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

Excipients: lactose 70.726 mg, corn starch 10.0 mg, microcrystalline cellulose 5.0 mg, butyl hydroxy anisole 0.024 mg, ascorbic acid 2.5 mg, citric acid 1.25 mg, magnesium stearate 0.5 mg, hydroxypropylmethyl cellulose 0.764 mg; hydroxypropyl cellulose 0.764 mg; titanium dioxide (E171) 0.694 mg; talc 0.2277 mg, iron dye oxide yellow (E 172) 0.0015 mg, iron dye red oxide (E 172) 0.0038 mg.

1 tablet coated with a film coating of 20 mg contains:

Active substance: simvastatin 20 mg

Excipients: lactose 141.452 mg, corn starch 20.0 mg, microcrystalline cellulose 10.0 mg, butyl hydroxy anisole 0.048 mg, ascorbic acid 5.0 mg, citric acid 2.5 mg, magnesium stearate 1.0 mg, hydroxypropylmethyl cellulose 1.527 mg; hydroxypropyl cellulose 1.527 mg; titanium dioxide (E171) 1.388 mg; talc 0.536 mg, iron oxide dye yellow (E 172) 0.022 mg.

1 tablet coated with a film jacket of 40 mg contains:

Active substance: simvastatin 40 mg

Excipients: lactose 282,904 mg, corn starch 40.0 mg, microcrystalline cellulose 20.0 mg, butyl hydroxy anisole 0.096 mg, ascorbic acid 10.0 mg, citric acid 5.0 mg, magnesium stearate 2.0 mg, hydroxypropylmethyl cellulose 3 , 05 mg .; hydroxypropyl cellulose 3.05 mg; titanium dioxide (E171) 2.78 mg; talc 1.0 mg, iron oxide red (E 172) 0.12 mg.

Description:

Simvastatin - Chaikafarma tablets, coated with 10 mg capsules: oval tablets covered with a peach-colored coating, with a risk on one side; Simvastatin - Chaykafarma tablets, coated with 20 mg: oval tablets, coated with a yellow coating, with a risk on one side; Simvastatin - Chaykafarma tablets coated with 40 mg: round, flat-cylindrical tablets, covered with a dark pink 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 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 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.

Simvastatin causes a decrease in plasma concentrations of triglycerides (TG), low-density lipoproteins (LDL), and very low-density lipoproteins (VLDL) and total cholesterol (in cases of heterozygous familial and non-familial forms of hypercholesterolemia,with mixed hyperlipidemia, when an increased concentration of cholesterol is a risk factor for the development of cardiovascular diseases).

Increases the concentration of high density lipoproteins (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 concentration of cholesterol gradually returns to the initial value.

Pharmacokinetics:

Suction: after ingestion simvastatin absorbed from the gastrointestinal tract (GIT) - about 61-85% and enters the systemic circulation. The maximum therapeutic concentration in the blood plasma is achieved in 1.3 - 2.4 hours and decreases by 90% after 12 hours. Simultaneous food intake does not affect the absorption of simvastatin.

Distribution: the association with plasma proteins is about 98%. Metabolism: simvastatin is subjected to the effect of "primary transmission" through the liver (mainly hydrolysed to its active form beta-hydroxy acid). In the metabolism of the drug, isozymes CYP3A4, CYP3A5 and CYP3A7 are involved.The half-life of active metabolites is 1.9 hours. The concentration of the active metabolite of simvastatin in the systemic circulation is 5% of the dose.

Excretion: the half-life of active metabolites is 1.9 hours. It is excreted mainly through the intestine (about 60%) in the form of metabolites. About 10-15% is excreted by the kidneys in an inactive form.

The possibility of the penetration of simvastatin through the blood-brain barrier and the hematoplacental barrier has not been studied.

Indications:

- Primary hypercholesterolemia (type Pa and IL according to Fredrickson) with ineffectiveness of diet therapy with low cholesterol and other non-medicamentous measures (physical activity and weight loss in patients with an increased risk of coronary atherosclerosis);
combined hypercholesterolemia and hypertriglyceridemia; hyperlipoproteinemia, which can not be corrected by a special diet and exercise;
homozygous hereditary hypercholesterolemia (as an adjunct to hypolipidemic therapy);
ischemic heart disease (secondary prevention): the drug is indicated to patients in order to reduce the overall mortality; with the aim ofreducing the risk of coronary mortality and preventing myocardial infarction; with the aim of reducing the risk of stroke and transient cerebral circulatory disorders; with the purpose of slowing the progression of coronary atherosclerosis

Contraindications:

hypersensitivity to simvastatin or to other components of the drug, as well as 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,
diseases of skeletal muscles (myopathy),
age under 18 years (safety and efficacy not established);
deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome.
simultaneous application with potent inhibitors of the isoenzyme CYP3A4 (itraconazole, ketoconazole, pozakonzal, inhibitors of HIV protease, erythromycin, clarithromycin, telithromycin and nefazodone);
simultaneous application with gemfibrozole, cyclosporin or danazol.
With caution: patients with alcoholism, liver disease in anamnesis, 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 function deficiency, such as arterial hypotension, acute infectious diseases of severe course, severe metabolic and endocrine disorders, violations of the electro-electrolyte balance, surgical interventions (including dental), or trauma; patients with decreased or increased tone of skeletal muscles of unknown etiology; epilepsy, uncontrolled convulsions; simultaneous reception with fibrates (except gemfibrozil), nicotinic acid in lipid-lowering doses (more than 1 g / day), amiodarone, verapamil, diltiazem, grapefruit juice; marked renal failure (creatinine clearance less than 30 ml / min).

