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

Excipients: lactose monohydrate - 69.23 mg, corn starch 7.00 mg. cellulose microcrystalline - 5.00 mg, ascorbic acid - 2.50 mg, gynrolosis (hydroxypropyl cellulose) -2.0 mg, croscarmellose sodium - 2.00 mg, citric acid monohydrate - 1.25 mg. butyl hydroxy anisole - 0.02 mg, calcium stearate - 1.00 mg;

film sheath: [hypromellose - 2.0000 mg, gynrolase (hydroxypropylcellulose) 0.7760 mg, talc 0.7704 mg, titanium dioxide 0.0440 mg, iron oxide black (iron oxide) 0.1616 mg,iron oxide red (iron oxide) - 0.1560 mg, iron oxide yellow (iron oxide) - 0.0920 mg] or [dry mixture for film coating. containing hypromellose (50%), gnprolose (hydroxypropyl cellulose) (19.4%). talc (19.26%). titanium dioxide (1.1%), iron oxide black (iron oxide) (4.04%), iron oxide red (iron oxide) (3.9%), iron oxide yellow (iron oxide) (2.3%)] - 4, 0000 mg.

Dosage of 20 mg

active substance: simvasmatin - 20.00 mg;

auxiliary substances: lactose monohydrate - 138.46 mg. corn starch - 14.00 mg, microcrystalline cellulose - 10.00 mg, ascorbic acid - 5.00 mg, gynrolase (hydroxypropyl cellulose) - 4.00 mg, croscarmellose sodium - 4.00 mg, citric acid monohydrate - 2.50 mg, butyl hydroxy anisole - 0.04 mg, calcium stearate - 2.00 mg;

film shell: [hypromellose - 4.0000 mg, ginrolose (hydroxypropylcellulose) 1.5520 mg, talc 1.5408 mg, titanium dioxide 0.0880 mg, iron oxide black (iron oxide) 0.33232 mg, iron oxide red (iron oxide) 0.3120 mg , iron oxide yellow (iron oxide) 0.1840 mg] or [dry film-coating mixture containing hypromellose (50%), giprolose (hydroxypropyl cellulose) (19.4%), talc (19.26%), titanium dioxide (1.1%), iron oxide black (iron oxide) (4.04%), iron oxide red (iron oxide) (3.9%),iron oxide yellow (iron oxide) (2.3%)] - 8.0000 mg.

Description:Round biconvex tablets, covered with a film coating of brown color. On the cross section, the nucleus is white or almost white in color.

ATX: & nbsp

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

C.10.A.A.01 Simvastatin

Pharmacodynamics:The hyiolipidemic agent obtained synthetically from the fermentation product of Aspergillus terreus is an inactive lactone, in the body it 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 HMG-CoA. Since the conversion of HMG-CoA to mevalonate is an early stage in the synthesis of cholesterol (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), very low density lipoproteins (VLDL) and total cholesterol (OCS) (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 lipoprotein (HDL) and reduces the ratio of LDL / HDL and OXC / HDL in blood plasma.

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

Pharmacokinetics:

Absorption of simvastatin is high (about 85%), taking a meal (against the background of a standard hypocholesterol diet) immediately after taking the drug, nc influences the pharmacokinetic profile of simvastatin. After oral administration, the maximum concentration in the blood plasma is reached after approximately 1.3-2.4 hours and decreases by 90% after 12 hours. The connection with plasma proteins is about 95%.

Metabolized in the liver, has the effect of "primary passage" through the liver (hydrolyses to form an active derivative: beta-hydroxy acid, other active as well as inactive metabolites are found).The half-life of active metabolites is 1.9 hours.

