Release form, composition and packing
Film-coated tablets from light pink to pink with sirenevatym shade, round, biconvex, on a cross-section - almost white.
1 tab. simvastatin 20 mg.
Excipients: potato starch, lactose monohydrate, ascorbic acid, butylate gidroksitoluen, citric acid anhydrous, pregelatinized starch, magnesium stearate. The composition of the shell: talc, hypromellose, hydroxypropyl cellulose, titanium dioxide, dye acid red.
Clinico-pharmacological group: Lipid-lowering drug.
Pharmacological action
Lipid-lowering agent derived synthetically from a product of fermentation Aspergillus terreus. Is an inactive lactone, is hydrolyzed in the body to form gidroksikislotnogo derivative. Active metabolite inhibits 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-KoA-reductase) enzyme that catalyzes the initial reaction of mevalonate from HMG-CoA. Since the conversion of HMG-KoA to mevalonate is an early stage of the synthesis of cholesterol (CH), the use of simvastatin does not cause the accumulation in the body of potentially toxic sterols. HMG-KoA readily metabolized to acetyl-CoA, which is involved in many processes of synthesis in the body.
Reduces the concentration of TG, LDL, VLDL and total cholesterol (TCH) in plasma (in cases of heterozygous familial hypercholesterolemia and non-family forms, with mixed hyperlipidemia, when the rise in HDL is a risk factor). Reduces the ratio of LDL / HDL and total XC / HDL. Onset of action - after 2 weeks. from the beginning of the reception, the maximum therapeutic effect - in 4-6 weeks. Effect persists for continuing treatment, with cessation of therapy, HDL is returned to its original level (before treatment).
Pharmacokinetics
Absorption and distribution
After ingestion simavstatin highly absorbed from the gastrointestinal tract. After oral administration, C max reached after 1.3-2.4 h and is reduced by 90% after 12 h. The binding to plasma proteins is 95%.
Metabolism and Elimination
Simvastatin undergoes the effect of "first passage" through the liver. Hydrolyzed mainly to its active form of beta-hydroxy acids. Also found other active and inactive metabolites.
Metabolism is carried out with the participation of isozymes CYP3A4, CYP3A5 and CYP3A7. T1 / 2 of active metabolite is 1.9 hours, is derived mainly from the feces (60%) as metabolites. About 10-15% is excreted by the kidneys in an inactive form.
Statement
primary hypercholesterolaemia IIa and IIb type (with the ineffectiveness of diet therapy in patients with increased risk of coronary atherosclerosis), combined hypercholesterolemia and hypertriglyceridemia, hyperlipoproteinemia, beyond the correction of a special diet and physical activity.
prevention of myocardial infarction (to slow the progression of coronary atherosclerosis), stroke and transient ischemic.
Dosing regimen
Tablets taken orally, 1 time per day in the evening. In mild to moderate hypercholesterolemia starting dose is 5 mg / day in severe hypercholesterolemia - 10 mg / day. If necessary, may increase the dose no earlier than 4 weeks. The maximum daily dose - 80 mg.
Coronary heart disease starting dose - 20 mg, if necessary, gradually increase the dose every 4 weeks. to 40 mg. If the concentration of LDL cholesterol below 75 mg / dL (1.94 mmol / l), the concentration of total cholesterol less than 140 mg / dL (3.6 mmol / L) dose should be reduced. In patients with chronic renal insufficiency (creatinine clearance less than 30 ml / min) or while the application of fibrates, nicotinic acid (or nicotinamide), the initial dose - 5 mg, the maximum daily dose - 10 mg. On the background of immunosuppressive therapy (eg, cyclosporine) recommended initial dose of 5 mg / day. The maximum daily dose is 5 mg. In case of missing the current dose should be taken as soon as possible. If the time the next dose, dose does not double.
Side effect
From the digestive system: dyspepsia (nausea, vomiting, stomachodynia, abdominal pain, constipation, diarrhea, flatulence), hepatitis, jaundice, elevated liver transaminases, alkaline phosphatase, CPK, rarely - acute pancreatitis.
CNS and peripheral nervous system: asthenic syndrome, dizziness, headache, insomnia, muscle cramps, paresthesia, peripheral neuropathy, blurred vision, impaired sense of taste.
