Simvastatin-SZ - instructions for use, dose, side effects, contraindications

Supplementary substances: ascorbic acid 2.5 mg, 5 mg, 10 mg, starch, potato, 20 mg, 40 mg, 80 mg, lactose monohydrate (milk sugar) 90 mg, 180 mg, 360 mg, microcrystalline cellulose - 10 mg, 20 mg; 40 mg, butyl hydroxy anisole -0.02 mg, 0.04 mg, 0.08 mg, citric acid 1.2 mg, 2.4 mg, 4.8 mg, magnesium stearate, 1.28 mg, 2, 56 mg, 5.12, mg / silicon: Colloidal dioxide (aerosil) 4 2, mg, 4 mg, 8 mg, talc -1 mg, 2 mg 4 mg;

composition of the shell: Opadrai II: (alcohol polyvinyl, partially hydrolyzed 4.16 mg, 3.2 mg, 6.4 mg, talc-'0.592 mg, 1.184 mg, 2.368 mg,macrogol (polyethylene glycol 3350) - 0.808 mg, -1.616 mg, 3.232 mg, .titanium dioxide E 171: 0.8748 mg, 1.7496 mg, 3.4992 mg, iron oxide color (II) yellow: E 172-0, 0012 mg, 0.0024 mg, .0.0048 'mg, aluminum lacquer based on dye quinoline yellow E104 - 0.1204 mg, 0.2408 mg, 0.4816 mg, aluminum lacquer on. based dye sunset yellow E 110 - 0.0028 mg, 0.0056 mg, 0.0112 mg, aluminum lignol based on indigo carmine E 132-0,0008 mg, 0.0016, mg, 0.0032 mg

Description:

Round biconvex tablets covered with a film coat from light yellow to yellow; The tablet is white or almost white in color.

Pharmacotherapeutic group:: a hypolipidemic agent - an inhibitor of HMG-CoA reductase

ATX: & nbsp

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

C.10.A.A.01 Simvastatin

Pharmacodynamics:The lipid-lowering agent obtained synthetically from the fermentation product of Aspergillus terreus is an inactive lactone in the body 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 catalyzing the initial reaction of the formation of mevalonate 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 accumulation in the body potentially,toxic-sterols HMG-CoA is easily metabolized to acetyl-CoA, which is involved in many synthesis processes in the body. Simvastatin causes a decrease in the plasma content of triglycerides '(TG),' low-density lipoproteins. (LDL) ,. lipoproteins are very low; Density (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) due to; inhibiting the synthesis of cholesterol in the liver and increasing the number of LDL receptors on the surface of cells, which leads to increased capture and catabolism of LDL; Increases the high-density lipoprotein (HDL) content and reduces .. the ratio of LDL / HDL and total cholesterol / HDL. Does not; mutagenic effect.

The onset of the effect is 2 weeks after the start of the treatment, and the maximum therapeutic effect is achieved after 4-6 weeks. The action persists with the continuation of the treatment; When discontinuing therapy, the cholesterol content gradually returns to the baseline level.

Pharmacokinetics:

Inside, the maximum concentration in the blood plasma is reached after about 1.3 - 2.4 hours, and decreases, by 90% after 12 hours. The connection with proteins - blood plasma is about 95%.

It enters the body in an inactive form. Hydrolyzed in tissues in its active form - beta-hydroxy acid and inactive metabolites. Metabolized in the liver, has the effect of "first passage" through the liver. In the metabolism of simvastatin, the isozymes CYP3A4, CYP3A5 and CYP3A7 are involved. The half-life of active metabolites is 1.9 hours. It is excreted mainly through, the intestine (60%) in the form of metabolites. About 10 -15% is excreted by the kidneys in an inactive form.

Indications:

- primary hypercholesterolemia (heterozygous familial and non-family, types IIa, IIIb, and mixed by Fredrickson classification) - with - poor diet low in cholesterol and other non-drug interventions (exercise and weight reduction) in patients with elevated. risk of developing coronary atherosclerosis;

- combined hypercholesterolemia and hypertriglyceridemia, hyperlipoproteinemia, which can not be corrected by special diet and exercise;

Cardiac ischemia:

secondary prevention to reduce the overall risk of death, myocardial infarction (to slow the progression of coronary atherosclerosis),

stroke and transient disorders of cerebral circulation ,. reducing the risk of revascularization procedures.

