Simvastatin 10 mgvspomogatelnye substances: lactose (milk sugar), microcrystalline cellulose, povidone (polyvinylpyrrolidone), citric acid, ascorbic acid, butylhydroxyanisole, corn starch, calcium stearate, hypromellose (hydroxypropylmethylcellulose), macrogol 4000, talc, titanium dioxide.
The lipid-lowering agent, obtained synthetically from the fermentation product Aspergillus terreus, is an inactive lactone, undergoes hydrolysis in the body to form 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 the formation of mevalonate from HMG-CoA. Since the transformation of HMG-CoA into mevalonat is an early stage of cholesterol synthesis, 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 body synthesis processes. It causes a decrease in plasma levels of triglycerides (TG), low density lipoproteins (LDL), very low density lipoproteins (VLDL) and total cholesterol (in cases of heterozygous familial and nonfamily forms of hypercholesterolemia, with mixed hyperlipidemia, when elevated cholesterol is a risk factor). Increases the content of high-density lipoprotein (HDL) and reduces the ratio of LDL / HDL and total cholesterol / HDL. The effect begins - 2 weeks from the start of treatment, the maximum therapeutic effect is achieved after 4-6 weeks. The effect persists with continued treatment, with the termination of therapy, the cholesterol content gradually returns to its original level.
Simvastatin absorption is high. After ingestion, Cmax in the blood plasma is reached in about 1.3-2.4 hours and decreases by 90% in 12 hours. Binding to plasma proteins is about 95%. It is metabolized in the liver, has the effect of "first passage" through the liver (hydrolyzes to form active derivative: beta-hydroxy acids, other active as well as inactive metabolites are found).T1 / 2 active metabolites is 1.9 hours. It is displayed mainly with feces (60%) in the form of metabolites. About 10-15% is excreted by the kidneys in an inactive form.
Hypercholesterolemia: - primary hypercholesterolemia (type IIa and IIb) with the ineffectiveness of dietary therapy with low cholesterol and other non-drug measures (exercise and weight loss) in patients with an increased risk of developing coronary atherosclerosis; physical exertion. Ischemic heart disease: - for the prevention of myocardial infarction, to reduce the risk of death, reduce the risk of cardiovascular disease abnormalities (stroke or transient ischemic attacks), slowing the progression of coronary atherosclerosis, reducing the risk of revascularization procedures.
- liver diseases in the active phase, persistent increase in liver enzymes of unknown etiology; - skeletal muscle diseases (myopathy); - age up to 18 years (efficacy and safety not established); - hypersensitivity to simvastatin or to other components of the drug (in t. h. hereditary intolerance to lactose), as well as to other statin drugs (inhibitors of HMC-CoA reductase) in history. With caution prescribed to patients who abuse alcohol, patients after organ transplantation m performed immunosuppressive therapy (due to an increased risk of rhabdomyolysis and renal failure); in conditions that can lead to the development of severe kidney function deficiency, such as arterial hypotension, acute severe infectious diseases, pronounced metabolic and endocrine disorders, disturbances of water and electrolyte balance, surgical interventions (including dental) or injuries; patients with reduced or elevated skeletal muscle tone of unknown etiology; epilepsy.
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
Simvastatin is contraindicated in pregnant women. There are several reports of the development of anomalies in newborns whose mothers took simvastatin. Women of childbearing age who take simvastatin should avoid conception. If, in the course of treatment, the pregnancy has nevertheless occurred, Simvastatin should be canceled, and the woman should be warned of the possible danger to the fetus. There are no data on the release of simvastatin with mother's milk. If necessary, the appointment of Simvastatin during lactation should take into account that many drugs are excreted in breast milk, and there is a risk of severe reactions, so breastfeeding while taking the drug is not recommended.