From the musculoskeletal system: myopathy, myalgia, muscle weakness, rarely - rhabdomyolysis.
Allergic and immunopathological reactions: angioedema, volchanochnopodobny syndrome, polymyalgia rheumatica, vasculitis, thrombocytopenia, eosinophilia, increased ESR, arthritis, arthralgia, urticaria, photosensitivity, fever, skin redness, flushing, shortness of breath.
Dermatological reactions: skin rash, itching, alopecia.
Other: anemia, heart palpitations, acute renal failure (due to rhabdomyolysis), a decrease in potency.
Contraindications
liver failure;
acute liver disease;
elevated liver transaminases of unknown origin;
age 18 (safety and efficacy not established);
pregnancy;
Lactation (breastfeeding);
hypersensitivity to the drug;
increased sensitivity to other drugs in a number of statin (inhibitors of HMG-CoA reductase) in history.
With carefully administered to persons who abuse alcohol and / or having a history of liver disease in patients after organ transplantation, which is immunosuppressive therapy (in conjunction with an increased risk of rhabdomyolysis and renal failure), with conditions that can lead to severe renal insufficiency (hypotension, acute infectious disease severe expressed metabolic and endocrine disorders, disorders of water and electrolyte balance, surgery / including dental / injury), patients with decreased or increased muscle tone of unknown etiology, with epilepsy.
Pregnancy and lactation
The drug is contraindicated in pregnancy. Due to the fact that inhibitors of HMG-CoA reductase inhibitors inhibit the synthesis of cholesterol and cholesterol and other products of its synthesis play an important role in fetal development, including synthesis of steroids and cell membranes, simvastatin may have adverse effects on the fetus in the appointment of pregnancy (women reproductive age should avoid conception). If in the course of treatment there is pregnancy, the drug should be withdrawn and the woman advised of the possible danger to the fetus.
Cancel lipid-lowering drugs during pregnancy did not significantly affect the results of long-term treatment of primary hypercholesterolemia. If necessary, use during lactation should decide the issue of termination of breastfeeding.
Use in hepatic dysfunction
The drug is contraindicated in hepatic insufficiency; acute liver diseases and an increase in liver transaminases of unknown origin.
With carefully administered to persons who abuse alcohol and / or having a history of liver disease.
Use in renal impairment
In patients with chronic renal insufficiency (creatinine clearance less than 30 ml / min), the initial dose - 5 mg, the maximum daily dose - 10 mg.
Cautions
In the event of myalgia, myasthenia gravis and / or a pronounced increase in the activity of CK treatment drug is discontinued. Aterostat (like other inhibitors of HMG-KoA-reductase inhibitors) should not be used at higher risk of rhabdomyolysis and renal failure (due to severe acute infection, hypotension, a big surgery, trauma, severe metabolic disorders). Aterostat not shown in those cases where there hypertriglyceridemia I, IV and V types. The drug is effective as monotherapy and in combination with bile acid sequestrants.
Prior to and during treatment the patient should be on hypolipidemic diet. Patients are advised to promptly report unexplained muscle pain, lethargy or weakness, especially if it is accompanied by malaise or fever.
Monitoring of laboratory parameters
Before treatment is necessary to conduct a study of liver function, and then monitor the activity of liver enzymes every 6 weeks during the first 3 months, then every 8 weeks during the remainder of the first year and then one every six months.
Patients receiving simvastatin 80 mg daily dose, liver function monitor 1 every 3 months. In cases where the activity of hepatic transaminase increases (exceeding 3 times ULN), a drug overturned. Patients with severe renal insufficiency treatment is carried out under the control of renal function.
Overdose
Treatment: should induce vomiting, take activated charcoal, shown holding a symptomatic therapy. Should monitor the liver and kidney function, the content of CK in serum.
Drug Interactions
In a joint application with simvastatin increases the effect of indirect anticoagulants and increase the risk of bleeding.
In a joint application with simvastatin cytotoxic agents, antifungals (ketoconazole, itraconazole), fibrates, niacin in high doses, immunosuppressants, erythromycin, clarithromycin, protease inhibitors increase the risk of rhabdomyolysis.
Together, simvastatin enhances the concentration of digoxin in plasma.
