Expiration date: 08/2025

The composition and form of issue:

Tablets, film-coated. 1 tablet contains:

simvastatin 5, 10, 20 or 40 mg

excipients: lactose starch MCC pregelatinization of hyprolose nizkosoleva butylhydroxyanisole magnesium stearate 

the shell: Opadry yellow OY-LS-52901 (tablets 5 mg), Opadry light pink OY-LS-54901 (for tablets of 10 mg) brown Opadry OY-LS-56504 (tablets 20 mg), Opadry pink OY-LS -54902 (tablets 40 mg) 

blistere in 10 PCs., in box 1, 3 or 10 blisters.

Description pharmaceutical form:

Tablets 5 mg: yellow, biconvex, oval, film-coated, engraved with "SST" on one side and "5" on the other side.

Tablets 10 mg: pinkish-white, biconvex, oval, film-coated, engraved with "SST" on one side and "10" on the other side.

Tablet 20 mg: light pink, biconvex, oval, film-coated, engraved with "SST" on one side and "20" on the other side.

Pills 40 mg: pink, biconvex, oval, film-coated, engraved with "SST" on one side and "40" on the other side.

Pharmacokinetics:

Absorption of simvastatin is high. Once inside the maximum concentration in plasma is reached after about 1,3–2,4 h is reduced by 90% after 12 hours Linking plasma protein is 95%.

Metabolized in the liver, has a first pass effect through the liver (hydrolyses education active derivative — beta-hydroxy acids found with other active and inactive metabolites). T1/2 active metabolites is 1.9 h.

It is excreted mainly with feces (60%) as metabolites. About 10-15% is excreted by the kidneys in an inactive form.

Description pharmacological action:

Lipid-lowering means, obtained synthetically from a fermentation product of Aspergillus terreus. Inactive lactone, the body is subjected to hydrolysis with the formation of gidrokshikislota derived.

The active metabolite inhibits 3-hydroxy-3-methyl-glutaryl-COA reductase (HMG-COA reductase) that catalyze the initial reaction is the formation of mevalonate from HMG-COA. Because the conversion of HMG-COA to mevalonate is an early step of cholesterol synthesis, the use of simvastatin does not cause accumulation in the body of potentially toxic sterols. HMG-Koa easily metabolized to acetyl-COA, which is involved in many synthetic processes in the body.

Reduces the content of triglycerides (TG), LDL, lipoprotein very low density (VLDL) and total cholesterol in plasma (in cases of heterozygous familial and non-family forms of hypercholesterolemia, with mixed hyperlipidemia, when high cholesterol is a risk factor). Increases LPVP content and reduces the ratio of LDL/HDL and total cholesterol/HDL.

The effect appears after 2 weeks from the beginning of reception, the maximum therapeutic effect is achieved after 4-6 weeks. The effect persists with continued treatment once the therapy cholesterol gradually returning to baseline (prior to treatment).

Indications:

Hypercholesterolemia:

• primary hypercholesterolemia (type IIa and IIb) the ineffectiveness of dietary low in cholesterol and other non-pharmacological interventions (physical activity and weight loss) in patients with increased risk of coronary atherosclerosis
  
• combined giperholesterinemia and gipertriglitzeridemia, not corrected by a special diet and exercise.
  

Coronary heart disease:

• prevention of myocardial infarction
  
• reducing the risk of death
  
• reducing the risk of cardiovascular disorders (stroke or transient ischemic attacks)
  
• slow the progression of coronary atherosclerosis
  
• reducing the risk of revascularization.
  

Contraindications:

• hypersensitivity to simvastatin or to other components of the drug and to other drugs statinovogo series (inhibitors of HMG-COA reductase) in history
  
• liver disease in the active phase, persistent increase in liver enzymes of unknown etiology
  
• porphyria
  
• diseases of skeletal muscles (myopathy)
  
• the age of 18 years (efficacy and safety not established).
  

With caution:

• patients who abuse alcohol
  
• patients after organ transplantation who have undergone the therapy immunodepressantami (due to the increased risk of rabdomioliza and kidney failure)
  
• condition that can lead to the development of severe insufficiency of the kidney ( arterial hypotension, acute infectious diseases heavy currents, expressed metabolic and endocrine disorders, violations vodno-elektrolitnogo balance, surgical interventions including dental, or injury)
  
• patients with low or high tone skeletal muscles unclear etiology
  
• epilepsy.
  

Application of pregnancy and breast-feeding:

Simvor is contraindicated in pregnant women. There have been some reports about the development of anomalies in newborns, mothers who took simvastatin.

Women of childbearing age taking simvastatin should avoid conception. If the treatment process pregnancy does occur, Simvor should be abolished and the woman should be warned about the potential hazard to the fetus.