Dosage and administration
Prior to the treatment of Simvastatin, the patient should be prescribed a standard hypocholesterol diet, which should be followed during the entire course of treatment. Simvastatin should be taken orally once a day in the evening, drinking plenty of water. The time of taking the drug should not be associated with food intake. The recommended dose of Simvastatin for the treatment of hypercholesterolemia varies from 10 to 80 mg 1 time per day in the evening. The recommended initial dose for patients with hypercholesterolemia is 10 mg. The maximum daily dose - 80 mg. Changes (selection) dose should be carried out at intervals of 4 weeks. In most patients, the optimal effect is achieved when taking the drug in doses up to 20 mg / day. In patients with homozygous hereditary hypercholesterolemia, the recommended daily dose of simvastatin is 40 mg 1 time / day in the evening or 80 mg in three doses (20 mg in the morning, 20 mg in the afternoon and 40 mg in the evening). When treating patients with coronary heart disease (CHD) or at high risk of developing CHD, the effective dose of Simvastatin is 20-40 mg / day. Therefore, the recommended initial dose in such patients is 20 mg / day. Changes (selection) of the dose should be carried out at intervals of 4 weeks, if necessary, the dose can be increased to 40 mg / day.If the content of LDL is less than 75 mg / dl (1.94 mmol / l), the total cholesterol content is less than 140 mg / dl (3.6 mmol / l), the dose of the drug should be reduced. In elderly patients and in patients with mild or moderately severe renal failure to change the dosage of the drug is not required. In patients with chronic renal failure (creatinine clearance less than 30 ml / min) or receiving cyclosporine, danazol, gemfibrozil or other fibrates (except fenofibrate), niacin in lipid-lowering doses (1 g / day) in combination with simvastatin max But the recommended dose of simvastatin should not exceed 10 mg / day. For patients taking amiodarone or verapamil simultaneously with simvastatin, the daily dose should not exceed 20 mg.
On the part of the digestive system: possible abdominal pain, constipation, flatulence, nausea, diarrhea, pancreatitis, vomiting, hepatitis, increased activity of liver enzymes, alkaline phosphokinase and creatine phosphokinase (CPK). , muscle cramps, paresthesias, peripheral neuropathy, blurred vision, impaired taste sensations. Allergic and immunopathological reactions: angioedema, rheumatic polymyalgia, vasculitis, thrombocytopenia, an increase ESR, fever, arthritis, urticaria, photosensitivity, skin flushes, hot flashes, shortness of breath, lupus-like syndrome, eosinophilia. Dermatological reactions: rarely skin rash, pruritus, alopecia, dermatomyositis. ; rarely - rhabdomyolysis. Others: anemia, palpitations, acute renal failure (due to rhabdomyolysis), reduced potency.
None of the known several cases of overdose (maximum dose of 450 mg) showed any specific symptoms. Treatment: induce vomiting, take activated charcoal, conduct symptomatic therapy. Liver and kidney function, serum CK levels should be monitored. With the development of myopathy with rhabdomyolysis and acute renal failure (a rare but severe side effect), the drug should be stopped immediately and a diuretic and sodium bicarbonate should be given to the patient (intravenous infusion).If necessary, hemodialysis is indicated. Rhabdomyolysis can cause hyperkalemia, which can be eliminated by intravenous administration of calcium chloride or calcium gluconate, infusion of glucose with insulin, the use of potassium ion exchangers or, in severe cases, by hemodialysis.
Interaction with other drugs
Cytotoxic agents, antifungal agents (ketoconazole, itraconazole), fibrates, high doses of nicotinic acid, immunosuppressants, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone increase the risk of myopathy. or danazol with high doses of simvastatin. Other lipid-lowering drugs that can cause the development of myopathy: the risk of developing myopathy increases with the joint appointment of a friend x hypolipidemic agents that are not potent inhibitors of CYP3A4, but can cause myopathy monotherapy conditions. Such as gemfibrozil and other fibrates (except 1 g of fenofibrate), as well as niacin (nicotinic acid) at a dose of more than 1 g / day. Amiodarone and verapamil: the risk of myopathy increases when co-administering amiodarone or verapamil with high doses of simvastatin. Diltiazem: risk development of myopathy slightly increases in patients receiving diltiazem simultaneously with simvastatin at a dose of 80 mg. Simvastatin potentiates the action of oral anticoagulants (eg, fenprocumon, warfarin) and increases the risk of bleeding, which requires the need to monitor blood clotting parameters prior to treatment, as well as quite often in the initial period of therapy. As soon as a stable level of prothrombin time or the International Normalized Attitude (INR) is reached, further monitoring should be carried out at intervals recommended for patients receiving anticoagulant therapy. If you change the dosage or stop taking simvastatin, you should also monitor the prothrombin time or INR by the above scheme. Simvastatin therapy does not cause changes in the prothrombin time and the risk of bleeding in patientsDo not take anticoagulants. Increases the level of digoxin in the blood plasma. Colestiramine and colestipol reduce bioavailability (use of simvastatin is possible 4 hours after taking these drugs, while there is an additive effect). Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase concentration in blood plasma of CYP3A4 metabolized agents. 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, consuming a large volume of juice (more than 1 liter per day) while taking simvastatin significantly increases the level of inhibitory activity against HMG-CoA reductase in plasma. In this regard, it is necessary to avoid the consumption of grapefruit juice in large quantities.
