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

Dosage 10 mg. Active substance (mg): simvastatin 10.00; auxiliary substances (mg): ascorbic acid 2.50, butyl hydroxy anisole 0.02, citric acid (monohydrate) 1.25, microcrystalline cellulose 5.00, starch corn pregelatinized starch 10.00, magnesium stearate 1.70, lactose monohydrate to 100.00; sheath - opadrai pink OY-B-34915 3,00.

Dosage 20 mg. Active substance (mg): simvastatin 20.00; auxiliary substances (mg): ascorbic acid 5.00, butylhydroxyanisole 0.04, citric acid (monohydrate) 2.50, microcrystalline cellulose 10.00,starch corn pregelatinized 20.00, magnesium stearate 3.40, lactose monohydrate to 200.00; sheath - opadrai pink OY-B-34917 6,00.

Dosage 40 mg. Active substance (mg): simvastatin 40.00; auxiliary substances (mg): ascorbic acid 10.00, butyl hydroxy anisole 0.08, citric acid (monohydrate) 5.00, microcrystalline cellulose 20.00, corn pregelatinized corn starch 40.00, magnesium stearate 6.80, lactose monohydrate to 400.00; shell - opadraj brown АМВ 80W36564 12,00.

The composition of all film shells includes the following components: polyvinyl alcohol, titanium dioxide E 171, talc, lecithin, xanthan gum E 415, iron dye red oxide E 172, iron dye oxide yellow E 172; sheath Opadrai pink OY-B-34915 contains in addition in the dye composition indigocarmine aluminum lacquer E 132; shells Opadrai pink OY-B-34917 and Opadrai brown AMB 80W36564 contain additionally as part of the iron dye oxide black E172.

Description:

Dosage 10 mg: round biconvex tablets, covered with a film coat of light pink color.

Dosage of 20 mg: round biconvex tablets, covered with a film shell of pink color, with a risk on one side.

Dosage of 40 mg: Round biconvex tablets, film-coated dark pink color with the notch on one side.

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 undergoes hydrolysis with the formation of a hydroxy-acid derivative. The active metabolite inhibits the H-W-hydroxy-methyl-glutaryl-CoA reductase (HMG-CoA reductase), an enzyme that catalyzes the initial reaction of mevalonate formation of 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.

Simvastatin causes a decrease in blood plasma triglycerides (TG), low density lipoprotein (LDL), very low density lipoproteins (VLDL) and total cholesterol (in cases of heterozygous familial hypercholesterolemia and non-familial forms, mixed with hyperlipidemia).

Increases the high-density lipoprotein (HDL) content and reduces the ratio of LDL / HDL and total cholesterol / HDL.

Therapeutic effect first appears in 2 weeks after the start of regular intake of simvastatin, the maximum effect is achieved in 4-6 weeks. The action of simvastatin persists throughout the treatment period, after the withdrawal of simvastatin, the cholesterol content gradually returns to its original value.

Pharmacokinetics:

Suction. Simvastatin is absorbed in the gastrointestinal tract (GIT) by 85% regardless of food intake. The maximum concentration in the blood plasma is reached after approximately 1.3-2.4 hours and decreases by 90% after 12 hours.

Distribution. The connection with plasma proteins is about 95%.

Metabolism. At primary passage through the liver is metabolized in a significant amount with the formation of beta-hydroxy acid, as well as 4 active and other inactive metabolites with the help of isoenzyme CYP3A4 cytochrome P450.

The metabolic rate depends on the blood flow in the portal portal vein system. The bioavailability of simvastatin is less than 5%. The metabolism of simvastatin in the blood is extremely slow. With multiple reception simvastatin does not accumulate in the body.

Excretion. The half-life of active metabolites is 1.9 hours. Simvastatin is excreted mainly through the intestine (60%) in the form of metabolites. About 10-15% of the injected simvastatin is excreted by the kidneys unchanged.

Indications:

Hypercholesterolemia

Primary hypercholesterolemia (type Pa and Pb according to Fredrickson classification) as a supplement to diet therapy and other non-medicamental methods of treatment (for example, physical activity increase, body weight correction) when these methods of treatment are not effective enough.
Combined hypercholesterolemia, hypertriglyceridemia,

hyperlipoproteinemia, which can not be corrected by a special diet and increased physical activity.

Homozygous hereditary hypercholesterolemia as a supplement to diet therapy and other lipid-lowering therapy (including LDL-apheresis), when these methods of treatment are not effective enough.

Ischemic heart disease

Reducing the risk of overall mortality by reducing mortality due to coronary heart disease (CHD).
Reducing the risk of serious vascular and coronary events:

non-fatal myocardial infarction,

coronary death,

stroke,

revascularization operations.

