Zocor coated pills 20mg N28
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Active ingredients
Simvastatin
Release form
Pills
Composition
Simvastatin 20 mg additives: butylhydroxyanisol, ascorbic acid, lactose monohydrate, citric acid, pregelatinized starch, microcrystalline cellulose, magnesium stearate.
Pharmacological effect
After ingestion, simvastatin, which is an inactive lactone, undergoes hydrolysis in the liver to form an active beta-hydroxy-acid derivative, which is the main metabolite and has a high inhibitory activity against HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase enzyme, catalyzes the initial and most significant stage of cholesterol biosynthesis. Clinical studies have demonstrated the effectiveness of Zocor in reducing total cholesterol in blood plasma (X), low density lipoprotein (LDL), triglyceride (TG) and very low density lipoprotein (VLDL), as well as increasing high-density lipoprotein (HDL) in patients with heterozygous familial and nonfamily forms of hypercholesterolemia, as well as mixed hyperlipidemia in cases where elevated cholesterol is a risk factor and dietary alone is not enough. A noticeable therapeutic effect was achieved within 2 weeks of taking the drug, the maximum therapeutic effect - 4-6 weeks after the start of treatment. The effect persists with continued treatment. When discontinuing therapy with simvastatin, the total cholesterol level returns to the initial level observed prior to treatment. The active form of simvastatin is a specific inhibitor of HMG-CoA reductase, an enzyme that catalyzes the reaction of mevalonate formation from HMG-CoA. Since the conversion of HMG-CoA to mevalonat is an early stage of cholesterol biosynthesis, it is believed that the use of Zocor should not cause accumulation of potentially toxic sterols in the body. In addition, HMG-CoA is also easily metabolized back to acetyl-CoA, which is involved in many biosynthetic processes in the body. In a Scandinavian study of the effects of simvastatin on survival (4S), the effect of Zocor therapy on overall mortality (median patient participation time of 5.4 years) was evaluated in 4444 patients with coronary heart disease (CHD) and baseline total cholesterol levels of 212–309 mg / dL (5.5–8.0 mmol / L).In this multicenter, randomized, double-blind, placebo-controlled study Zocor reduced the risk of total mortality by 30%, mortality from coronary heart disease by 42%, the incidence of nonfatal myocardial infarctions confirmed in hospital conditions by 37%. Zocor also reduced the risk of undergoing surgery to restore blood flow (aorto-coronary bypass surgery or percutaneous transluminal coronary angioplasty) by 37%. In patients with diabetes, the risk of severe coronary complications was reduced by 55%. Moreover, Zocor significantly (28%) reduced the risk of fatal and non-fatal cerebral circulatory disorders (strokes and transient cerebral circulatory disorders). In a 5-year, multicenter, randomized, double-blind, placebo-controlled heart protection study (HeartProtectionStudy-HPS) efficacy of Zocor therapy was demonstrated on 20,536 patients with or without hyperlipidemia who are at high risk for coronary artery disease and related diseases such as diabetes mellitus, stroke, other e vascular diseases. In 33% of patients, LDL levels were lower than 116 mg / dL, 25% had LDL levels from 116 mg / dL to 135 mg / dL and 42% had LDL levels higher than 135 mg / dL. In this study, simvastatin at 40 mg / compared with placebo reduced the risk of total mortality by 13%, mortality associated with coronary artery disease by 18%, the risk of serious coronary complications (including nonfatal myocardial infarction or death associated with coronary artery disease) by 27%, the need for surgical interventions to restore coronary blood flow (including coronary artery bypass graft and percutaneous transluminal angioplasty), as well as peripheral blood flow and other types of non-coronary revascularization by 30% and 16%, respectively, by 25% - the risk of stroke. The frequency of hospitalizations for heart failure (HF) was reduced by 17%. The risk of serious coronary and vascular complications was reduced by 25% in patients with or without coronary artery disease, including patients with diabetes mellitus and patients with cardiovascular diseases, including disorders of the peripheral circulation. In patients with diabetes mellitus, Zocor reduced the risk of developing serious vascular complications by 21%, incl. the need for surgery to restore peripheral blood flow (surgical or angioplasty), amputation of the lower extremities and the occurrence of trophic ulcers. In another multicenter,A placebo-controlled study involving 404 patients using quantitative assessment of coronary blood flow in coronary angiography, Zocor slowed the progression of coronary atherosclerosis and the development of both new lesions and new total occlusions, while patients who received standard therapy for 4 years had a steady progression atherosclerotic lesions of the coronary arteries. The analysis in subgroups of 2 studies, which included 147 patients with hypercholesterolemia (hyperlipidema IV type according to Fredrickson's classification) showed that Zocor at a dose of 20 to 80 mg / day reduces the level of triglycerides to 21-39% (in the placebo group 11-13%), LDL to 23-35% (in the placebo group 1- 3%), of all lipoproteins, in addition to HDL, up to 26-43% (in the placebo group up to 1-3%) and increases HDL up to 9-14% (in the placebo group - up to 3%). In 7 patients with dysbetalipoproteinemia (hyperlipidemia Type III according to the Fredrickson classification), Zocor at a dose of 80 mg / day reduced LDL cholesterol, including LPPP to 51% (in the placebo group - up to 8%) with VLDL and LPPP to 60% (in the placebo group - up to 4%).
