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Description
Simgal pills - a lipid-lowering drug that lowers total cholesterol.
Release form
Pills
Composition
Simvastatin \ 000920 mg. Excipients: ascorbic acid, butylhydroxyanisol, citric acid monohydrate, microcrystalline cellulose, pregelatinized starch, magnesium stearate, lactose monohydrate. The composition of the shell: opadry (polyvinyl alcohol, titanium dioxide, purified talc, lecithin, xanthan gum, iron oxide red, iron oxide yellow, indigo carmine varnish).
Pharmacological effect
Lipid-lowering drug, inhibitor of HMG-CoA reductase, obtained synthetically from the fermentation product Aspergillus terreus. Is inactive lactone, in the body undergoes hydrolysis with the formation of hydroxy acid derivative. The active metabolite inhibits HMG-CoA reductase, an enzyme that catalyzes the initial formation of mevalonate from HMG-CoA. Since the transformation of HMG-CoA into mevalonat is an early stage in the synthesis of cholesterol (Xc), 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 processes of synthesis in the body. It causes a decrease in plasma levels of TG, LDL, VLDL and total Xc (in cases of heterozygous familial and non-familial forms of hypercholesterolemia, in mixed hyperlipidemia, when elevated cholesterol is a risk factor). Increases the content of HDL and reduces the ratio of LDL / HDL and total HCF / HDL. The beginning of the manifestation of the effect - after 2 weeks from the start of the reception, the maximum therapeutic effect is achieved after 4-6 weeks. The effect persists with continued treatment, with the cessation of therapy, the content of Xc gradually returns to its original level.
Pharmacokinetics
Absorption Simvastatin absorption is high. Cmax is achieved in 1.3-2.4 hours after ingestion and decreases by 90% in 12 hours. It is subject to the effect of "first passage" through the liver. Distribution and metabolism Binding to plasma proteins is about 95%. Simvastatin is metabolized in the liver by hydrolysis to form pharmacologically active beta hydroxymetabolites. Other active and inactive metabolites are also formed.Withdrawal of T1 / 2 active metabolites is 1.9 hours. It is mainly excreted with feces (about 60%), about 10-15% is excreted by the kidneys as inactive metabolites.
Indications
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 coronary atherosclerosis, combined hypercholesterolemia and hypertriglyceridemia, and, in case of a woman, do not apply to a woman, and do not apply to a woman, in combination with hearth, choleterol and other non-drug measures (exercise and weight loss) . IHD: prevention of myocardial infarction, reducing the risk of death, slowing the progression of atherosclerosis, reducing the risk of revascularization procedures. Cerebrovascular disease: stroke or transient ischemic disorders.
Contraindications
Contraindications: liver disease in the active phase, persistent increase in liver enzymes of unknown etiology, skeletal muscle disease (myopathy), - pregnancy, lactation (breastfeeding), children and adolescents under 18 years of age (efficacy and safety not established), increased sensitivity to simvastatin and other components of the drug (including hereditary intolerance to lactose), as well as to other drugs of the statin series (HMG-CoA reductase inhibitors) in the anamnesis.
Precautionary measures
With caution, the drug is prescribed to patients who abuse alcohol, patients after organ transplantation, who are treated with immunosuppressants (due to an increased risk of rhabdomyolysis and renal failure), in conditions that may lead to the development of severe renal failure, such as arterial hypotension, acute severe infectious diseases.
Use during pregnancy and lactation
Contraindicated
Dosage and administration
The drug should be taken 1 time per day, in the evening, before meals or during meals. The therapeutic effect of Simgal comes in approximately 2 weeks, and the maximum effect is achieved in 4-6 weeks from the start of treatment. Doses and duration of treatment are set individually. With hypercholesterolemia, 10 mg is prescribed 1 time per day in the evening, with IHD, the initial dose of the drug is 20 mg.If necessary, increase the dose at intervals of 4 weeks. The maximum daily dose is 80 mg. When using the drug against the background of immunosuppressive therapy in patients receiving cyclosporine, fibrates, nicotinic acid together with Simgal, the recommended initial dose is 5 mg / day. The maximum daily dose is 10 mg. When using the drug in patients with renal insufficiency, mild and moderate severity of the dosage regimen correction is not required, since simvastatin is eliminated by the kidneys to a small extent. With severe renal failure (CC less than 30 ml / min), treatment begins with a dose of no more than 10 mg / day. Careful medical monitoring of the condition of this category of patients throughout the entire period of treatment is necessary.
Side effects
When applying the recommended therapeutic doses, the drug Simgal is generally well tolerated. On the part of the digestive system: possible nausea, vomiting, abdominal pain, constipation, diarrhea, pancreatitis, flatulence, hepatitis, increased activity of hepatic transaminases, alkaline phosphatase, CK. On the part of the central nervous system and peripheral nervous system: asthenic syndrome, headache, dizziness, insomnia, convulsions, paresthesias, peripheral neuropathy, blurred vision, disturbed taste sensations. On the part of the musculoskeletal system: myopathy, muscle cramps, myalgia, weakness, rarely - rhabdomyolysis. Urinary system: acute renal failure (due to rhabdomyolysis). From the hematopoietic system: thrombocytopenia, anemia. Allergic reactions: angioedema, rheumatic polymyalgia, vasculitis, arthritis, urticaria, skin flushing, lupus-like syndrome, fever, increased ESR, eosinophilia. Dermatological reactions: photosensitivity, skin rash, pruritus, alopecia, dermatomyositis. Other: hot flashes, shortness of breath, palpitations, decreased potency.
Interaction with other drugs
Cytostatics, antifungal agents (ketoconazole, itraconazole), fibrates, high doses of nicotinic acid, immunosuppressants, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone increase the risk of myopathy. The risk of myopathy / rhabdomyolysis increases with the joint appointment of cyclosporine or danazol with high doses of simvastatin.The risk of myopathy increases with the joint appointment of other lipid-lowering drugs (gemfibrozil and other fibrates / except fenofibrate /, as well as nicotinic acid at a dose of? 1 g), which are not potent inhibitors of CYP3A4, but can cause myopathy in monotherapy. The risk of myopathy is increased when co-administering amiodarone or verapamil with high doses of simvastatin. The risk of myopathy is slightly increased in patients receiving diltiazem simultaneously with simvastatin at a dose of 80 mg.
special instructions
At the beginning of therapy with Simgal, a transient increase in liver enzymes is possible. Therefore, before starting therapy and then regularly conduct a study of liver function (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), and also with increasing doses should perform a test to determine the function of the liver. If you increase the dose to 80 mg, you need to test every 3 months. With a persistent increase in transaminase activity (more than 3 times compared with the initial level), the administration of Simgal should be stopped. Simgal, like other HMG-Co-A-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 hypolipidemic drugs during pregnancy has no significant effect 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 the development of the fetus, including the synthesis of steroids and cell membranes, simvastatin can have an adverse effect on the fetus when prescribing it to pregnant women (women reproductive age should avoid conception). If pregnancy occurs during treatment, the drug should be canceled and the woman warned of the possible danger to the fetus. The use of the drug Simgal is not recommended in women of childbearing age who do not use contraceptives.In patients with low thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome), with an increase in cholesterol level, the main disease should be treated first. Simgal is prescribed with caution to persons who abuse alcohol and / or have a history of liver disease. Before and during treatment, the patient should be on a cholesterol diet. The simultaneous intake of grapefruit juice can increase the severity of side effects associated with the administration of the drug Simgal, so their simultaneous administration should be avoided. The preparation Simgal is not indicated in cases where there is hypertriglyceridemia I, IV and V types.