It is excreted primarily through the intestine (60%) in the form of metabolites. About 10-15% is excreted by the kidneys in an inactive form

Indications:Hypercholesterenia (for patients older than 18 years)

as an addition to the diet, when the application of only diet and other non-pharmacological treatments is not enough for:
decrease in increased concentration of OXC, LDL cholesterol. TG, apolipoprotein B (apo B);
increased HDL cholesterol in patients with primary hypercholesterolemia, including heterozygous familial hypercholesterolemia (Fredrickson type hyperlipidemia), or mixed hypercholesterolemia (type II hyperlipidemia according to Fredrickson classification);
reducing the ratio of LDL / HDL and LDL / LDL cholesterol;
hypertriglyceridemia (type IV hyperlipidemia according to Fredrickson classification);
supplement to the diet and other ways of treating patients with homozygous familial hypercholesterolemia to reduce elevated concentrations of OXC, LDL cholesterol and apo B;
primary dysbetalnoproteinemia (type III hyperlipidemia according to Fredrickson classification).

Patients with ischemic heart disease (CHD) or a high risk of cardiovascular complications (for patients older than 18 years):

in patients with a high risk of cardiovascular complications (with or without hyperlipidemia), for example, patients with IHD or a predisposition to IHD, with diabetes mellitus, with stroke or other cerebrovascular diseases in the history, patients with peripheral vascular disease, the drug is indicated for the purpose of:

reducing the risk of overall mortality by reducing mortality due to coronary artery disease;

- reducing the risk of serious vascular and coronary events:

non-fatal myocardial infarction;
coronary death;
stroke;
revascularization procedures;

reduction in the risk of need for surgical interventions to restore coronary blood flow (such as coronary artery bypass grafting and percutaneous transluminal coronary angioplasty);
reducing the risk of the need for surgical interventions to restore peripheral blood flow and other types of non-coronary revascularization;
reduce the risk of hospitalization in connection with attacks of angina pectoris.

Application v children and adolescents 10-17 years old with heterozygous familial hypercholesterolemia:

drug administration Simvastatin Simultaneously with the diet it is shown to reduce the elevated concentration of OXC, LDL cholesterol, TG, alo B in young men of 10-17 years and in girls 10-17 years not less than 1 year after menarche (the first menstrual bleeding) with heterozygous familial hypercholesterolemia.

Contraindications:

increased sensitivity to simvastatin or to other components of the drug, as well as to other drugs of the statin series (inhibitors of GMC-CoA reductase) in the anamnesis;
liver disease in the active phase, persistent increase in the activity of liver enzymes of unknown etiology;
diseases of skeletal muscles (myopathy);
lactose intolerance; deficiency of lactase; glucose-galactosia malabsorption;
age to 18 years (except for children and adolescents 10-17 years with heterozygous familial hypercholesterolemia);
simultaneous application with strong inhibitors of the isoenzyme CYP3A4 (itraconazole, ketoconazole, posaconazole, HIV protease inhibitors, boceprevirov, telaprevir, erythromycin, clarithromycin, gelmitromycin, nsphazodone, voriconazole and preparations containing the co-bicystate);
concomitant treatment with gemfibrozil, cyclosporin, or danazol;
use in women planning pregnancy and women of reproductive age who do not use reliable methods of contraception;
- Pregnancy;
the period of breastfeeding.

Carefully:

Simvastatin is prescribed with caution in patients who abuse alcohol, transplant patients undergoing immunosuppressive therapy (due to an increased risk of rhabdomyolysis and renal failure); under conditions that can lead to severe renal insufficiency, such as hypotension, acute infectious disease severe expressed metabolic and endo- Crean violations, violations

water-electrolyte balance, surgical interventions (including dental), or trauma; patients with decreased or increased tone of skeletal muscles of unknown etiology; patients with epilepsy; patients with severe renal insufficiency (creatinine clearance (CK) less than 30 ml / min); patients with hereditary muscle diseases; patients with a high risk of diabetes; elderly patients (over 65 years of age); with simultaneousapplication with nicotinic acid in lipid-lowering doses (more than 1 r / day), amiodarone, amlodipine, veranamil, diltiazem, colchicine, fusic acid, ranolazine, dronedarone (increased risk of myopathy and rhabdomyolysis), grapefruit juice.