Pharmacokinetics
Metabolism The main active metabolites of simvastatin in plasma are betahydroxyacid and its 6'-hydroxy, 6'-hydroxymethyl, and 6'-exomethylene derivatives. Cmax in the plasma of simvastatin metabolites is achieved within 1.3-2.4 h after administration of a single dose. There is evidence of the achievement of Cmax of simvastatin and its metabolites in the period up to 4 hours and its slow decrease after about 12 hours by about 10%. When you receive simvastatin in the recommended therapeutic doses (5-80 mg / day), the linear nature of the AUC profile of active metabolites in the general circulation is preserved. Linear dependence is maintained when the dose is increased to 120 mg. Simvastatin is an inactive lactone, which is easily hydrolyzed, turning into B-hydroxyaxide, L-654,969, a potent inhibitor of HMG-CoA reductase. The blood plasma contains the metabolite L-654,969 and 4 more active metabolites. Inhibition of HMG-CoA reductase underlies all pharmacokinetic studies of metabolites of B-hydroxyoxide (active inhibitors) and, following the basis of hydrolysis, active with latent inhibitors (all inhibitors). Both are determined in the blood plasma when simvastatin is administered. About 85% of the simvastatin dose taken orally is absorbed. Distribution After ingestion in the liver, higher concentrations of simvastatin are determined than in other tissues. less than 5% of the ingested dose, 95% of this amount is in a state bound to proteins.The active metabolism of simvastatin in the liver (more than 60% in men) is its low content in the general bloodstream. The possibility of simvastatin penetration through the blood-brain barrier and the hemato-placental barrier has not been studied. Withdrawal When first passing through the hepatic bloodstream, simvastatin is metabolized and followed up with the body, simvastatin is metabolized and followed up with the heart, simvastatin is metabolized and followed up with the body, simvastatin is metabolized and followed up with the body, simvastatin is metabolized and followed up with the body, simvastatin is metabolized and followed up with the body, simvastatin is metabolized and followed up with the body, simvastatin is metabolized and followed up with the body, simvastatin is metabolized and followed up with the body, simvastatin is metabolized and treated with simvastatin. In the study, 100 mg of the drug was administered in capsules (5 x 20 mg), labeled with simvastatin C14 accumulated in the blood, urine and feces. About 60% of the labeled drug was detected in the feces and only about 13% in the urine. The coefficient of variation of the AUC in the general circulation does not depend on the dose of simvastatin. In this study, patients took inside pills of simvastatin in doses of 5, 10, 20, 60, 90, and 120 mg. Eating (as part of the standard hypocholesterol diet) immediately after taking simvastatin does not violate the pharmacokinetic profile of the drug. Pharmacokinetic indices when taking a single dose and long-term treatment with simvastatin show that simvastatin does not accumulate in the tissues with long-term treatment. Cmax inhibitors in plasma are reached within 1.3-2.4 h after taking the drug. In a study in patients with severe renal failure (clearance of kratinin less than 30 ml / min) after taking a single dose of the drug, the total number of HMG-CoA reductase inhibitors in the blood plasma were about 2 times higher than in healthy volunteers.
