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

In 1 tablet, coated with a coating, with a dosage of 10 mg, contains: active substance simvastatin - 10 mg; auxiliary substances: corn starch - 20 mg, lactose monohydrate - 95.18 mg, microcrystalline cellulose - 10 mg, butyl hydroxy anisole - 0.02 mg, ascorbic acid - 2.5 mg, citric acid - 1.3 mg, magnesium stearate - 1 mg, Opadrai II white (macrogol (polyethylene glycol), polyvinyl alcohol, talc, titanium dioxide) 4.2 mg.

In 1 tablet, coated with a coating, with a dosage of 20 mg, contains: active substance simvastatin - 20 mg; auxiliary substances: corn starch - 40 mg, lactose monohydrate - 190.46 mg, microcrystalline cellulose - 20 mg,Butyl hydroxy anisole - 0.04 mg, ascorbic acid 5 mg, citric acid 2.5 mg, magnesium stearate 2 mg, Opadrai II yellow (macrogol (polyethylene glycol), polyvinyl alcohol, quinoline yellow aluminum lacquer, talc, titanium dioxide, oxide iron yellow) - 8.4 mg

Description:

Tablets 10 mg - round biconcave, coated with a coat of white. ¹Tablets of 20 mg - round biconcave, coated with a yellow 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 is metabolized 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, 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 the plasma levels of triglycerides (TG), low-density lipoproteins (LDL), very low density lipoproteins (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 of high density lipoprotein (HDL) and reduces the ratio of LDL / HDL and total cholesterol / HDL.

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 cholesterol content gradually returns to the baseline level.

Pharmacokinetics:

Absorption of simvastatin is high. 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 a "first pass" through the liver (hydrolyses to form an active derivative: beta-hydroxy acid, other active,as well as inactive metabolites). The half-life of active metabolites is 1.9 hours.

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

Indications:

Hypercholesterolemia:

primary hypercholesterolemia (type Pa and IIIb) with ineffectiveness of diet with low cholesterol and other non-drug measures (physical activity and weight loss) in patients with an increased risk of coronary atherosclerosis;
combined hypercholesterolemia and hypertriglyceridemia, not corrected by a special diet and exercise.
Homozygous hereditary hypercholesterolemia.

Cardiac ischemia:

for the prevention of myocardial infarction, to reduce the risk of death, reduce the risk of cardiovascular disorders (stroke or transient ischemic attacks), slow the progression of coronary artery atherosclerosis, reduce the risk of revascularization procedures.

Contraindications:

Hypersensitivity to simvastatiyu and / or auxiliary components of the drug,as well as to other drugs of the statin series (inhibitors of HMG-CoA reductase) in the anamnesis;
hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption;
liver disease in the active phase, persistent activity increase "hepatic" traysaminases in the blood plasma of an unclear etiology;

concomitant treatment with strong inhibitors of isoenzyme CYP3A4 (itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, and preparations containing kobitsystat) (see section "Interaction with other medicinal products").

preparations ");
- concomitant treatment gemfibrozil, cyclosporin or danazol;
- diseases of skeletal muscles (myopathy);
- age under 18 years (effectiveness and safety not established);
- pregnancy, period of breast feeding, use in women of reproductive age, not using reliable methods of contraception.

Carefully:

prescribed to patients who abuse alcohol, patients after

transplantation of organs undergoing immunosuppressant therapy (in connection with

increased risk of rhabdomyolysis and renal failure); at

conditions that can lead to the development of severe renal failure, such as arterial hypotension, acute infectious diseases of severe course, severe metabolic and endocrine disorders, water-electrolyte balance disorders, surgical interventions (including dental), or trauma; patients with decreased or increased tone of skeletal muscles of unknown etiology; epilepsy; liver disease in anamnesis.

Pregnancy and lactation:

Simvastatin is contraindicated in pregnancy. There are several reports of the development of anomalies in newborns whose mothers were taking simvastatin.

Women of childbearing age who receive simvastatin, should avoid conception. If in the course of treatment the pregnancy nevertheless has come, Simvastatin should be canceled, and a woman should be warned about the possible danger to the fetus. Data on the isolation of simvastatin with mother's 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 taking the drug is not recommended.

Dosing and Administration:

Before the treatment with Simvastatin, the patient should be prescribed a standard hypocholesterol diet, which should be observed throughout the course of treatment.

Simvastatin should be taken 1 time per day in the evening, with plenty of water.

The time of taking the drug should not be associated with eating.

Recommended dose Simvastatin for treatment hypercholesterolemia varies from 10 to 80 mg once a day in the evening. The recommended initial dose of the drug for patients with hypercholesterolemia is 10 mg. The maximum daily dose is 80 mg. Changes (selection) of the dose should be carried out at intervals of 4 weeks. Have most patients the optimal effect is achieved when taking the drug in doses up to 20 mg per day.