Film-coated tablets from light pink to pink with sirenevatym shade, round, biconvex, on a cross-section - almost white.
1 tab. simvastatin 20 mg.
Excipients: potato starch, lactose monohydrate, ascorbic acid, butylate gidroksitoluen, citric acid anhydrous, pregelatinized starch, magnesium stearate. The composition of the shell: talc, hypromellose, hydroxypropyl cellulose, titanium dioxide, dye acid red.
Clinico-pharmacological group: Lipid-lowering drug.
Pharmacological action
Lipid-lowering agent derived synthetically from a product of fermentation Aspergillus terreus. Is an inactive lactone, is hydrolyzed in the body to form gidroksikislotnogo derivative. Active metabolite inhibits 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-KoA-reductase) enzyme that catalyzes the initial reaction of mevalonate from HMG-CoA. Since the conversion of HMG-KoA to mevalonate is an early stage of the synthesis of cholesterol (CH), the use of simvastatin does not cause the accumulation in the body of potentially toxic sterols. HMG-KoA readily metabolized to acetyl-CoA, which is involved in many processes of synthesis in the body.
Reduces the concentration of TG, LDL, VLDL and total cholesterol (TCH) in plasma (in cases of heterozygous familial hypercholesterolemia and non-family forms, with mixed hyperlipidemia, when the rise in HDL is a risk factor). Reduces the ratio of LDL / HDL and total XC / HDL. Onset of action - after 2 weeks. from the beginning of the reception, the maximum therapeutic effect - in 4-6 weeks. Effect persists for continuing treatment, with cessation of therapy, HDL is returned to its original level (before treatment).
Pharmacokinetics
Absorption and distribution
After ingestion simavstatin highly absorbed from the gastrointestinal tract. After oral administration, C max reached after 1.3-2.4 h and is reduced by 90% after 12 h. The binding to plasma proteins is 95%.
Metabolism and Elimination
Simvastatin undergoes the effect of "first passage" through the liver. Hydrolyzed mainly to its active form of beta-hydroxy acids. Also found other active and inactive metabolites.
Metabolism is carried out with the participation of isozymes CYP3A4, CYP3A5 and CYP3A7. T1 / 2 of active metabolite is 1.9 hours, is derived mainly from the feces (60%) as metabolites. About 10-15% is excreted by the kidneys in an inactive form.
Statement
primary hypercholesterolaemia IIa and IIb type (with the ineffectiveness of diet therapy in patients with increased risk of coronary atherosclerosis), combined hypercholesterolemia and hypertriglyceridemia, hyperlipoproteinemia, beyond the correction of a special diet and physical activity.
prevention of myocardial infarction (to slow the progression of coronary atherosclerosis), stroke and transient ischemic.
Dosing regimen
Tablets taken orally, 1 time per day in the evening. In mild to moderate hypercholesterolemia starting dose is 5 mg / day in severe hypercholesterolemia - 10 mg / day. If necessary, may increase the dose no earlier than 4 weeks. The maximum daily dose - 80 mg.
Coronary heart disease starting dose - 20 mg, if necessary, gradually increase the dose every 4 weeks. to 40 mg. If the concentration of LDL cholesterol below 75 mg / dL (1.94 mmol / l), the concentration of total cholesterol less than 140 mg / dL (3.6 mmol / L) dose should be reduced. In patients with chronic renal insufficiency (creatinine clearance less than 30 ml / min) or while the application of fibrates, nicotinic acid (or nicotinamide), the initial dose - 5 mg, the maximum daily dose - 10 mg. On the background of immunosuppressive therapy (eg, cyclosporine) recommended initial dose of 5 mg / day. The maximum daily dose is 5 mg. In case of missing the current dose should be taken as soon as possible. If the time the next dose, dose does not double.
Side effect
From the digestive system: dyspepsia (nausea, vomiting, stomachodynia, abdominal pain, constipation, diarrhea, flatulence), hepatitis, jaundice, elevated liver transaminases, alkaline phosphatase, CPK, rarely - acute pancreatitis.
CNS and peripheral nervous system: asthenic syndrome, dizziness, headache, insomnia, muscle cramps, paresthesia, peripheral neuropathy, blurred vision, impaired sense of taste.