Indications
In patients with a high risk of developing coronary artery disease (with or without hyperlipidemia), for example, in patients with diabetes mellitus, in patients with stroke or other cerebrovascular diseases in history, in patients with peripheral vascular disease, or in patients with ischemic heart disease or predisposition to CHD Zocor is indicated for: - reducing the risk of total mortality by reducing mortality from ischemic heart disease - reducing the risk of serious vascular and coronary complications: nonfatal myocardial infarction, coronary death, stroke; - surgery - reducing the risk of the need for coronary blood flow restoration operations (such as coronary artery bypass surgery and percutaneous transluminal coronary angioplasty); reducing the risk of the need for surgery to restore peripheral blood flow and other types of non-coronary revascularization; attacks of angina pectoris. Hypercholesterolemia - as an addition to the diet,when the use of only diet and other non-medical methods of treatment is not enough to: - reduce elevated levels of total cholesterol, LDL cholesterol, triglycerides. Apolipoprotein B (apo B), - to increase HDL in patients with primary hypercholesterolemia including heterozygous familial hypercholesterolaemia (hyperlipidemia IIa type Fredrickson classification) or mixed hypercholesterolemia (hyperlipidemia IIb type Fredrickson classification) - lower LDL cholesterol ratio to cholesterol HDL and total cholesterol to HDL cholesterol; - hypertriglyceridemia (type IV hyperlipidemia according to Fredrickson classification); - supplement to diet and other treatments for patients with homozyg otnoy familial hypercholesterolemia to reduce elevated total cholesterol, LDL cholesterol and apolipoprotein B - primary disbetalipoproteinemiya (type III hyperlipidemia Fredrickson classification) .u patients with diabetes - Zocor reduces the risk of peripheral vascular events (revascularization operations, lower limb amputation, the emergence of trophic ulcers). In patients with coronary artery disease with high cholesterol, Zocor reduces the development of coronary atherosclerosis, including the development new lesions and complications.
Contraindications
- liver disease in the active phase or persistent transaminase elevation in blood plasma of unknown etiology; - pregnancy; - lactation period; - hypersensitivity to any component of the drug. With care: - many of the patients who had rhabdomyolysis during simvastatin therapy had a complicated history, including suffered from renal failure, usually due to diabetes. Such patients require more careful observation. Simvastatin therapy should be temporarily discontinued in these patients a few days before performing large surgical interventions, as well as in the postoperative period; - patients with sustained elevated serum transaminase levels exceeding 3 times the upper normal range should be discontinued; - in case of severe renal failure (creatinine clearance less than 30 ml / min), it is necessary to carefully weigh the feasibility of prescribing the drug in doses exceeding 10 mg / day.If such dosages are considered necessary, they should be prescribed with caution - alcohol abuse before the start of treatment.
Precautionary measures
Application for violations of liver functionWith caution, you should prescribe the drug for violations of the liver.It is not necessary to change the dose in case of renal dysfunction. The concentration of amplodipine in the blood plasma does not depend on the degree of reduction of renal function. Use in children It is contraindicated in children and adolescents under the age of 18. Application in elderly patients With caution in elderly patients.
Use during pregnancy and lactation
Zocor is contraindicated and should not be given to pregnant women, as well as women who are supposed to have a pregnancy or plan to do so. safety for pregnant women has not been proven and there is no evidence that treatment with Zocor during pregnancy is more beneficial than the risk to the fetus, the drug should be immediately stopped when pregnancy occurs. If pregnancy occurs during treatment with Zocor, the drug must be canceled, and the woman herself is warned about the possible danger to the fetus. There is no data on the release of simvastatin into milk, but since a small amount of other drugs of this class is released into breast milk, women taking Zocor, breastfeeding is not recommended due to the possibility of serious adverse reactions in children.