Have patients with homozygous hereditary hypercholesterolemia the recommended daily dose of Simvastatin is 40 mg once a day in the evening or 80 mg in three divided doses (20 mg in the morning, 20 mg in the afternoon and 40 mg in the evening).

In the treatment of patients from ischemic heart disease (CHD) or high-risk

development of IHD effective doses of simvastatin are 20-40 mg per day. Therefore, the recommended initial dose in such patients is 20 mg per day.Changes (selection) of the dose should be carried out at intervals of 4 weeks, if necessary, the dose can be increased to 40 mg per day. If the LDL content is less than 75 mg / dL (1.94 mmol / L), the total cholesterol content is less than 140 mg / dl (3.6 mmol / L), the dose of the drug should be reduced.

Have elderly patients and in patients with mild or moderate degree renal insufficiency no change in dosage is required.

In patients with chronic renal failure (creatinine clearance less than 30 ml / min) or receiving ciclosporin, danazol, gemfibrozil or other fibrates (except fenofibrate), niacin in lipid-lowering doses (> 1 g / day) in combination with simvastatin, the maximum recommended dose of simvastatin should not exceed 10 mg per day.

For patients receiving amiodarone or verapamil Simvastatin should not exceed 20 mg daily.

Side effects:

Digestive system: abdominal pain, constipation, flatulence, nausea, diarrhea, pancreatitis, vomiting, hepatitis, increased activity of "liver" enzymes, alkaline phosphokinase and creatine phosphokinase (CKF).

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

Allergic and immunopathological reactions: angioedema,

Rheumatic polymyalgia, vasculitis, thrombocytopenia, increased ESR,

fever, arthritis, urticaria, photosensitivity, skin hyperemia, hot flashes, dyspnea, lupus-like syndrome, eosinophilia.

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

From the musculoskeletal system: Myopathy, myalgia, muscle cramps, weakness; rarely rhabdomyolysis.

Other: Anemia, palpitation, acute renal failure (due to

rhabdomyolysis), decreased potency.

Overdose:

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

Treatment: induce vomiting, take Activated carbon. Symptomatic therapy. It is necessary to monitor the liver and kidney function, the level of CK in the blood serum.

With the development of myopathy with rhabdomyolysis and acute renal failure (a rare but severe side effect), the drug should be stopped immediately and the diuretic and sodium bicarbonate (intravenous infusion) administered to the patient. If necessary, hemodialysis is indicated.

Rhabdomyolysis can cause hyperkalemia, which can be eliminated by intravenous administration of calcium chloride or calcium gluconate, glucose infusion with insulin, potassium ion exchangers or, in severe cases, hemodialysis.

Interaction:RThe development of myopathy / rhabdomyolysis increases with simultaneous use of simvastatin with following preparations: Contraindications

ANDinhibitors of isoenzyme CYP3A4

Contraindicated concomitant treatment with strong inhibitors of isoenzyme CYP3A4: itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, bocetrevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, and preparations containing the co-bicarbonate (see "Contraindications"). If treatment with these drugs can not be avoided, treatment with simvastatin should be interrupted for the period of their use.

Gemfibrozil, ciclosporin, danazol.

Simultaneous use of these drugs and simvastatin is contraindicated (see section "Contraindications").

Other drugs

Cytostatics, immunosuppressants, a nicotinic acid in a dose of more than 1 g / day: simultaneous use of simvastatin with these drugs increases pclaim of myopathy / rhabdomyolysis.

Other hypolipidemic drugs that can cause the development of myopathy: the risk of myopathy increases with the joint appointment of simvastatin with other lipid-lowering drugs that are not strong inhibitors CYP3A4, but are capable of causing myopathy under conditions of monotherapy.

Other fibrates: the patients taking fibrates other than gemfibrozil (see the section "Contraindications") the recommended dose of simvastatin should not exceed 10 mg per day. A nicotinic acid: the patients receiving simvastatin and nicotinic acid in lipid-lowering doses (> 1 g / day), the recommended dose of simvastatin should not exceed 10 mg per day.

Amiodarone: the patients receiving amiodarone, the dose of simvastatin should not exceed 20 mg per day.

Dronedaron: in patients taking dronedaron, the dose of simvastatin should not exceed 10 mg per day.

Blocks of "slow" calcium channels

Verapamil and diltiazem: in patients taking verapamil or diltiazem, the dose of simvastatin should not exceed 10 mg per day. Amlodipine: in patients taking amlodipine, the dose of simvastatin should not exceed 20 mg per day.

Ranolazine: the patients receiving ranolazine, the dose of simvastatin should not exceed 20 mg per day.

Indirect anticoagulants (eg fenprocumone, warfarin) Simvastatin potentiates the action oral anticoagulants (for example, 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.

TOAs soon as a stable prothrombin time indicator or International Normalized Ratio (MNO) is reached, its further control should be carried out at intervals,

recommended for patients receiving therapy

anticoagulants. When changing the dosage or stopping the intake of simvastatin, it is also necessary to monitor prothrombin time or INR according to 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. Digoxip

With simultaneous application simvastatin increases the concentration of digoxin in the blood plasma.