Pregnancy and lactation:

Simvastatin-Chaikafarma is contraindicated and should not be given to pregnant women, as well as to women who are pregnant or planned.

Since safety for pregnant women is not proven and there is no data,that treatment with Simvastatin-Chaikafarm during pregnancy will be of greater benefit than risk for the fetus, the drug should be stopped immediately when diagnosing pregnancy. If during pregnancy Simvastatinom-Chaikafarma is diagnosed as pregnant, the drug should be canceled, and the woman herself is warned about possible danger to the fetus (see contraindications section).

There are no data on the isolation of simvastatin in breast milk, but since a small amount of other drugs of this class is excreted in breast milk, women taking simvastatin-Chaikafarma are not recommended breast-feeding because of the possibility of developing serious unwanted reactions in children.

Dosing and Administration:

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

Simvastatin-Chaikafarma is taken orally once a day in the evening, with plenty of water. The time of taking the drug should not be associated with eating.

Recommended doses for the treatment of hypercholesterolemia are from 5 to 80 mg, should be taken once a day in the evening.When choosing a dose of Simvastatin-Chaikafarm, its change should be made at intervals of not less than 4 weeks. The recommended initial dose for patients with severe hypercholesterolemia is 10 mg. In most patients, the optimal effect is achieved when taking the drug at a dose of 20 mg per day. The maximum daily dose is 80 mg.

A dose of 80 mg should be given only to patients who did not achieve the desired LDL result with a dose of 40 mg.

In patients with homozygous hereditary hypercholesterolemia, the recommended daily dose 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). A dose of 80 mg is recommended to be administered only if the intended benefit of therapy exceeds the possible risk.

In the treatment of patients with ischemic heart disease (CHD) or a high risk of CHD, an initial dose of 20 mg per day in the evening; if necessary, the dose is gradually increased every 4 weeks to 40 mg.

In elderly patients and in patients with mild or moderate degree of renal insufficiency, dose changes are not required.

In patients with chronic renal insufficiency (creatinine clearance less than 30 ml / min) or fibrates (except fenofibrate and gemfibrozil), nicotinic acid in lipid-lowering doses (> 1 g / day) in combination with Simvastatin-Chaikafarm, the maximum recommended dose of Simvastatin-Chaikafarm should not exceed 10 mg per day. For patients receiving amiodarone or verapamil Simvastatin-Chaikafarm, the daily dose should not exceed 20 mg, and for patients taking diltiazem Simvastatin-Chaikafarm, the daily dose of Simvastatin-Chaikafarm should not exceed 40 mg.

Side effects:

From the digestive system: dyspepsia (nausea, vomiting, gastralgia, abdominal pain, constipation or diarrhea, flatulence), hepatitis, cholestatic jaundice, impaired liver function, increased activity of "liver" transaminases, alkaline phosphatase and creatine phosphokinase (CKF); acute pancreatitis.

From the side of the central nervous system and sensory organs: asthenia, dizziness, headache, memory impairment, insomnia, paresthesia, peripheral neuropathy, indistinct perception, violation of taste sensations.

From the musculoskeletal system: myopathy, myalgia, myasthenia gravis; rhabdomyolysis.

Allergic reactions: skin rash, itching, urticaria, alopecia,

angioneurotic edema, lupus-like syndrome, rheumatic polymyalgia, vasculitis, thrombocytopenia, eosinophilia, increased erythrocyte sedimentation rate (ESR), arthritis, arthralgia, photosensitivity, fever, skin hyperemia, blood flushes to the skin of the face, dyspnea.

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 activity of CKK in the blood serum.

With the development of myopathy with rhabdomyolysis and acute renal failure (a rare but severe side effect), stop taking the drug immediately and inject the patient with a diuretic and a solution of sodium bicarbonate (intravenous infusion). If necessary, hemodialysis is indicated.

Rhabdomyolysis can cause hyperkalemia, which can be eliminated by intravenous calcium chloride or calcium gluconate, by infusing 5% dextrose (glucose) solution with short-acting insulin.

Interaction:

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

When combined use of cyclosporine or danazol increases the risk of myopathy / rhabdomyolysis.

With the simultaneous use of amlodipine with simvastatin in a dose of 80 mg, there is an insignificantly increased risk of myopathy.

