with patients younger than 65 years.

Effect on the ability to drive transp. cf. and fur:

The adverse effect of simvastatin on the ability to drive vehicles and work with mechanisms has not been reported. Nevertheless, it should be taken into account that dizziness and other side effects may occur when using the drug, which may affect these abilities, but caution should be exercised.

Form release / dosage:

Tablets, film-coated, 20 mg.

For 10 or 14 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

According to 1, 2, 3, 4 or 5 contour cell packs of 10 tablets or 2 contour packs of 14 tablets, together with the instructions for use are placed in a pack of cardboard.

Packaging:

For 10 or 14 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

According to 1, 2, 3, 4 or 5 contour cell packs of 10 tablets or 2 contour packs of 14 tablets, together with the instructions for use are placed in a pack of cardboard.

Storage conditions:

In a place protected from moisture and light, at a temperature not exceeding 30 ° С. Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N003369 / 01

Date of registration:21.05.2009

The owner of the registration certificate:AVVA RUS, OJSC AVVA RUS, OJSC Russia

Manufacturer: & nbsp

AVVA RUS, OJSC Russia

Representation: & nbspAVVA ENG JSC AVVA ENG JSC Russia

Information update date: & nbsp31.07.2015

Illustrated instructions

Instructions

Simvastatin (Simvastatin)