Pregnancy and lactation:

Simvastatin is contraindicated in pregnancy. Since safety for pregnant women is not proven and there is no evidence that treatment with the drug during pregnancy brings obvious benefits, taking the drug should stop immediately when diagnosing pregnancy. There are several reports of the development of anomalies in newborns. whose mothers simvastatin.

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

In connection with the fact that inhibitors of HMG-CoA reductase inhibit the synthesis of cholesterol, and cholesterol and other products of its synthesis play an important role in the development of the fetus, including the synthesis of steroids and cell membranes, simvastatin may have an adverse effect on the fetus when prescribing it to pregnant women.Women of childbearing age who receive simvastatin, must follow reliable contraceptive measures. A drug Simvastatin should be prescribed to women of childbearing age only in those cases when the probability of pregnancy is very small. Treatment with the drug should be suspended for the entire duration of pregnancy or until pregnancy is diagnosed, and the woman herself is warned about the possible danger to the fetus.

Data on the isolation of simvastatin and its metabolites with breast milk are absent. If it is necessary to prescribe Simvastatin during breastfeeding, it should be borne in mind that many drugs are excreted in breast milk and there is a threat of severe reactions, so breast-feeding during drug intake should be discontinued.

Dosing and Administration:

Before starting treatment with Simvastatin, the patient should be prescribed a standard gyno-cholesterol diet, which should be observed throughout the course of treatment.

A drug Simvastatin should be taken orally 1 time per day in the evening, with plenty of water. Recommended daily doses range from 5 to 80 mg.To ensure the dosage regimen of the drug at a dose of 5 mg, it is recommended to use simvastatin preparations in another dosage form: film-coated tablets, 5 mg or film-coated tablets, 10 mg with a risk. Dose titration should be performed at intervals of 4 weeks. A dose of 80 mg per day is recommended to be prescribed only to patients with a high risk of cardiovascular complications, if treatment with the drug at lower doses does not allow achieving target lipid levels, and the estimated benefit from therapy exceeds the possible risk.

In patients with familial homozygous hypercholesterolemia, the recommended daily dose of the drug Simvastatin is 40 mg per day, once in the evening. A dose of 80 mg per day is recommended to be used only if the presumed benefit of therapy exceeds the possible risk. In such patients, the drug Simvastatin are used in combination with other methods of lipid-lowering treatment (for example, plasmapheresis of LDL) or without such treatment, if it is not available.

In the treatment of patients with IHD or a high risk of cardiovascular complications, the standard initial dose of the drugSimvastatin for patients at 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 per day.

In patients with hyperlipidemia who do not have the above risk factors, the standard initial dose is 20 mg once a day in the evening. In patients with an LDL concentration in the blood plasma that exceeds normal values by 45%, the initial dose may be 40 mg / day. Patients with mild to moderate hypercholesterolemia drug therapy Simvastatin you can start with a dose of 10 mg / day.

For patients who simultaneously take fibrates, in addition to fenofibrate, the maximum daily dose of simvastatin is 10 mg. Concomitant use with gemfibrozilom contraindicated.

In patients who simultaneously take verapamil, diltiazem and dronedaron, the maximum daily dose is 10 mg. For patients who simultaneously take amiodarone, amlodipine, ranolazine, the maximum daily dose of simvastatin is 20 mg.

Patients with chronic renal insufficiency: in patients with impaired renal function of mild and moderate severity (QC more than 30 ml / min) dose adjustment is not required. In patients with severe renal dysfunction (CK less than 30 ml / min) or taking simultaneously fibrates and nicotinic acid in lipid-lowering doses (more than 1 g / day), the initial dose is 5 mg, and the maximum allowable daily dose is 10 mg.

In elderly patients (over 65 years), dose adjustment is not required.

Use in children and adolescents K) -17 years with heterozygous familial hypercholesterolemia '. the recommended initial dose is 10 mg per day in the evening. The recommended dosage regimen is 10-40 mg per day, the maximum recommended dose of the drug is 40 mg per day. Selection of doses is made individually according to the purposes of therapy.