Contraindications:

Hypersensitivity to simvastatin or to other components of the drug, as well as to other drugs of the statin series (inhibitors of HMG-CoA reductase) in the anamnesis,
liver disease in the active phase, or persistent increase in the activity of "hepatic" transaminases of unclear etiology,
simultaneous administration of cytochrome P450 inhibitors of ZA4 (isoenzyme CYP3A4) (eg, itraconazole, ketoconazole, posaconazole, voriconazole, drugs containing a cobicystate, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin and nefazodone),
diseases of skeletal muscles (myopathy),
pregnancy and the period of breastfeeding,
age to 18 years (efficacy and safety of use not studied),
deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome,
concomitant treatment with gemfibrozil, cyclosporin or danazol

Carefully:alcoholism, liver disease in history, severe violations of water-electrolyte balance, expressed endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis),myopathy / acute necrosis of skeletal muscles, uncontrolled epilepsy, extensive surgical interventions, trauma; simultaneous reception with fibrates (except fenofibrate), nicotinic acid in lipid-lowering doses (more than 1 g / day), dronedarone, amiodarone, verapamil, diltiazem, grapefruit juice; severe renal failure (creatinine clearance less than 30 ml / min), advanced age (over 65 years, especially women), impaired renal function

Pregnancy and lactation:Simvastatin may have an unfavorable effect on the fetus and is contraindicated in pregnant women. There are several messages

on the development of anomalies in newborns whose mothers were taking simvastatin. Women of reproductive age who receive simvastatin, should, avoid conception. Application of the drug simvastatin is not recommended in women of childbearing age, not using reliable methods of contraception. If, in the course of treatment, the pregnancy did occur, simvastatin must be abolished, and a woman must be warned of a possible danger to the fetus.

Data on the isolation of simvastatin with breast milk are absent.

If it is necessary to use the drug simvastatin in the period of breastfeeding should 'take into account that many drugs are allocated.,

with breast milk and there is a threat of development of severe reactions, so breast-feeding while taking the drug should be discontinued.

Dosing and Administration:

Before the start of treatment with Simvastatin-SZ the patient should be prescribed a standard hypocholesterol diet, which should be observed throughout the course of treatment. Simvastatin-S3 should be taken orally 1 time per day in the evening, with plenty of water.

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

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

Hypercholesterolemia

The recommended dose of the drug Simvastatin-SZ for the treatment of hypercholesterolemia varies from 5 to 80 mg once a day in the evening.

If the drug is ineffective at a dose of 40 mg, it is recommended to switch to another type of lipid-lowering therapy. The use of the drug in a dose of more than 40 mg increases the significant risk of myopathy. The dose of Simvastatin-SZ 80 mg should be used only in those patients who did not achieve the target LDL concentration with a dose of 40 mg.

The recommended initial dose of the drug for patients with hypercholesterolemia is 10 mg. Changes (selection) of the dose should be carried out at intervals of 4 weeks. In most patients, the optimal effect is achieved when taking the drug at doses up to 20 mg per day.

In patients with homozygous hereditary hypercholesterolemia, the recommended daily dose of Simvastatin-SZ is 40 mg (2 tablets of 20 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). Such patients are recommended to use Simvastatin-SZ in combination with other lipid-lowering therapy (for example, apheresis of LDL).

Cardiac ischemia

In the treatment of patients with ischemic heart disease (CHD) or a high risk of developing coronary artery disease, with or without hyperlipidemia, effective doses of the drug Simvastatin-SZ 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 (2 tablets of 20 mg of the drug Simvastatin-SZ). 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.

Concomitant therapy

In patients treated with verapamil, diltiazem, fibrates (other than fenofibrate) or nicotinic acid in lipid-lowering doses (more than 1 g / day), or dronedarone, the recommended maximum daily dose of Simvastatin-SZ should not exceed 10 mg. Further increase in dose in such situations is not recommended.

For patients who simultaneously take amiodarone, amlodipine or ranolazine, the daily dose of Simvastatin-SZ should not exceed 20 mg.

In elderly patients and in patients with mild or moderately expressed renal insufficiency correction of the dose of the drug is not required.