Data on the allocation of simvastatin with maternal milk is not available. If necessary, the appointment of the drug Simvor in the lactation period should take into account that many medicines are excreted in breast milk, and there is a threat of severe reactions, therefore, breast-feeding while taking medication is not recommended.

Side effects:

Digestive system: possible abdominal pain, constipation, flatulence, nausea, diarrhea, pancreatitis, vomiting, hepatitis, increased liver enzymes, alkaline phosphatase, and creatine phosphokinase (CPK).

Nervous system and sensory organs: asthenic syndrome, headache, dizziness, insomnia, muscle cramps, paresthesia, peripheral neuropathy, blurred vision, impaired taste sensation.

Allergic and immunopathological reactions: angioneurotic edema, rheumatic polimialgia, vasculitis, thrombocytopenia, increased ESR, fever, arthritis, urticaria, photosensitivity, flushing of skin, hot flashes, shortness of breath. volchanochnopodobny syndrome, eosinophilia.

Dermatological reactions: rarely skin rash, itching, alopecia, dermatomyositis.

From the musculoskeletal: myopathy, myalgia, muscle cramps, weakness rarely — rhabdomyolysis.

Other: anemia, heartbeat, acute renal failure (due to rhabdomyolysis), low potency.

Drug interactions:

Cytostatics, antifungal agents (ketoconazole, Itraconazole), fibrates, high doses of nicotinic acid, immunosuppressants, erythromycin, clarithromycin, telithromycin, inhibitors of HIV protease, nefazodone increases the risk of myopathy.

Cyclosporine or danazol: the risk of myopathy/rhabdomyolysis is increased when administered together with cyclosporine or danazol, high doses of simvastatin.

Other lipid-lowering means to cause the development of myopathy the risk of myopathy is increased with a joint appointment with other lipid-lowering drugs that are not potent inhibitors of CYP3A4, but can cause myopathy in monotherapy conditions, such as gemfibrozil and other fibrates (except phenofibrate), and Niacin (nicotinic acid) at a dose of &ge1 g/day.

Amiodarone and verapamil: the risk of myopathy increases with coadministration of amiodarone or verapamil with high doses of simvastatin.

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

Simvastatin potentiates the action of oral anticoagulants (e.g. phenprocoumon, warfarin) and increases the risk of bleeding that requires monitoring of indicators of blood coagulation before treatment and regular monitoring in the initial period of therapy. Once achieved a stable level of PV or INR, further control should be spacing, recommended for patients receiving treatment with anticoagulants. If you change the dosage or stop taking the simvastatin also should be monitoring PV or INR according to the above scheme.

Therapy with simvastatin does not cause changes in PV and risk of bleeding in patients not taking anticoagulants.

Increases the level of digoxin in the blood plasma.

Cholestyramine and colestipol reduce the bioavailability (the use of simvastatin may 4 hours after taking the medicines, while there is a additive syndrome).

Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase the concentration in blood plasma means metabolized CYP3A4.

Increased activity of inhibitors of HMG-COA reductase after drinking 250 ml of juice a day is minimal and has no clinical significance. However, the consumption of a large amount of juice (more 1 l a day) while taking simvastatin significantly increases the level of inhibitory activity against HMG-COA reductase in the blood plasma. In this regard, you must avoid drinking grapefruit juice in large quantities.

Method of application and dose:

Inside, 1 times per day in the evening, squeezed enough water, regardless of meals.

Before starting treatment with the drug Simvor the patient should be assigned a standard gipoholesterinovu diet that must be adhered to throughout the course of treatment.

The recommended dose of the drug Simvor for the treatment of hypercholesterolemia ranges from 10 to 80 mg 1 times a day in the evening. The recommended initial dose for patients with hypercholesterolemia, is 10 mg.

The maximum daily dose — 80 mg.

Changes (selection) the dose should be carried out at intervals of 4 weeks. In most patients the optimal effect is achieved when taking the drug in doses up to 20 mg/day.

Patients with homozygous hereditary hypercholesterolemia the recommended daily dose of the drug Simvor is 40 mg 1 time per day or evening 80 mg 3 reception (20 mg in the morning and 40 mg in the evening).

When treating patients with CHD or high risk of coronary heart disease, effective doses of the drug Simvor make up 20-40 mg/day. Therefore, the recommended initial dose in such patients — 20 mg/day. Change (selection) the dose should be carried out at intervals of 4 weeks, the dose can be increased to 40 mg/day. If the content of LDL cholesterol less than 75 mg/DL (1,94 mmol/l), total cholesterol less than 140 mg/DL (3.6 mmol/l), the dose should be reduced.