Reducing the risk of the need for coronary blood flow restoration (such as aorto-coronary bypass and percutaneous transluminal coronary angioplasty).
Reducing the risk of the need for surgical intervention to restore peripheral blood flow and other types of non-coronary revascularization.

Contraindications:

Hypersensitivity to simvastatin or other components of the drug; hypersensitivity reactions to other drugs of the statical series (HMG-CoA-reductase inhibitors) in the anamnesis; diseases of skeletal muscles (myopathy); liver disease in the active stage or an increase in the activity of "hepatic" transaminases in the serum of unclear etiology; lactose intolerance, lactase deficiency or glucose-galactose malabsorption; pregnancy; lactation period; simultaneous use of inhibitors CYP3A4 (ketoconazole, itraconazole, HIV protease inhibitors, erythromycin, clarithromycin, telithromycin, nefazodone); severe acute infectious diseases; marked decrease in blood pressure; planned surgicaloperation; injury; severe metabolic disorders, age under 18 years (efficacy and safety not established).

Carefully:

In the presence of risk factors for myopathy / rhabdomyolysis (age over 65, when used in women, uncontrolled hypothyroidism, muscle disease in the family history, renal dysfunction, especially with creatinine clearance less than 30 mL / min, myopathies / rhabdomyolysis associated with with the use of statins and fibrates in the anamnesis, alcoholism); when used simultaneously with cyclosporine, danazol, gemfibrozil, other fibrates (with the exception of fenofibrate) or lipid-lowering doses (at least 1 g / day) of nicotinic acid, amiodarone, verapamil, diltiazem, grapefruit juice, fusidic acid; patients after organ transplantation who undergo immunosuppressant therapy (due to an increased risk of rhabdomyolysis and renal insufficiency); 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,disturbances of electrolyte balance, surgical interventions (including dental), or trauma; patients with decreased or increased tone of skeletal muscles of unknown etiology; epilepsy.

Pregnancy and lactation:

Symmal is contraindicated during pregnancy. There are cases of congenital anomalies in children whose mothers have been taking simvastatin during pregnancy. The development of such anomalies is associated with the inhibition of mevalonate synthesis in the fetus.

Women of childbearing age who receive simvastatin, should use reliable methods of contraception. If in the process of treatment the pregnancy nevertheless has come or is suspected of it, the preparation of Simcal should be immediately canceled. The abolition of lipid-lowering drugs during pregnancy does not have a significant effect on the results of long-term treatment of primary hypercholesterolemia.

Data on the isolation of simvastatin and its metabolites with breast milk are absent. In connection with the possibility of developing serious adverse events in children whose mothers take Simcal during lactation,if necessary, breastfeeding should be discontinued.

Dosing and Administration:

Inside, once a day in the evening, with plenty of water. The recommended dose varies from 5 to 80 mg per day. If necessary, the dose should be changed at least 4 weeks apart. A dose of 80 mg / day is recommended for use only in patients who did not achieve the desired result in the concentration of LDL when taking a dose of 40 mg and patients taking diltiazem simultaneously with the preparation Simgal. The daily dose should not exceed 40 mg. Hypercholesterolemia. Before treatment, the patient is given a diet with a hypo cholesterol diet. Dietotherapy should be continued during treatment with Simcal, the initial dose is 10-20 mg per day.

If you want to reduce the concentration of LDL in the blood by 45% or more, the initial dose may be 20-40 mg / day.

If necessary, the dosage can be changed.

In patients with homozygous hereditary hypercholesterolemia, the recommended dose is 40 mg / day once or 80 mg / day, divided into 3 doses (20 mg in the morning, 20 mg in the afternoon and 40 mg in the evening).The preparation of Simcal is adopted in addition to diet therapy and other lipid-lowering therapy or if they are ineffective.

Cardiac ischemia. The initial dose is 20 mg 1 time in the evening, if necessary, the dose is gradually increased every 4 weeks. up to 40 mg.

If the LDL is not less than 75 mg / dl (1.94 mmol / l) and the total cholesterol is less than 140 mg / dL (3.6 mmol / L), the dose should be reduced. Therapy with Simgal is applied simultaneously with diet therapy and increased physical activity. If necessary, the dose should be changed.

Combination therapy with other drugs

Combination with cyclosporine, danazol, gemfibrozil, other fibrates (with the exception of fenofibrate) or lipid-lowering doses (at least 1 g / day) of nicotinic acid

The dose of Simcal should not exceed 10 mg / day.

Combination with amiodarone or verapam

The dose of Simcal should not exceed 20 mg / day.