In patients with severe renal insufficiency (creatinine clearance less than 30 ml / min) the recommended dose of the drug Simvastatin should not exceed 10 mg per day. When The need to increase the dose is carefully monitored for such patients.

Side effects:From the digestive system

Constipation pain in the abdomen, flatulence, indigestion, nausea, vomiting, diarrhea, pancreatitis, hepatitis, cholestatic jaundice, dysfunction of the liver. increased activity of "liver" transaminases, alkaline phosphatase, and creatine phosphokinase (CK).

From the central nervous system and sense organs

Asthenia, headache, paresthesia, dizziness, peripheral neuropathy, insomnia, memory impairment, muscle cramps, blurred vision, impaired taste sensations; myasthenia gravis, weakness. . '

From the musculoskeletal system:

Myopathy, rhabdomyolysis, myalgia, muscle cramps.

Allergic and immunopathological reactions-

. Deployed, hypersensitivity syndrome (angioedema, lupus-like syndrome, rheumatic polymyalgia, dermatomyositis, vasculitis, thrombocytopenia, eosinophilia, increased erythrocyte sedimentation rate (ESR), arthritis, arthralgia, urticaria, photosensitivity, fever, blood flushes to the skin of the face , shortness of breath).

Dermatological reactions

Skin rash, itching, alopecia.

Other '

Anemia, palpitations, acute renal failure (due to

rhabdomyolysis), decreased potency.

Overdose:In none of the known few cases of overdose (the maximum dose taken is 450 mg), no specific symptoms were identified.

Treatment is symptomatic, it is necessary to conduct general activities: monitoring and maintaining vital 'functions,prevention of further absorption of the drug (gastric lavage, intake of activated carbon or laxatives). It is necessary to monitor the liver and kidney function, the concentration of CFC. Serum, blood. ,

There is no specific antidote.

In the development of myopathy with rhabdomyolysis and acute renal insufficiency \ (a rare but severe side effect), the drug should be stopped immediately and the patient is administered [diuretic and sodium hydrobicarbonate (intravenous infusion).

Rhabdomyolysis can cause hyperkalemia, which can be eliminated by intravenous calcium or calcium gluconate injection, dextrose (glucose) infusion with short-acting insulin, the use of potassium ion exchange resins or, in severe cases, hemodialysis

Interaction:Fnormative forms of interaction Simultaneous use of simvastatin with fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day), dronedarone increases the risk of myopathy, including rhabdomyolysis (with simultaneous use with fenofranate, there is no evidence of an increased risk of myopathy compared with monotherapy with each drug alone).

The risk of myopathy / rhabdomyolysis increases with the simultaneous use of verapamil, diltiazem or amlodipine with simvastatin.

Simultaneous use of simvastatin with fusidic acid, with colchicine increases the risk of myopathy. With simultaneous therapy with these drugs, patients should be carefully monitored. Pharmacokinetic interactions Inhibitors of cytochrome isoenzyme CYP3A4 (itraconazole, ketoconazole, posaconazole, voriconazole, preparations containing a cobicystate, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors and nefazodone), involved in the metabolic conversion of simvastatin in the liver, increase the risk of myopathy and rhabdomyolysis during simvastatin therapy. Simultaneous use with these drugs is contraindicated. Caution should be given simultaneously with less potent inhibitors of isoenzyme CYP3A4: verapamil and daltiazem.

The daily dose of the preparation Simvastatin-SZ with simultaneous use with verapamil, dnlthiazem, dronedarone and fibrates (except fenofibrate) should not exceed 10 mg.

Simultaneous use with cyclosporine, dapazelom and gemfibroznl is contraindicated.

The daily dose of Simvastatin-SZ against the background of simultaneous application of amiodarop should not exceed 20 mg, unless the expected benefit is clearly not there is a potential risk of myopathy and rhabdomyolysis.

Simvastatin in a dose of 20-40 mg / day in healthy volunteers and patients with hypercholesterolemia potentiates the effects of indirect anticoagulants - coumarin derivatives (for example, warfarin), in particular the increase in progrombin time and the international normalized

relations (MI10). Therefore, in patients taking coumarin anticoagulants, irothrombinovos time and INR should be determined before the start of simvastatin therapy, in the initial treatment period, with a change in the dose of simvastatin or withdrawal of the drug. When a stable prothrombin time and INR are reached, further monitoring should be performed at intervals recommended for patients,

receiving therapy with anticoagulants. Therapy with simvastatin does not cause changes in prothrombin time and the risk of bleeding in patients who do not take anticoagulants. Kolestyramine and colstapol reduce bioavailability (application of the drug Simvastatin-SZ possible 4 hours after the application of these drugs, with an additive effect noted).