Dosage and administration
Before starting treatment with Zocor, the patient should be prescribed a standard hypocholesterol diet, which should be followed during the entire course of treatment. The recommended dose of Zocor is from 5 to 80 mg, should be taken 1 time / day in the evening. When selecting a dose of Zocor, its change should be made at intervals of not less than 4 weeks. The maximum daily dose is 80 mg. Patients with coronary heart disease (CHD) or high risk of developing coronary heart disease. The standard initial dose of Zocor for patients with a high risk of developing CHD (in combination with hyperlipidemia or without it - patients with diabetes mellitus, patients with stroke or history of other cerebrovascular diseases, patients with peripheral vascular diseases),as well as for patients with ischemic heart disease or the risk of its occurrence is 40 mg / day 1 time / day in the evening. Drug therapy should be started simultaneously with the use of diet and physical therapy. Patients with hypercholesterolemia (not included in the risk categories above) are usually the initial dose is 20 mg / day, which is appointed once a day in the evening. For patients who need a significant (more than 45%) decrease in the level of LDL, the initial dose may be 40 mg 1 time / day. Patients with mild or moderate hypercholesterolemia can be prescribed Zocor in an initial dose of 10 mg. Selection of doses, if necessary, should be carried out in the manner outlined above. Patients with homozygous familial hypercholesterolemia. The dose is recommended in a dose of 40 mg / day, taken once in the evening, or 80 mg / day in 3 doses: 20 mg in the morning, 20 mg in the afternoon and 40 mg in the evening. In these patients, Zocor is used as an adjunct to another treatment that reduces cholesterol (for example, LDL plasmapheresis) or without other treatment if it is not available. Concomitant therapy It is recommended to use it as a monotherapy or in combination with bile acid sequestrants. In patients taking cyclosporine, danazol, gemfibrozil or other fibrates (except fenofibrate), or lipid-lowering doses (> 1 g / day) of niacin in conjunction with Zocor, the maximum recommended dose of Zocor is 10 mg / day. For patients who are taking amiodarone or verapamil at the same time as Zocor, the daily dose of Zocor should not exceed 20 mg. In case of renal failure. Since Zocor is excreted in small amounts by the kidneys, there is no need to change the dosage in patients suffering from moderately severe renal failure. In severe renal failure (creatinine clearance less than 30 ml / min), the expediency of administering the drug in doses exceeding 10 mg / day should be carefully weighed. If such dosages are deemed necessary, they should be administered with caution.
Side effects
Zocor is generally well tolerated, side effects are generally mild and transient. Less than 2% of patients were excluded from clinical studies due to the developmental assumption associated with the use of Zocor,side effects. Before the widespread use of the drug, adverse effects that occur with a frequency of 1% or more, which were evaluated by researchers as possibly, probably or definitely related to taking the drug, were abdominal pain, constipation and flatulence. Other side effects that occur in 0.5-0.9% of patients were asthenia and headache. There were rare reports of the development of myopathy. The widespread use of Zocor at a dose of 40 mg / day for 5 years in a study on the protection of the heart (HPS) confirmed the compatibility of the safety profile of Zocor in patients receiving Zocor (n = 10269) and not receiving the drug (n = 10267): refusal of treatment as a result of adverse events was 4.8% in the group of patients who received Zocor and 5.1% in the group of patients who received placebo. The incidence of myopathy in patients receiving Zocor was less than 0.1%. Increased liver transaminase activity (more than 3 times the upper limit of normal and confirmed by repeated research) - 0.21% of patients who received Zocor and 0.09% of patients who received placebo. In a Scandinavian study (4S, n = 4444), safety profiles and tolerability was comparable in patients taking Zocor (n = 2221) at a dose of 20-40 mg and in patients of the placebo group (n = 2223) when observing these patients for more than 5.4 years. There are reports of the possibility of the following side effects: Digestive systems: var psiya (nausea, vomiting, diarrhea); rarely - hepatitis and jaundice, pancreatitis. From the side of the CNS: dizziness, peripheral neuropathy. From the musculoskeletal system: myalgia; rarely, rhabdomyolis and allergy and immunopathy; , alopecia, dermatomyositis. Others: anemia, general malaise, muscle cramps, paresthesias. Laboratory indicatorsThere are rare reports of the development of pronounced and persistent increases in tra nsaminase. An increase in alkaline phosphatase and gamma-glutamyltranspeptidase activity has also been reported.Deviations in the performance of functional liver samples are usually mild and transient. There is evidence of cases of increased activity of creatine phosphokinase.
Overdose
Several cases of overdose have been reported, the maximum accepted dose was 3.6 g. In no patient, the effects of overdose have been identified. General measures, including supportive and symptomatic therapy, are used to treat overdose.