Combination with bile acid sequestrants

Simcal should be taken 2 hours before or 4 hours after taking bile acid sequestrants.

Renal failure. Correction of the dose with mild and moderate renal failure is not required.In severe renal failure (QC less than 30 ml / min) daily dose should not exceed 10 mg / day. It is necessary to carry out treatment under the supervision of a doctor.

Elderly age. Correction of the dose is not required.

Side effects:

The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01% (including isolated cases).

From the hemopoietic system and lymphatic system: rarely - anemia.

From the nervous system: very often insomnia; rarely - headache, dizziness, paresthesia, peripheral neuropathy; very rarely - memory impairment, sleep disturbance, nightmares, depression.

From the digestive tract: rarely - abdominal pain, constipation, flatulence, nausea, diarrhea, vomiting, acute pancreatitis,

From the liver and bile ducts: rarely - jaundice, hepatitis; very rarely liver failure.

From the respiratory system, chest organs of the mediastinum: very rarely - interstitial lung disease (with long-term treatment).

From the skin: rarely - alopecia.

Allergic reactions: rare - skin rash, skin itch, urticaria, hypersensitivity syndrome (angioedema, lupus-like syndrome, rheumatic polymyalgia, vasculitis, thrombocytopenia, eosinophilia, increased erythrocyte sedimentation rate, arthritis, arthralgia, photosensitivity, fever, skin hyperemia, blood flushes to the skin face, shortness of breath, feeling of indisposition).

From the musculoskeletal system: rarely - myopathy, myalgia, muscle cramps, rhabdomyolysis.

Laboratory indicators: rarely - increased activity of "hepatic" transaminases (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase), alkaline phosphatase, CKK in serum.

Other: rarely - asthenia, palpitations, acute renal failure (due to rhabdomyolysis), a decrease in potency.

Overdose:

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

Treatment: induction of vomiting, reception of activated charcoal, symptomatic therapy. It is necessary to monitor the liver and kidney function, the activity of CKK in the blood serum.With the development of myopathy / rhabdomyolysis and acute renal failure (a rare but severe side effect), immediately stop taking Simcal and inject the patient with a diuretic and a solution of sodium bicarbonate (intravenous (IV) infusion). If necessary, hemodialysis is indicated.

Rhabdomyolysis can cause hyperkalemia, which can be eliminated by / in the administration of calcium chloride or calcium gluconate, infusion of a 5% dextrose solution with short-acting insulin, the use of potassium ion exchangers or, in severe cases, hemodialysis.

Interaction:

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

Ciclosporin shea danazol: the risk of myopathy / rhabdomyolysis increases with simultaneous use of cyclosporine or danazol with high doses of simvastatin.

Other hypolipidemic agents that can cause the development of myopathy: the risk of myopathy increases with simultaneous use of other lipid-lowering drugs,which are not potent inhibitors of the isoenzyme CYP3A4, but can cause myopathy with monotherapy. These include gemfibrozil and other fibrates (except fenofibrate), and a nicotinic acid in a lipid-lowering dose of not less than 1 g per day.

Amiodaron and verapamsh: the risk of myopathy increases with simultaneous use of amiodarone or verapamil with high doses of simvastatin.

Amlodipine and dthiazium: The risk of myopathy is slightly increased in patients receiving amlodipine or diltiazem simultaneously with simvastatinom in a dose of 80 mg.

Simvastatin potentiates the action indirect anticoagulants (for example, fenprokumone, warfarin) and increases the risk of bleeding, which requires

monitoring of blood clotting rates before the start of treatment, and also often enough in the initial period of therapy. Once a stable level of prothrombin time or an international normalized ratio (INR) is reached, its further control should be performed at intervals recommended for patients receiving indirect anticoagulant therapy.When changing the dose or stopping the intake of simvastatin, it should also be monitored prothrombin time or INR in the above scheme.

Therapy with simvastatin does not cause changes in prothrombin time and the risk of bleeding in patients not taking indirect anticoagulants.

Increases concentration digoxin in the blood plasma.

Kolestyramine and colestipol reduce the bioavailability (the use of simvastatin is possible 4 hours after the administration of these drugs, with an additive effect noted).

Grapefruit juice contains one or more components that inhibit the isoenzyme CYP3A4 and can increase the concentration of blood in the blood plasma metabolized with the participation of isoenzyme CYP3A4. An 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, the consumption of a large amount of juice (more than 1 liter per day) with the administration of simvastatin 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:

Simcal, like other inhibitors of HMG-CoA reductase, in rare cases can cause myopathy, accompanied by muscle pain, muscle weakness, the activity of CK in the blood plasma is 10 times higher than the upper limit of the norm (VGN). Sometimes myopathy occurs in the form of rhabdomyolysis with acute renal failure due to myoglobinuria or without renal failure; very rarely with a fatal outcome. The risk of developing myopathy / rhabdomyolysis increases with an increase in the concentration of simvastatin in the blood. An increase in the activity of CK may indicate myopathy only if the patient had no physical activity before the study and other factors that could cause an increase in CK activity were excluded. If before the treatment with Symmal the activity of CK is 5 times higher than VGN, it is necessary to repeat the test after 5-7 days to confirm the results.

