Expiration date: 08/2025
The composition and form of issue:
Tablets, film-coated. 1 tablet contains:
simvastatin 5, 10, 20, 30 or 40 mg
excipients: maize starch lactose monohydrate microcrystalline ascorbic acid citric acid monohydrate magnesium stearate hypromellose talc titanium dioxide iron (III) oxide
blistere in 10 PCs. in cardboard pack 1, 2, 3, 4 or 5 blisters.
Description pharmaceutical form:
Tablets 5 mg: tablets are light yellow, film-coated, oval, convex, with a notch and an indication of "SIM 5" on one side.
Tablets 10 mg: tablets are light pink, film-coated, oval, convex, with a notch and an indication of "SIM 10" on one side.
Tablets 20 mg: tablets are light-orange, film-coated, oval, convex, with a notch and an indication of "SIM 20" on one side.
Tablets 30 mg: tablets white or almost white, film-coated, oval, convex, with a notch and an indication of "SIM 30" on one side.
Pills 40 mg: tablets are pink in colour, film-coated, oval, convex, with a notch and an indication of "SIM 40" on one side of the fracture a white color.
Feature:
Lipid-lowering means, obtained synthetically from a fermentation product of Aspergillus terreus, is an inactive lactone, in the body undergoes metabolism with the formation of gidrokshikislota derived.
Pharmacological action:
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.
Causes decrease in the content of plasma triglycerides (TG), low density lipoprotein (LDL), lipoproteins of very low density (VLDL) and total cholesterol (in cases of heterozygous familial and non-family forms of hypercholesterolemia mixed hyperlipidemia, when high cholesterol is a risk factor).
Increases the content of lipoproteins high density (HDL) and decreases the ratio of LDL/HDL and total cholesterol/HDL.
Pharmacokinetics:
Absorption of simvastatin high. Once inside C max in plasma is reached after about 1,3–2,4 h is reduced by 90% after 12 hours Linking blood plasma proteins is about 95%.
Metabolized in the liver. There is the effect of "first passage" through the liver (hydrolyses education active derivative — beta-hydroxy acids and other active and inactive metabolites). T1/2 active metabolites is 1.9 h.
It is excreted mainly with feces (60%) in the form of metabolites, about 10-15% in the kidneys inactive form.
Description pharmacological action:
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, at the termination of a therapy cholesterol gradually returning to the initial level.
Indications:
Hypercholesterolemia 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 exercise.
Coronary artery disease: prevention of myocardial infarction (secondary prevention of myocardial infarction) in patients with elevated cholesterol (>5.5 mmol/l).
Contraindications:
Hypersensitivity to simvastatin or to other components of the drug and to other drugs statinovogo number (inhibitors of HMG-CoA reductase inhibitors) history of liver failure, acute liver disease, persistent increase in liver transaminaz unclear etiology violation of the formation of red blood cells (porphyria) diseases of skeletal muscles (myopathy) concomitant use of ketoconazole, Itraconazole (antifungal drugs systemic), drugs for treatment of HIV infection pregnancy and breast-feeding.
Application of pregnancy and breast-feeding:
You should not take Simvahexal during pregnancy. 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 in the process of drug pregnancy does occur, it is necessary to cancel the admission of Simwagexala, 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 Simwagexala women in lactation 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:
Digestive system: possible abdominal pain, constipation, flatulence, nausea, diarrhea, dyspepsia, pancreatitis, vomiting, hepatitis, increase in liver transaminases, alkaline phosphokinase 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: rare — 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, itch, alopecia.
From the musculoskeletal: myopathy, myalgia, weakness rarely — rhabdomyolysis.
Other: anemia, heartbeat, acute renal failure (due to rhabdomyolysis), low potency.
Drug interactions:
Cytostatics, antifungal drugs (ketoconazole, Itraconazole), fibrates, high doses of nicotinic acid, immunosuppressants, erythromycin, clarithromycin, protease inhibitors increase the risk of rhabdomyolysis.
Leads to increased action of oral anticoagulants (e.g. phenprocoumon, warfarin) and increases the risk of bleeding that requires the need to monitor blood coagulability before treatment and regularly during treatment.
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).
Method of application and dose:
Inside, squeezed enough water, 1 time a day in the evening.
Hypercholesterolemia: depending on the severity of the NCEP initial dose of 5 to 10 mg/day. The dose is established on the basis of the level of cholesterol in plasma obtained with an interval of at least 4 weeks. The usual daily dose is 40 mg. With the lack of effectiveness and the presence of cardiovascular risk may be increased to a maximum dose before receiving 80 mg/day.
Coronary heart disease: initial dose of 20 mg, If necessary dose gradually increased every 4 weeks to 40 mg If the LDL 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.
For patients with chronic renal failure (Cl creatinine less than 30 ml/min) or simultaneously receiving cyclosporine, fibrates or Niacin, the initial dose of 5 mg, and the maximum allowed daily dose — 10 mg.
On the background of immunosuppressive therapy, the recommended initial dose of 5 mg/day, maximum daily dose of 5 mg/day.
Overdose:
None of the few known cases of overdose (maximum approved dose of 450 mg) specific symptoms have been identified.
Treatment: induce vomiting and use activated carbon. Symptomatic treatment: should be monitored liver and kidney, the level of creatine kinase in the serum.
Precautions:
Be wary appoint patients who abuse alcohol, patients after organ transplantation who have undergone the therapy immunodepressantami (due to the increased risk of rabdomioliza and kidney failure) when conditions that may lead to such a development of severe insufficiency of kidney function, as arterial hypertension, acute infectious diseases heavy currents, expressed metabolic and endocrine disorders, violations vodno-elektrolitnogo balance, surgical interventions (including dental), or injury to the patients with low or high tone skeletal muscles unclear etiology in epilepsy the age of 18 years (safety and efficacy not established).
Special instructions:
At the beginning of therapy with simvastatin the transient increase in liver enzymes (serum transaminase).
Before starting therapy and then regularly should be the study of the liver (monitor activity transaminaz liver every 6 weeks for the first 3 months, then every 8 weeks during the remainder of the first year and then 1 time a year), and at higher doses, it is necessary to conduct a test to determine liver function. With increasing doses up to 80 mg are required to test every 3 months. When persistent elevations of transaminases (3 times the baseline level) the admission of Simwagexala should be discontinued.
Simvahexal, 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 pregnancy, the drug should be withdrawn, and the woman warned of the possible danger to the fetus.
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.
Patients should inform the doctor about any manifestations on the part of the muscular system. In order to diagnosis of myopathy is recommended regularly measuring the value of CPK.
Be wary appoint persons who 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 the intake of Simwagexala, so avoid their joint reception.
In patients with myalgia, myasthenia and/or expressed by increased activity of KFK treatment with the drug is stopped. Simvahexal not shown in cases when there is gipertriglitzeridemia I, IV and V types.
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 should not be doubled.
Patients with severe renal insufficiency treatment to control kidney function.
The duration of the drug is determined by the attending physician individually.