In case of missing the current dose, the drug should be taken as soon as possible. If it is time to take the next dose, the dose should not be doubled.

Side effects:

Classification of the incidence of side effects according to the recommendations of the World Health Organization (WHO): very often> 1/10; often from> 1/100 to <1/10;

infrequently from> 1/1000 to <1/100; rarely from> 1/10000 to <1/1000;

very rarely <1/10000, including individual messages;

the frequency is unknown - it is not possible to establish the frequency of occurrence from the available data. Digestive system: rarely - abdominal pain, constipation, flatulence, nausea, diarrhea, pancreatitis, vomiting, hepatitis / jaundice, increased activity of "liver" transaminases, gamma-glutamyltranspeptidase, alkaline phosphatase;

very rarely - fatal and nonfatal liver failure, increased activity of creatine phosphokinase (CK). Nervous system and sensory organs: rarely - headache, dizziness, peripheral neuropathy, paresthesia, muscle cramps;

very rarely - sleep disturbances, including insomnia and "nightmarish" dreams; blurred vision; the frequency is unknown - depression, a violation of taste sensations, asthenic syndrome. Allergic and immunopathological reactions: rarely angioedema, rheumatic polymyalgia, vasculitis, thrombocytopenia, increased erythrocyte sedimentation rate (ESR), skin hyperemia, hot flashes, lupus-like syndrome, arthritis, fever, urticaria, photosensitivity,shortness of breath, eosinophilia; frequency unknown - toxic epidermal necrolysis, including Sti veins Sa-D-jo neon syndrome. Dermatological reactions: rarely - skin rash, itching, alopecia, dermatomyositis. On the part of the musculoskeletal system: rarely - miapgiya, muscle cramps, weakness, rhabdomyolysis, polymyositis, arthralgia, myo Patiala; the frequency is unknown - tendonopathy, possibly with a rupture of tendons. From the respiratory system: unknown frequency - interstitial lung disease (especially with prolonged use), bronchitis, sinusitis. Other: rarely - anemia, general weakness; frequency is unknown - palpitations, acute renal failure (due to rhabdomyolysis), urinary tract infections, reduced potency, sexual dysfunction, gynaecomastia. With the use of statins, including simva- statin reported with immuno onoeredovannoy necrotizing miopa- TII, increasing concentrations of hemoglobin and glycosylated Rowan concentration in serum fasting glucose, diabetes. The incidence of diabetes mellitus is dependent on the presence or absence of risk factors (fasting blood glucose concentration more than 5.6 mmol / L, body mass index greater than 30 kg / m2, the increased concentration of TG in the blood plasma,arterial hypertension in anamnesis).

Also reported was the loss or decline of memory associated with taking statins. Children and adolescents (10-17 years)

According to a study of one year duration in children and adolescents (boys in the Tenner stage II and above and girls, but at least one year after the first menstruation) at the age of 10-17 with heterozygous familial hypercholesterolemia (n = 175), the safety profile in group that applies simvastatin, was similar to the profile of the placebo group. Long-term effects on physical, intellectual and sexual development are not known. At the moment, there is insufficient safety data.

Interaction:

Strong inhibitors of the CYP3A4 isoenzyme increase the risk of myopathy and rhabdomyolysis by increasing the inhibitory activity of GMC-CoA reductase in blood plasma during treatment with simvastatin. Simultaneous use of strong inhibitors of the isoenzyme CYP3A4 (for example, ketoconazole, itraconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telstrevir, nefazodone, drugs containing the co-cystatite) and simvastatin is contraindicated .The concomitant use of cyclosporine or danazol with simvastatin is contraindicated (see section "Contraindications"), as the risk of myopathy and / rhabdomy and olosis increases.

When joint therapy with the drug Simvastatin with the drugs listed below, in connection with the risk of myopathy, patients should be carefully monitored.