Simvastatin increases the concentration of digoxin in the blood plasma.

Grapefruit juice contains one or more components that inhibit the isoenzyme CYP3A4 and can increase the concentration of blood in the blood plasma 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 the use of the drug Simvastatin-SZ significantly increases the 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:FROMConcurrent therapy with strong isoenzyme inhibitors CYP3A4 in therapeutic doses (for example, itraconazol, ketoconazole, posaconazole, voriconazole, preparations containing a co-bicystate, boceprevirov, telaprevir, erythromycin, clarithromycin,telithromycin, HIV protease inhibitors and psephazodone) increases the risk of myopathy and rhabdomyolysis. The simultaneous use of the drug Simvastatin-SZ with these drugs is contraindicated. Simultaneous use with cyclosporine, dapazelom and gemfibrozilom contraindicated.

At the beginning of therapy with Simvastatin-SZ, a transient increase in the activity of "hepatic" enzymes is possible.

Before starting therapy, continue to conduct regular liver function tests (monitor the activity of liver enzymes 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 also with increasing doses, test for the determination of liver function. When the dose is raised to 80 mg, a test should be performed every 3 months. With a persistent increase in the activity of transaminases (3-fold compared with baseline), the preparation of Simvastatin-SZ should be discontinued.

Simvastatin-SZ preparation, like 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).

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 patients with reduced thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome) with an increase inAt the center of cholesterol, the underlying underlying disease should first be treated.

Preparation Simvastatin-SZ 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 hypoholesterin diet.

Simultaneous reception of grapefruit juice can increase the severity of side effects associated with taking the drug Simvastatin-SZ, so you should avoid their simultaneous reception.

The drug Simvastatin-SZ is not indicated in cases where there is hypertriglyceridemia 1, IV and V types.

Treatment with the drug Simvastatin-SZ can cause myopathy, leading to rhabdomyolysis and kidney failure. The risk of this pathology increases in patients receiving simultaneously with the preparation Simvastatin-SZ one or more of the following drugs: fibrates (fenofibrate), dronedaron, macrolides.The risk of developing mionatation is also increased in patients with severe renal failure.

Among the predisposing factors for the development of mionatia are the elderly (over 65 years), females, uncontrolled hypothyroidism and renal insufficiency.

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

In order to diagnose the development of mIopathy is recommended regularly

measure activity

creatine phosphokinase (CKF).

When treated with Simvastatin-SZ

possibly increased activity

serum 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 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 CPK, drug treatment is discontinued.

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 time for the next dose, do not double the dose.

Patients with severe renal failure receive iodine for renal function.

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

The use of the drug is not recommended in women of childbearing age who do not use reliable methods contraception.

Effect on the ability to drive transp. cf. and fur:Care must be taken when driving vehicles and various mechanisms (development of dizziness)

Form release / dosage:

Tablets, film-coated, 10 mg, 20 mg and 40 mg.

For 10 or 14 tablets in a contour mesh package.

For 20, 28, 30, 60, 84 or 90 tablets in a can of polymer or a polymer bottle.

Each jar or bottle or 2, 3, 6, 9 contour cell packs of 10 Tablets or 1, 2, 3, 4, 5, 6 contour cell packs of 14 tablets together with the instructions for use are placed in a pack of cardboard.

Packaging:

For 10 or 14 tablets in a contour mesh package.

For 20, 28, 30, 60, 84 or 90 tablets in a can of polymer or a polymer bottle.

Each jar or bottle or 2, 3, 6, 9 contour cell packs of 10 Tablets or 1, 2, 3, 4, 5, 6 contour cell packs of 14 tablets together with the instructions for use are placed in a pack of cardboard.

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

Keep out of the reach of children.

Shelf life:3 years.

Do not use, at the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000667

Date of registration:28.09.2011

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Information update date: & nbsp02.02.2015

Illustrated instructions

Instructions

Simvastatin-SZ (Simvastatin-SZ)