Increased risk of myopathy concomitant use of other lipid-lowering drugs that are not potent inhibitors of the CYP3A4 isoenzyme, but capable of causing myopathy under monotherapy. Such as gemfibrozil and other fibrates (except fenofibrate), as well as a nicotinic acid in lipid-lowering doses (more than 1 g per day).

The risk of developing myopathy increases with simultaneous use of amiodarone or verapamil withhigh doses of simvastatin.

The risk of myopathy is slightly increased in patients receiving diltiazem simultaneously with simvastatinom in a dose of 80 mg.

Simvastatin potentiates the effect of indirect anticoagulants (for example, fenprokumone, warfarin) and increases the risk of bleeding, which requires the need to monitor the coagulability of the blood before the treatment, and often enough in the initial period of therapy. Once a stable level of prothrombin time or an International Normalized Ratio (INR) is reached, further monitoring 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. Simvastatin increases the concentration of digoxin in the blood plasma.

Kolestyramin and colestipol reduce bioavailability (the use of simvastatin-Chaikafarm is possible 4 hours after taking these medications, with an additive effect noted).

Grapefruit juice contains one or more components that inhibit the CYP3A4 isoenzyme and can increase the concentration in the blood plasma of agents metabolized with the participation of the CYP3A4 isoenzyme. 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 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.

With the simultaneous use of simvastatin with fusidic acid, the risk of myopathy increases.

With the simultaneous use of colchicine and simvastatin in patients with impaired renal function, cases of myopathy and rhabdomyolysis are described (monitoring of patients' condition is necessary).

Special instructions:

At the beginning of Simvastatin-Chaikafarm therapy, a transient increase in the activity of "liver" transaminases is possible.

Simvastatin-Chaikafarma is effective both in monotherapy and in combination with bile acid sequestrants.

Before and during the course of treatment, the patient should be on a hypocholesterol diet.

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. The duration of the drug is determined by the doctor individually.

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 also with increasing doses, test for the determination of liver function.

Patients receiving Simvastatin-Chaikafarm in a daily dose of 80 mg, liver function is monitored once in 3 months. In those cases when the activity of "hepatic" transaminases increases (exceeding the upper limit of the norm by 3 times), therapy is canceled.

In patients with myalgia, myasthenia gravis and / or with a marked increase in the activity of CKK, treatment with the drug is stopped.

Among the predisposing factors for the development of myopathy, there are elderly age (over 65 years), belonging to the female sex, uncontrolled hypothyroidism and renal insufficiency.

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.

Simvastatin-Chaikafarma, like other inhibitors of HMG-CoA reductase, should not be used at an increased risk of rhabdomyolysis and renal insufficiency (due to severe acute infection, arterial hypotension, planned large surgery, trauma, severe metabolic disorders).

All patients starting therapy with Simvastatin-Chaikafarm, 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, or myasthenia gravis, 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.

When treatment with the drug Simvastatin-Chaikafarma may increase the activity - CKK in the serum, 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 CKC, the drug is stopped on the background of treatment.

The risk of myopathy and rhabdomyolysis increases significantly with the simultaneous use of simvastatin and potent inhibitors of the isoenzyme CYP3 A4 (for example, itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone) (see "Interactions with Other Drugs" Contraindications "), which indicates

0 contraindication of their joint application.

The risk of myopathy and rhabdomyolysis also increases with the combined use of fibrates, cyclosporine and nicotinic acid in lipid-lowering doses (more

1 g / day), as well as amiodarone and verapamil with high doses of Simvastatin-Chaikafarm (above 20 mg / day). In patients who received diltiazem Simvastatin-Chaikafarma in a dose of 80 mg, the risk of myopathy increased.

The use of the drug Simvastatin-Chaikafarm is not recommended in women of childbearing age who do not use reliable contraceptives.

The abolition of lipid-lowering drugs during pregnancy does not have a significant effect on the results of long-term treatment of primary hypercholesterolemia.

Simultaneous reception of grapefruit juice can increase the severity of side effects associated with taking the drug, therefore, simultaneous reception should be avoided.

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

Influence on ability to drive vehicles and employment by other kinds of activity demanding the raised concentration of attention and speed of psychomotor reactions

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

The adverse effect of the drug on the ability to drive vehicles and engage in other activities that require concentration and speed of psychomotor reactions were not reported. However, given that the drug can cause dizziness, blurred vision, you should be careful when implementing these activities.

Form release / dosage:

The tablets are covered with a film membrane of 10,20 and 40 mg.

10 tablets per blister. For 3 blisters together with instructions for use in a pack of cardboard.

Packaging:10 tablets per blister. For 3 blisters together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C in a dry and dark place.

Keep out of the reach of children!

Shelf life:

3 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000677

Date of registration:28.09.2011

The owner of the registration certificate:Chaikafarma High-quality Medicines, AO Chaikafarma High-quality Medicines, AO Bulgaria

Manufacturer: & nbsp

Chaikafarma High-quality Medicines, AO Bulgaria

Information update date: & nbsp28.09.2011

Illustrated instructions

Instructions

Simvastatin-Chaikafarma (Simvastatin-Tchaikapharma)