Fibrates: the risk of developing myopathy, including rhabdomyolysis, increases with the joint appointment of simvastatin with fibrates. There is no evidence of an increased risk of myopathy with simultaneous use of simvastatin and fenofibrate. Controlled studies on interactions with other fibrates have not been conducted. Simultaneous use with gemfibrozil leads to an increase in the plasma concentration of simvastatin, therefore the simultaneous use of simvastatin with gembibrosil is contraindicated (see section "Contraindications").

Dronedarone is a moderate inhibitor of the CYP3A4 isoenzyme and a potent inhibitor of P-glycoprotein transport, so simultaneous use with simvastatin may increase the systemic exposure of simvastatin and hydroxy acidssimvastatin, which are substrates of the isoenzyme CYP3A4 and P-glycoprotein, and lead to an increased risk of myopathy. Against the background of dronedarone, a reduction in the dose of simvastatin may be required.

Inhibitors of transport protein OATP1B1

The hydroxy acid of simvastatin is a substrate of the transport protein OATP1B1, simultaneous application of transport protein inhibitors OATP1B1 and simvastatin may lead to an increase in the plasma concentration of the hydroxy acid of simvastatin and an increased risk of myopathy.

Nicotinic acid in lipid-lowering doses (more than 1 g / day) ', cases of development of myopathy / rhabdomyolysis with simultaneous application of simvastatin and nicotinic acid in lipid-lowering doses (more than 1 g / day) have been observed.

Fusidic acid: the risk of developing myopathy increases with simultaneous use of fusidic acid with statins, including simvastatin. If it is not possible, for any reason, to avoid the simultaneous use of simvastatin with fusidic acid, it is recommended to consider the possibility of postponing treatment with simvastatin.

Immunosuppressants increase the risk of myopathy with simultaneous use with simvastatin.

Danazol: the risk of developing myopathy / rhabdomyolysis increases with simultaneous use of danazol, especially with high doses of simvastatin (see section "Contraindications").

Amiodarop: the risk of developing myopathy increases with the simultaneous administration of amiodarone with high doses of simvastatin. In clinical trials, the development of myopathy was detected in 6% of patients who used simvastatin in a dose of 80 mg together with amiodarone. The dose of simvastatin should not exceed 20 mg per day in patients using the drug concomitantly with amiodarone if the clinical benefit exceeds the risk of developing myopathy and rhabdomyolysis.

Blockers of "slow" calcium channels, which increase the risk of myopathy / rhabdomyolysis with simultaneous use with simvastatin. Verapamil: the risk of myopathy and rhabdomyolysis increases with the use of verapamil with simvastatin in doses greater than 40 mg. The dose of simvastatin should not exceed 10 mg per day in patients using the drug concomitantly with verapamil if the clinical benefit exceeds the risk of developing myopathy and rhabdomyolysis. Amlodipine: Patients who use amlodipine concomitantly with simvastatin at a dose of 80 mg fall into a group at increased risk of developing myopathy.With the simultaneous use of simvastatin in a dose of 40 mg with amlodipine, the risk of developing myopathy did not increase. When simvastatin is used with amlodipine, the dose of simvastatin should not exceed 20 mg per day if the clinical benefit exceeds the risk of myopathy / rhabdomyolysis. Diltiazem: the risk of developing myopathy and rhabdomyolysis increases with the combined use of diltiazem and simvastatin at a dose of 80 mg. With the simultaneous use of diltiazem and simvastatin in a dose of 40 mg, the risk of developing myopathy did not increase. The dose of simvastatin should not exceed 10 mg per day in patients using the drug with diltiazem simultaneously, if the clinical benefit exceeds the risk of myopathy and rhabdomyolysis.

Flucoidasp: rare cases of rhabdomyolysis associated with simultaneous use of simvastatin and fluconazole have been reported.

Ranolazin: cases of development of rhabdomyolysis with simultaneous application of ranolazine and simvastatin have been described. Colestyramia and colestipol reduce bioavailability (the use of simvastatin is possible 4 hours after the administration of these drugs, with an additive effect noted).