Patients of advanced age or with renal insufficiency mild or moderate degree of change dosage not required.

Patients with chronic renal failure (Cl creatinine less than 30 ml/min) or receiving ciclosporin, fibrates, danazol, gemfibrozil or other fibrates (except phenofibrate), Niacin in doses that reduce the lipid content, (&ge1 g/day), the maximum recommended dose of the drug Simvor should not exceed 10 mg/day.

The daily dose of the drug Simvor in patients receiving simultaneously with amiodarone or verapamil should not exceed 20 mg.

Overdose:

None of the few known cases of overdose (maximum approved dose of 450 mg) specific symptoms have been identified.

Treatment: induction vomiting, the appointment of activated carbon. Symptomatic therapy. Should monitor liver and kidneys, the CPK level in the blood serum.

In the development of myo with rhabdomyolysis and acute renal failure (rare but severe side effect) should immediately stop taking the drug and enter patient diuretic and sodium bicarbonate (in/in cefuroxim). If necessary, shown hemodialysis.

Rhabdomyolysis can cause giperkaliemia, that can be resolved/with the introduction of calcium chloride and calcium gluconate, infusion of glucose with insulin, the use of potassium ion-exchangers or, in severe cases, using hemodialysis.

Special instructions:

At the beginning of therapy drug Simvor may challenge elevated liver enzymes.

Before starting therapy and then regularly should be the study of the liver (control the activity of liver enzymes every 6 weeks for the first 3 months, then every 8 weeks during the remainder of the first year and then 1 every six months). At higher doses, it is necessary to conduct a test to determine liver function. If the dose to 80 mg is required to test every 3 months. The steady increase in the activity of transminase (3 times compared to the initial level) the drug Simvor should be discontinued.

Singer, like other inhibitors of HMG-COA reductase, it should not be used in high risk of rabdomioliza and kidney failure (against the backdrop of severe acute infections, arterial hypotension, planned a big surgery, injuries, severe metabolic disorders).

Cancellation of lipid-lowering drugs during pregnancy has no significant effect on the results of prolonged treatment of primary hypercholesterolemia.

Due to the fact that inhibitors of HMG-COA reductase to inhibit cholesterol synthesis, and cholesterol and other products of its synthesis play an essential role in fetal development, including synthesis of steroids and cell membranes, simvastatin can have adverse effects on the fetus in the appointment of his pregnant women (women of reproductive age should avoid conception). If in the process of treatment there is a pregnancy, the drug should be withdrawn, and the woman warned of the possible danger to the fetus.

The use of the drug Simvor is not recommended in women of childbearing age not using contraceptives.

In patients with reduced thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome) when cholesterol, you should first treat the underlying disease that caused hypercholesterolemia.

Simvor prescribed with caution in individuals who abuse alcohol and/or have a history of liver disease.

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

Simultaneous intake of grapefruit juice may increase the severity of side effects associated with taking the drug Simvor, so you should avoid their simultaneous reception.

In patients with myalgia, myasthenia and/or expressed by increased activity of KFK treatment with the drug is stopped. Simvor not shown in cases when there is gipertriglitzeridemia I, IV and V types.

Treatment with Simvor can cause myopathy, leading to rhabdomyolysis and renal failure. The risk of this disease increases in patients, receiving simultaneously with the drug Simvor one or more of the following drugs: fibrates (gemfibrozil), cyclosporine, nefazodone, macrolides (erythromycin, clarithromycin), antifungal agents from the group of azoles (ketoconazole, Itraconazole) and HIV protease inhibitors (ritonavir). The risk of myopathy increases in patients with severe renal insufficiency.

All patients starting therapy with the drug Simvor, and patients who need to increase the dose of the drug should be warned about the possibility of myopathy and need immediate treatment to the doctor in case of unexplained pain, soreness in muscles, lethargy or muscle weakness, particularly if accompanied by malaise or fever. Therapy with the drug should be immediately discontinued if myopathy is diagnosed or suspected.

In order to diagnosis of myopathy is recommended regularly measuring the value of CPK.

In the treatment of drug Simvor is possible to increase the content of serum CPK, that should be considered in the differential diagnosis of pain behind the breastbone. Criterion for drug withdrawal is the increase in levels of creatine kinase in the serum of more than 10 times the upper limit of normal.

Effective as monotherapy and in combination with bile acid resins.

If you skip doses of the drug must be taken as soon as possible. If it is time for your next dose, the dose is not doubled.

Patients with severe renal insufficiency treatment to control kidney function.

The duration of the drug is determined by the attending physician individually.

Effects on ability to drive and operate machinery. About the adverse effect of the drug Simvor on the ability to drive and work with mechanisms not reported.