In order to diagnose myopathy during treatment, the activity of CK in the blood should be regularly determined. When the activity of CK is 5 times higher than IGN, when diagnosing myopathy or suspicion of it, Symmal is stopped.

All patients starting therapy with Simgal, as well as patients who need to increase the dose of Simgal, 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 or muscle weakness, especially if this is accompanied by a malaise or fever.

In the presence of risk factors for myopathy / rhabdomyolysis such as age over 65, when used in women, uncontrolled hypothyroidism, muscle history in the family history, impaired renal function, especially with QC less than 30 mL / min, myopathy / rhabdomyolysis associated with the use of statins and fibrates in anamnesis, alcoholism, the use of simvastatin is possible only if the expected benefit exceeds the possible risk.

In case prior to treatment with Symgal, the activity of CK is 5-fold higher than IGN in patients with myopathy / rhabdomyolysis associated with the use of statins and fibrates, treatment with Simcal should not begin.

If muscle pain, weakness, or seizures appear during treatment with Simgal,it is necessary to determine the activity of CK. When the activity of CK is 5 times higher than ULN, treatment with Simgal should be stopped. Provided that after the withdrawal of the Simgal drug, the activity of CK decreased to ULN, it is possible to continue treatment with Simcal at a lower dose with careful monitoring of the activity of CKK.

When using Simcal in a daily dose of 80 mg / day, the risk of myopathy significantly increases. Regular examination of the activity of CK in this mode of administration can help to identify cases of subclinical myopathy. However, there is no guarantee that such monitoring of the activity of CKK will prevent the development of myopathy.

Treatment with Symmal should be stopped several days before the planned surgical operation (including dental), and also should not be performed in the post-operation period.

At the beginning of therapy with the preparation of Simcal, a transient moderate increase in the activity of "hepatic" transaminases (less than 3 times as compared with ULN) is possible, which is usually not accompanied by any pathological symptoms and does not require discontinuation of therapy.

Before and during therapy, it is recommended that liver function tests be performed regularly (to 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) The liver should also be administered with an increase in the dose of Simcal. With an increase in the daily dose to 80 mg / day, this test should be carried out every 3 months. With a stable increasewThe activity of "hepatic" transaminases (more than 3 times as compared with VGN) should be stopped.

Simcal should be used with caution in patients who consume a significant amount of alcohol.

Single reports were received about cases of development of interstitial lung disease associated with long-term therapy with simvastatin, which was manifested by shortness of breath, cough with sputum, deterioration in general condition (fatigue, weight loss, fever). With the development of such conditions, therapy with Simgal should be stopped.

Simcal, like other inhibitors of HMG-Co-A-reductase,should not be used against the background of severe acute infectious diseases, arterial hypotension, trauma, severe metabolic disorders.

In patients with reduced thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome) with increasing cholesterol concentration, first therapy of the underlying disease should be performed.

Before and during treatment with Simgal, the patient should be on a hypocholesterol diet.

Simvastatin is not indicated in hypertriglyceridemia I, IV and V type.

If the current dose is skipped, the drug should be taken as soon as possible. If it's time to take the 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:

Care should be taken when managing transport and other mechanisms due to the fact that the preparation of Simcal can cause unwanted reactions (dizziness, etc.) that affect the speed of psychomotor reactions and concentration of attention.

Form release / dosage:

Tablets, film-coated

For 7 tablets in a blister of PVC / A1. 1 blister is placed in a cardboard box together with instructions for use. For 14 tablets in a blister of PVC / A1, 1, 2 or 6 blisters are placed in a cardboard box together with instructions for use.

Packaging:For 7 tablets in a blister of PVC / A1. 1 blister is placed in a cardboard box together with instructions for use. For 14 tablets in a blister of PVC / A1, 1, 2 or 6 blisters are placed in a cardboard box together with instructions for use.

Storage conditions:

In the dark place at a temperature of 10 to 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years. Do not use at the end of the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012856 / 01

Date of registration:03.10.2011

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Czech Industries, s.r.o. Czech Republic

Representation: & nbspTeva Teva Israel

Information update date: & nbsp03.10.2011

Illustrated instructions

Instructions

Simgal (Simgal)