Interaction with other drugs
Simvastatin is metabolized by CYP3A4; however, it does not have inhibitory activity against this coenzyme, which suggests that the administration of simvastatin does not affect the plasma concentration of drugs metabolized by CYP3A4. Potent inhibitors of CYP3A4 (see below) increase the risk of myopathy by reducing the rate of simvastatin elimination. These include treraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone. The risk of developing myopathy / rhabdomyolysis is increased when co-administered with cyclosporine or danazol with high doses of simvastatin. Other lipid-lowering drugs that can cause the development of myopathy. The risk of developing myopathy is increased as a result of the concomitant use of other lipid-lowering drugs that are not strong CYP3A4 inhibitors, but can cause myopathy in monotherapy. Such drugs are gemfibrozil and other fibrates (except for fenofibrate, when combined with simvastatin, the risk of myopathy does not exceed that with monotherapy for each drug), as well as lipid-lowering doses (> 1 g / day) of niacin (nicotinic acid). The risk of myopathy development increases due to concomitant administration of amiodarone or verapamil with high doses of simvastatin. The risk of myopathy increases slightly in patients receiving diltiazem simultaneously with simvastatin at a dose of 80 mg.C Imvastatin at a dose of 20–40 mg / day potentiates the effect of coumarin anticoagulants and increases the risk of bleeding: the prothrombin time, defined as the International Normal Ratio (INR), increases from a baseline of 1.7 to 1.8 in healthy volunteers, and from 2.6 to 3.4 in patients, suffering from hypercholesterolemia.In patients taking coumarin anticoagulants, the prothrombin time should be determined before starting therapy with simvastatin, as well as quite often in the initial period of treatment to exclude significant changes in this indicator. As soon as a stable level of prothrombin time is reached, its further determination should be carried out at intervals recommended for monitoring patients receiving anticoagulant therapy. The same procedure should be repeated when changing the dosage or discontinuation of simvastatin. In patients who did not take anticoagulants, simvastatin therapy was not associated with the occurrence of bleeding or changes in prothrombin time. Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase plasma levels of drugs metabolized by CYP3A4. The effect of the usual use of juice (one glass of 250 ml / day) is minimal (a 13% increase in the activity of HMG-CoA reductase inhibitors based on the measurement of the area under the concentration-time curve) and has no clinical significance. However, very large amounts of juice consumption (more than 1 l / day) significantly increase the plasma level of activity of HMG-CoA reductase inhibitors during therapy with simvastatin. In this regard, it is necessary to avoid the consumption of grapefruit juice in large volumes.
special instructions
Data on the efficacy and safety of use in children is not enough, therefore, use in children is not recommended. (more than 10 times the upper limit of the norm). Myopathy can manifest itself in the form of rhabdomyolysis, sometimes accompanied by secondary acute renal failure caused by myoglobinuria, in rare cases leading to death. The risk of myopathy is increased by increasing the concentration in the blood plasma of substances with an inhibitory effect on HMG-CoA reductase. The risk of myopathy / rhabdomyolysis in the treatment with simvastatin is increased due to the concomitant use of the following drugs:ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors and nefazodone, especially in combination with high doses of simvastatin; gemfibrozil and other fibrates (except fenofibrate), as well as lipid-lowering doses (> 1 g / day) niacin (nicotine acid) , especially in combination with high doses of simvastatin. There is no evidence that when prescribing simvastatin simultaneously with fenofibrate, the risk of myopathy exceeds the total risk posed by taking each of these drugs; - cyclosporine or danazol - the risk of myopathy / rhabdomyolysis increases, especially when prescribing high doses of Zocor; - amiodarone or verapamil in combination with high doses of simvastatin. In clinical studies, myopathy was reported in 6% of patients who received both 80 mg simvastatin and amiodarone at the same time - the risk of myopathy in patients receiving diltiazem at the same time as 80 mg symvastatin is slightly increased and is approximately 1%. The risk of developing myopathy in patients receiving diltiazem simultaneously with simvastatin at a dose of 40 mg was approximately the same as the risk of developing myopathy in patients who received simvastatin therapy at a dose of 40 mg without concomitant use of diltiazem. The dose of myopathy / rhabdomyolysis was dependent on the dose of the drug In clinical studies with monitoring, controlling the absence of any concomitant therapy, the incidence of myopathy / rhabdomyolysis was approximately 0.03% among patients who received simvastatin in doses e 20 mg / day, 0.08% among patients receiving simvastatin at a dose of 40 mg / day and 0.4% in patients receiving simvastatin at a dose of 80 mg / day. Measures to reduce the risk of myopathy / rhabdomyolysis1. The simultaneous use of simvastatin with the following drugs should be avoided: itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors and nefazodone. If the therapy with the listed drugs cannot be canceled, you should stop taking simvastatin for the duration of the course of treatment with these drugs. The concomitant use of any of the listed CYP3A4 inhibitors at therapeutic doses should be excluded if the benefits of such a combination therapy do not exceed the possible risk.The dose of simvastatin should not exceed 10 mg / day for patients who take cyclosporin, danazol or gemfibrozil or other fibrates (except fenofibrate), or lipid-lowering doses (> 1 g / day) of niacin (nicotinic acid). Simultaneous administration of simvastatin with these drugs should be avoided, unless the benefits of influencing lipid levels exceed the risk of using such drug combinations. Supplementing therapy with simvastatin by taking fibrates or niacin, as a rule, provides a slight additional decrease in the concentration of LDL, however, an additional decrease in the TG level and an increase in the concentration of HDL can be also achieved.3. Doses of simvastatin for patients receiving both amiodarone or verapamil should not exceed 20 mg / day. The simultaneous use of simvastatin in doses of more than 20 mg mg / day with amiodarone or verapamil should be excluded, unless the benefits of using this combination do not exceed the potential risk of developing myopathy. All patients who start therapy with simvastatin, as well as patients who need to increase the dose, should be warned of the possibility of myopathy and informed of the need for immediate treatment to the doctor in case of any unexplained pain or muscle pain or muscle weakness. Simvastatin therapy should be immediately discontinued if myopathy is diagnosed or even supposed. The presence of the above symptoms and / or more than 10-fold increase in the concentration of creatine phosphokinase compared to the upper limit of the norm indicates the presence of myopathy. In most cases, after the immediate discontinuation of simvastatin, the symptoms of myopathy are resolved, and the concentration of creatine phosphokinase decreases. In patients who start taking simvastatin or are switching to higher doses of the drug, it is advisable to periodically determine the concentration of creatine phosphokinase, but there is no guarantee that such monitoring can prevent the development of myopathy. Many of the patients who underwent rhabdomyolysis during simvastatin therapy had a complicated history, including those suffering from renal failure, as a rule, due to diabetes mellitus. Such patients require more careful observation.Simvastatin therapy should be temporarily discontinued in patients a few days before performing large surgical interventions, as well as in the postoperative period. In patients receiving coumarin anticoagulants, the prothrombin time should be monitored before initiating therapy with simvastatin and in the initial period of treatment to exclude significant changes indicator. As soon as a stable level of prothrombin time is reached, its further determination should be carried out at intervals recommended for monitoring patients receiving anticoagulant therapy. The same procedure should be repeated when changing the dosage or discontinuation of simvastatin. In patients who did not take anticoagulants, simvastatin therapy was not associated with the occurrence of bleeding or changes in prothrombin time. Effect on the liver In clinical studies, several adult patients treated with simvastatin showed a steady increase in liver enzymes (more than 3 times the upper limit of normal) . Upon termination or interruption of the administration of the drug, transaminase activity usually gradually returns to its original level. Increased transaminase levels are not associated with jaundice or other clinical symptoms, but may be due to a deviation in the results of functional liver tests and / or alcohol abuse before the start of treatment. No hypersensitivity reactions were detected. In the 4S study, the number of patients with more than one increase in serum transaminase levels (more than 3 times the upper limit of the norm) did not differ significantly in the groups taking 0.7% and 0.6% simvastatin and placebo. Increased serum transaminase levels caused cessation of treatment in 8 patients (out of 2221) in the simvastatin group and in 5 patients (out of 2223) in the placebo group. All patients in this study received an initial dose of 20 mg of simvastatin, in 37% the dose was increased to 40 mg. In 2 controlled clinical studies on 1105 patients, a persistent increase in transaminase level associated with the use of the drug was observed in 0.7% and 1.8% of cases when receiving 40 mg and 80 mg of the drug, respectively. In the HPS study on 20,536 patients while taking Zocor at a dose of 40 mg / day, an increase in serum transaminase levels (more than 3 times the upper limit of the norm) was 0.21% (n = 21) and 0.09% (n = 9) in groups that took simvastatin and p placebo, respectively. Before starting treatment,and then, in accordance with the clinical indications, all patients are recommended to conduct a study of the function of the liver. Patients in whom it is planned to increase the dose of simvastatin to 80 mg / day should conduct additional studies of liver function before proceeding to the indicated dosage, 3 months after the start of its use and then periodically repeat (for example, 1 time / six months) during the first years of treatment. Particular attention should be paid to patients with