Fusidic acid, colchicine

Simultaneous application simvastatin with fusidic acid or colchicine increases the risk of myopathy.

Kolestyramine and colestipol

reduce bioavailability withImvastatin (Simvastatin administration is possible 4 hours after taking these

medicinal preparations, while there is an additive effect).

Grapefruit juice contains one or more components that inhibit the isoenzyme CYP3A4 and can increase the concentration in blood plasma of drugs,

metabolized by 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 Simvastatin significantly increases the level of inhibitory activity against HMG-CoA reductase in blood plasma.In this regard, it is necessary to avoid the consumption of grapefruit juice in large quantities.

Special instructions:

At the beginning of Simvastatin therapy, a transient increase in aactivity of "liver" transaminases. Before starting therapy, continue to conduct regular liver function tests (monitor the activity of "liver" transaminases every 6 weeks for the first 3 months, then every 8 weeks for the remainder of the first year, and then 1 time in six months), and when 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 "liver" transaminases (3-fold compared with the baseline level), Simvastatin should be discontinued. Simvastatin, as well as other inhibitors of HMG-CoA reductase, should not be used at an increased risk of rhabdomyolysis and renal insufficiency (against severe acute infection, arterial hypotension, planned large surgery, trauma, severe metabolic disorders). Abolition of lipid loweringduring pregnancy does not have a significant effect on the results of long-term treatment of primary hypercholesterolemia.

In patients with a decreased thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome), when the concentration of cholesterol is increased, the underlying disease must first be treated. Simvastatin 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 simvastatin, therefore, one should avoid their simultaneous administration.

Simvastatin is not indicated in cases where there is hypertriglyceridemia I, IV and V types.

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

Treatment with simvastatin can cause myopathy, leading to rhabdomyolysis and kidney failure.

The risk of this pathology increases in patients with severe renal failure, in elderly patients (over the age of 65), female patients,patients with uncontrolled hyperthyroidism, as well as in patients receiving simvastatin simultaneously with one or more of the following medicines: fibrates (gemfibrozil, fenofibrate), ciclosporin, danazol, nefazadone, macrolides (erythromycin, clarithromycin), antifungal agents from the group "azoles" (ketokenazole, intraconazole, posaconazole, voriconazole), HIV protease inhibitors (ritonavir, buprenavir, telaprevir) or nPreparations containing a cobicystate (see the sections "Contraindications", "Interaction with other

medicinal products ").

In patients receiving simvastatin in a dose of 80 mg per day, the risk of developing myopathy is higher than with the use of other statins,

causing a comparable decrease in LDL cholesterol, therefore simvastatin at a dose of 80 mg per day should be prescribed only to patients at high risk for cardiovascular complications, in whom drug therapy at lower doses is not possible to achieve a therapeutic effect, and the intended use of the treatment exceeds the potential risk. All patients starting therapy with 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 andwhether muscle weakness, especially if it is accompanied by

malaise or fever. The drug should be discontinued immediately if myopathy is diagnosed or suspected.

In order to diagnose the development of myopathy, it is recommended to regularly measure the activity of CK. In the treatment with simvastatin, the activity of serum cytokine can be increased, which should be taken into account in differential diagnosis of chest pain. The criterion for the discontinuation of the drug is an increase in the activity of CK in the blood serum more than 10 times the upper limit of the norm. In patients with myalgia, myasthenia gravis and / or a marked increase in the activity of CKK, treatment with the drug is stopped. The drug is effective both in monotherapy and in combination with bile acid sequestrants.

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

Patients with severe renal failure receive treatment under the control of kidney function.Duration of the drug is determined individually by the attending physician.

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

The adverse effects of simvastatin on the ability to drive and work with machinery have not been reported.

Form release / dosage:

The tablets covered with a cover, on 10 and 20 mg. For 10 tablets in a contour mesh box made of PVC film and aluminum foil printed lacquered.

Packaging:

For 2, 3, 5 or 10 contour mesh packages together with the instructions for use are placed in a pack of cardboard.

Packing for hospitals. 100, 200, 300, 400 or 500 contour-cell packs with instructions for use are placed in boxes of corrugated cardboard. For 500, 1000 or 2000 tablets in cans of polymer with lids. By 1,2, 3, 4, 5, 6 cans with instructions for use in boxes made of corrugated cardboard.

Storage conditions:In dry, the dark place at a temperature of no higher than 30 ° C. Keep out of the reach of children!

Shelf life:2 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-003486/08

Date of registration:05.05.2008

The owner of the registration certificate:ZIO-HEALTH, JSC ZIO-HEALTH, JSC Russia

Manufacturer: & nbsp

ZIO-HEALTH, JSC Russia

Information update date: & nbsp01.08.2015

Illustrated instructions

Instructions

Simvastatin (Simvastatin)