At the beginning of therapy with simvastatin, a transient increase in liver enzymes is possible. Before starting therapy and then regularly conduct a study of the liver (monitor the activity of liver enzymes every 6 weeks for the first 3 months, then every 8 weeks for the remaining first year, and then 1 time every 6 months), as well as with increasing doses should be carried out liver function test. If you increase the dose to 80 mg, you need to test every 3 months. With a persistent increase in transaminase activity (3 times compared to baseline), taking Simvastatin should be discontinued. Simvastatin, like other HMG-CoA reductase inhibitors, should not be used with an increased risk of developing rhabdomyolysis and renal failure (against the background of severe acute infection, hypotension, planned major surgery, trauma, severe metabolic disorders). Cancellation of lipid-lowering drugs during pregnancy does not have a significant impact on the results of long-term treatment of primary hypercholesterolemia. Due to the fact that HMG-CoA reductase inhibitors inhibit cholesterol synthesis, and cholesterol and other products of its synthesis play a significant role in fetal development, including the synthesis of steroids and cell membranes, simvastatin can have an adverse effect on the fetus when prescribing pregnant women (women of reproductive age should avoid conception).If a pregnancy occurs during the treatment, the drug should be canceled and the woman warned of a possible danger to the fetus. Simvastatin is not recommended for women of childbearing age who do not use contraceptives. In patients with reduced thyroid function (hypothyroidism) or in the presence of certain diseases kidney disease (nephrotic syndrome) with an increase in cholesterol levels, you should first treat the underlying disease. Simvastatin is prescribed with caution to people who are consume alcohol and / or have a history of liver disease. Before and during treatment, the patient must be on a cholesterol diet. Taking grapefruit juice at the same time may increase the severity of side effects associated with taking Simvastatin, so you should avoid taking them at the same time. Simvastatin is not shown in cases where there is hypertriglyceridemia I, IV and V types. Treatment with Simvastatin can cause myopathy, leading to rhabdomyolysis and renal failure. The risk of this pathology increases in patients receiving one or more of the following drugs simultaneously with Simvastatin: fibrates (gemfibrozil, fenofibrate), cyclosporine, nefazadone, macrolides (erythromycin, clarithromycin), antifungal agents from the group of azoles (ketoconazole, itraconazole) and HIV proteases (ritonavir). The risk of myopathy is also increased in patients with severe renal failure. All patients who start Simvastatin therapy, as well as patients who need to increase the dose of the drug, should be warned about the possibility of myopathy and the need for immediate treatment to the doctor in case of unexplained pain, pain muscle weakness or muscle weakness, especially if accompanied by malaise or fever. Drug therapy should be immediately discontinued if myopathy is diagnosed or assumed. In order to diagnose the development of myopathy, it is recommended to regularly measure CPK values. When treating with Simvastatin, the serum CPK level may increase, which should be taken into account when differentiating for chest pain.The criterion for the abolition of the drug is an increase in the content of CK in the serum of more than 10 times relative to the upper limits of the norm. In patients with myalgia, myasthenia and / or a pronounced increase in the activity of CPK, treatment with the drug is stopped. The drug is effective both as monotherapy and in combination with bile acid sequestrants. If you miss the current dose, you must take the drug as soon as possible. If the next dose comes, do not double the dose. For patients with severe renal insufficiency, the treatment is carried out under the control of the kidney function. The duration of use of the drug is determined individually by the attending physician. The effect on the ability to drive vehicles and control mechanisms. not reported.