In two clinical trials, one involving healthy volunteers and the other with patients with hypercholesterolemia, simvastatin in a dose of 20-40 mg / day moderately enhanced the action of coumarin anticoagulants. The international normalized ratio (INR) increased from 1.7-1.8 to 2.6-3.4 in healthy volunteers and patients, respectively. In patients using coumarin anticoagulants, prothrombin time (or INR) should be determined before treatment and often at the initial stage of treatment with simvastatin to ensure no significant changes in prothrombin time (or INR). After establishing a stable prothrombin time (or MNO), it can be monitored at time intervals recommended for patients taking coumarin anticoagulants. When changing the dose of simvastatin, or interrupting treatment, the frequency of control of the protivobin time (or MNO) should be increased. The occurrence of bleeding or a change in prothrombin time (or INR) in patients not using anticoagulants is not associated with the use of simvastatin.

When combined simvastatin helps increase the concentration of digoxin in the blood plasma.

Colchicine: There are reports of the development of myopathy / rhabdomyolysis with the simultaneous use of colchicine and simvastatin in patients with renal insufficiency.

Rifampicin: since rifampicin is a strong inducer of the isoenzyme CYP3A4, in patients taking this drug for a long time (for example, in the treatment of tuberculosis), there may be a lack of efficacy of the use of simvastatin (lack of achievement of the target cholesterol concentration in the blood plasma). Grapefruit juice contains one or more components that inhibit the CYP3A4 isoenzyme and can increase the concentration in the blood plasma of substances metabolized by the CYP3A4 isoenzyme. An increase in the activity of HMG-CoA reductase inhibitors after consuming 250 ml of juice per day is minimal (an increase of 13% in the activity of HMG-CoA reductase inhibitors, estimating the area under the concentration-time curve) 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 reductasein the blood plasma. In this regard, it is necessary to avoid the consumption of grapefruit juice in large quantities. Simvastatin does not have an inhibitory effect on the isoenzyme CYP3A4. Therefore, it is assumed that simvastatin does not affect the plasma concentration of substances metabolized by the CYP3A4 isoenzyme.

Special instructions:At the beginning of drug therapy Simvastatin possibly a transient increase in the activity of "hepatic" enzymes.

Before the start of therapy, the liver function should be monitored regularly (to monitor the activity of liver enzymes every 6 weeks for the first 3 months, then every 8 weeks for the remaining first year and then for every six months), and also with increasing doses carry out a test to determine the function of the liver. When the dose is raised to 80 mg, a test should be performed every 3 months. With a persistent increase in the activity of transamiaas (3-fold compared with the baseline level), the preparation of Simvastatia should be stopped! ..

Simvastatii, like other inhibitors of HMG-CoA reductase, should not be used at an increased risk of rhabdomyolysis and renal insufficiency (against a background of severe acute infection, arterial hypotension, planned large surgery, trauma,severe metabolic disorders).

In patients with reduced thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome) with increasing cholesterol concentration, the first underlying disease should be performed first!

Preparation Simvastati with caution appoint to patients who abuse alcohol and / or have a history of liver disease.

Before and during treatment, the patient should be on a hypocholesterol diet.

Simultaneous reception of grapefruit juice can increase the severity of side effects associated with taking the drug Simvastaty, so you should avoid their simultaneous administration. Simvastatii is not indicated in cases where there is hypertriglyceridemia of types I and V.

The drug Simvastati increases the concentration of glucose in the blood plasma, therefore, in some patients at risk of diabetes, hyperglycemia may occur, requiring medical correction. However, reducing the risk of vascular complications with statins is greater than the risk of hyperglycaemia, therefore, when increasing blood glucose concentration, do not discontinue treatment with Simvastatia.The use of the drug in patients at risk (fasting blood glucose 5,6-6,9 mmol / l, body mass index more than 30 kg / m ', increased plasma concentration' GG, arterial hypertension) is possible with careful monitoring by a doctor.

With prolonged use of statins in rare cases, the development of interstitial lung disease (dyspnea, dry cough, worsening of the general state of health - increased fatigue, weight loss, chills) is possible. With the development of these symptoms, it is necessary to immediately stop the use of the drug Simvastatin.