From the musculoskeletal system: myopathy, myalgia, muscle weakness, rarely - rhabdomyolysis.
Allergic and immunopathological reactions: angioedema, volchanochnopodobny syndrome, polymyalgia rheumatica, vasculitis, thrombocytopenia, eosinophilia, increased ESR, arthritis, arthralgia, urticaria, photosensitivity, fever, skin redness, flushing, shortness of breath.
Dermatological reactions: skin rash, itching, alopecia.
Other: anemia, heart palpitations, acute renal failure (due to rhabdomyolysis), a decrease in potency.
Contraindications
liver failure;
acute liver disease;
elevated liver transaminases of unknown origin;
age 18 (safety and efficacy not established);
pregnancy;
Lactation (breastfeeding);
hypersensitivity to the drug;
increased sensitivity to other drugs in a number of statin (inhibitors of HMG-CoA reductase) in history.
With carefully administered to persons who abuse alcohol and / or having a history of liver disease in patients after organ transplantation, which is immunosuppressive therapy (in conjunction with an increased risk of rhabdomyolysis and renal failure), with conditions that can lead to severe renal insufficiency (hypotension, acute infectious disease severe expressed metabolic and endocrine disorders, disorders of water and electrolyte balance, surgery / including dental / injury), patients with decreased or increased muscle tone of unknown etiology, with epilepsy.
Pregnancy and lactation
The drug is contraindicated in pregnancy. Due to the fact that inhibitors of HMG-CoA reductase inhibitors inhibit the synthesis of cholesterol and cholesterol and other products of its synthesis play an important role in fetal development, including synthesis of steroids and cell membranes, simvastatin may have adverse effects on the fetus in the appointment of pregnancy (women reproductive age should avoid conception). If in the course of treatment there is pregnancy, the drug should be withdrawn and the woman advised of the possible danger to the fetus.
Cancel lipid-lowering drugs during pregnancy did not significantly affect the results of long-term treatment of primary hypercholesterolemia. If necessary, use during lactation should decide the issue of termination of breastfeeding.
Use in hepatic dysfunction
The drug is contraindicated in hepatic insufficiency; acute liver diseases and an increase in liver transaminases of unknown origin.
With carefully administered to persons who abuse alcohol and / or having a history of liver disease.
Use in renal impairment
In patients with chronic renal insufficiency (creatinine clearance less than 30 ml / min), the initial dose - 5 mg, the maximum daily dose - 10 mg.
Cautions
In the event of myalgia, myasthenia gravis and / or a pronounced increase in the activity of CK treatment drug is discontinued. Aterostat (like other inhibitors of HMG-KoA-reductase inhibitors) should not be used at higher risk of rhabdomyolysis and renal failure (due to severe acute infection, hypotension, a big surgery, trauma, severe metabolic disorders). Aterostat not shown in those cases where there hypertriglyceridemia I, IV and V types. The drug is effective as monotherapy and in combination with bile acid sequestrants.
Prior to and during treatment the patient should be on hypolipidemic diet. Patients are advised to promptly report unexplained muscle pain, lethargy or weakness, especially if it is accompanied by malaise or fever.
Monitoring of laboratory parameters
Before treatment is necessary to conduct a study of liver function, and then monitor the activity of liver enzymes every 6 weeks during the first 3 months, then every 8 weeks during the remainder of the first year and then one every six months.
Patients receiving simvastatin 80 mg daily dose, liver function monitor 1 every 3 months. In cases where the activity of hepatic transaminase increases (exceeding 3 times ULN), a drug overturned. Patients with severe renal insufficiency treatment is carried out under the control of renal function.
Overdose
Treatment: should induce vomiting, take activated charcoal, shown holding a symptomatic therapy. Should monitor the liver and kidney function, the content of CK in serum.
Drug Interactions
In a joint application with simvastatin increases the effect of indirect anticoagulants and increase the risk of bleeding.
In a joint application with simvastatin cytotoxic agents, antifungals (ketoconazole, itraconazole), fibrates, niacin in high doses, immunosuppressants, erythromycin, clarithromycin, protease inhibitors increase the risk of rhabdomyolysis.
Together, simvastatin enhances the concentration of digoxin in plasma.
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