Expiration date: 06/2025

The composition and form of issue:

Tablets, film-coated. 1 tablet contains simvastatin 10 or 20 mg

excipients: lactose monohydrate acid ascorbic acid citric monohydrate MCC PH 101 starch pregelatinization butylhydroxyanisole magnesium stearate Opadry 33G24737 (table. 10 mg) or Opadry 39G22514 (table. 20 mg) 

in a contour acheikova packing 14 PCs. in cardboard pack 1 or 2 packs.

Description pharmaceutical form:

Tablets 10 mg: pink tablets, film-coated, round, homogeneous, solid with edges. The cut visible 2 layer - uniformly white with a thin pink coating on the edge of the core.

Tablets 20 mg: yellow tablets, film-coated, round, homogeneous, solid with edges. The cut visible 2 layer - uniformly white with a thin yellow coating at the edge of the core.

Feature:

Lipid-lowering means, obtained synthetically from a fermentation product of Aspergillus terreus.

Pharmacokinetics:

Absorption of simvastatin high. Once inside C max achieved through 1,3–2,4 h is reduced by 90% through 12 h. the Relationship with blood plasma proteins is 95%. Simvastatin is metabolized in the liver, has the effect of "first passage" through the liver (hydrolyzed to its active form beta-hydroxy acid, and other active and inactive metabolites). T1/2 active metabolites is 1.9 h. mostly excreted in feces (60%) as metabolites. About 10-15% is excreted by the kidneys in an inactive form.

Description pharmacological action:

Is an 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), the enzyme catalyzing the initial reaction of 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 a buildup of potentially toxic sterols. HMG-Koa easily metabolized to acetyl-COA, which is involved in many processes of synthesis in the body.

Simvastatin lowers the concentration in blood plasma triglycerides, LDL, VLDL and total cholesterol (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 onset of effect after 2 weeks from the beginning of reception, the maximum therapeutic effect is achieved after 4-6 weeks. The effect persists with continued treatment, at the termination of a therapy cholesterol gradually returning to the initial level.

Indications:

• primary hypercholesterolemia (type IIa and IIb) with poor diet 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 amenable to correction special diet and physical activity
  
• prevention of myocardial infarction
  
• reducing the risk of death and the risk of cardiovascular disorders (stroke or transient ischemic attacks) in CHD
  
• slow the progression of coronary atherosclerosis
  
• reducing risk in 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 deficiency of kidney, such as hypotension, acute infectious diseases heavy currents, expressed metabolic and endocrine disorders, violations vodno-electrolytic balance, surgical interventions (including dental), or injury
  
• patients with low or high tone skeletal muscles unclear etiology
  
• epilepsy.
  

Application of pregnancy and breast-feeding:

Simvastol 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, Simvastol 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 Simvastol in the breastfeeding period should take into account that many drugs are excreted in breast milk and there is a threat of severe reactions, therefore, breast-feeding while taking medication is not recommended.

Side effects:

From the digestive system: possible abdominal pain, constipation or diarrhoea, flatulence, nausea, vomiting, pancreatitis, hepatitis, increased liver enzymes, alkaline phosphatase, and creatine phosphokinase (CPK).

From the nervous system and sensory organs: asthenic syndrome, headache, dizziness, insomnia, 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, muscle weakness and 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, HIV protease inhibitors, nefazodone — increase 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 when given alone, such as gemfibrozil and other fibrates (except phenofibrate), and Niacin (nicotinic acid) at a dose of &ge1 g per 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 quite often 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.

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

Simvastatin increases the level of digoxin in the blood plasma.

Cholestyramine and colestipol reduce the bioavailability (the use of simvastatin may through 4 h after administration of these drugs, showing an additive effect).

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, it is necessary to avoid consumption of grapefruit juice in large quantities.

Method of application and dose:

Before treatment Simvastol the patient should be assigned a standard gipoholesterinovu diet that must be adhered to throughout the course of treatment.

Inside, 1 time a day, in the evening, squeezed enough water. The drug should not be linked with food intake.

The recommended dose of Simvastol for the treatment of hypercholesterolemia ranges from 10 to 80 mg 1 time per day in the evening. The recommended initial dose for patients with hypercholesterolemia is 10 mg. Maximum daily dose of 80 mg.

Change (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.

In patients with homozygous hereditary hypercholesterolemia recommended daily dose Simvastol is 40 mg 1 time per day or evening 80 mg 3 reception (20 mg morning, 20 mg day and 40 mg in the evening).

In the treatment of patients with CHD or high risk for coronary heart disease effective dose of Simvastol 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), and total cholesterol — less than 140 mg/DL (3.6 mmol/l), the dose should be reduced.

In elderly patients and in patients with mild-to-moderately severe renal failure changes dosage not required.

In patients with chronic renal failure (Cl creatinine less than 30 ml/min) or receiving ciclosporin, danazol, gemfibrozil or other fibrates (except phenofibrate), nicotinic acid lepidotrigla doses (&ge1 g/day) in combination with simvastatin, the maximum recommended dose Simvastol should not exceed 10 mg/day.

For patients taking amiodarone or verapamil simultaneously with Simvastain, the daily dose should not exceed 20 mg.

Overdose:

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

Treatment: induce vomiting, take activated charcoal, symptomatic therapy. Should monitor liver function and kidney, the level of CPK in the 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 or 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 Simvastol the transient increase in liver enzymes.

Before therapy and then should regularly carry out 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, at higher doses up to 80 mg are required to test every 3 months. When persistent elevations of transaminases (3 times the baseline level) reception Simvastol should be discontinued.

Simvastol, 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 during treatment should avoid conception). If in the process of pregnancy, the drug should be withdrawn, and the woman warned of the possible danger to the fetus.

Application Simvastol 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.

Simvastol 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 Simwastol.

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

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

All patients starting therapy Simvastol, 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 Simvastol 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.

The drug is 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.

A detrimental effect of Simvastol on the ability to drive and work with mechanisms not reported.