Treatment with drug Simvastatin can cause myopathy, leading to rhabdomyolysis and kidney failure. The risk of this pathology increases in patients receiving simultaneously with Simvastatin one or more of the following medicines: fibrates (gemfibroblast, fenofibrate), ciclosporin, nefazadone, macrolides (erythromycin, clarithromycin), antifungal agents from the group of "azoles" (ketoconazole, itracoazol), HIV protease inhibitors (ritonavir), preparations containing a co-bicystate.The risk of myopathy is also increased in patients with severe renal failure.

All patients starting therapy with the drug Simvastatin, as well as patients who need to increase the dose of the drug, should be warned about the possibility of myopathy and the need to immediately seek medical attention in the event of unexplained pain, muscle soreness, lethargy or muscle weakness, especially if accompanied by malaise or fever. The drug should be discontinued immediately if mnatin is diagnosed or suspected.

In order to diagnose the development of myopathy, it is recommended to regularly evaluate the activity of CK.

When treating the drug Simvastatin it is possible to increase the activity of CK, which should be taken into account in the differential diagnosis of chest pain. The criterion for the discontinuation of the drug is an increase in the activity of CK more than 10 times the upper limit of the norm. In patients with myalgia, myasthenia gravis and / or marked increase in the activity of CKK, treatment with the drug is stopped.

The safety and efficacy of the drug 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 one year after the menarche. In patients of child age, who used simvastatin. the side-effect profile was similar to that of patients taking placebo. The use of simvastatin in a dose of more than 40 mg in children was not studied. In this study, there was no effect of the drug on the growth and puberty of young men and girls or any effect on the length of the menstrual cycle in girls.

The use of simvastatin has not been studied in children less than 10 years old and in girls 10-17 years before menarche.

The drug is effective both in monotherapy and in combination with sequestrants of bile acids.

If the current dose is skipped, the drug should be taken as soon as possible. If it's time for the next dose, do not double the dose.

Patients with severe renal failure receive iodine for renal function (see "With caution").

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.

When using simvastatin 80 mg / day in elderly patients (over 65 years), the risk of developing myopathy increases compared with patients younger than 65 years.

Duration of the drug is determined individually by the attending physician.

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

Impact on the ability to drive vehicles and mechanisms

During the period of drug treatment Simvastatin there may be side effects from the nervous system such as: headache, dizziness, muscle cramps, blurred vision, paresthesia. Therefore, care should be taken when driving vehicles and performing other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions

Form release / dosage:

Tablets, film-coated, 10 mg and 20 mg.

10, 15, 20 or 30 tablets in a planar cell packaging made of a polyvinylchloride film and aluminum foil.

15 or 30 tablets in a can of high-density polyethylene.

2 or 3 contourcell packs of 10 tablets, 1, 2, 4 or 6 contiguous cell packs but 15 tablets, 1, 2 or 3 contiguous cell packs but 20 tablets, 1, 2 or 3 contour packs of 30 tablets or one pot together with instructions for medical use in a pack of cardboard.

For hospitals

8 outline cell packs of 30 tablets together with an equal number of instructions for medical use or 16 contiguous cell packs of 15 tablets together with an equal number of instructions for medical use in a pack of cardboard

Packaging:

10, 15, 20 or 30 tablets in a planar cell packaging made of a polyvinylchloride film and aluminum foil.

15 or 30 tablets in a can of high-density polyethylene.

For hospitals

8 outline cell packs of 30 tablets together with an equal number of instructionsfor medical use or 16 contiguous cell packs of 15 tablets together with an equal number of instructions for medical use in a pack of cardboard

Storage conditions:In the dark place at a temperature of no higher than 25C.

Terms of leave from pharmacies:On prescription

Registration number:LSR-005377/07

Date of registration:26.12.2007

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Representation: & nbspVERTEKS CJSC VERTEKS CJSC Russia

Information update date: & nbsp29.07.2015

Illustrated instructions

Instructions

Simvastatin (Simvastatin)