Active metabolite inhibits reductase ), an enzyme that catalyzes the initial reaction of mevalonate . Since the conversion to mevalonate is an early step in cholesterol synthesis, the use of simvastatin does not cause accumulation in the body is potentially toxic sterols. Is easily metabolized to acetyl-CoA, which is involved in many processes of synthesis in the body. It is a decrease in blood plasma triglycerides, low density lipoprotein very low density lipoproteins and total cholesterol (in cases . heterozygous familial and non-familial forms of hypercholesterolemia, with mixed hyperlipidemia when elevated cholesterol is a risk factor) increases the content of high density lipoprotein primobolan acetate cholesterol and decreases the ratio and total ratio. onset of effect – 2 weeks from the start of the reception , the maximum therapeutic effect is achieved within 4-6 weeks. Action is maintained with continued treatment, at the termination of therapy cholesterol gradually returned to baseline.
Absorption of simvastatin high. After oral administration the maximum plasma concentration is reached after about 1,3-2,4 hours, and reduced by 90% after 12 hours. Communication to plasma proteins is approximately 95%.
It is metabolized in the liver, it has the effect of “first pass” through the liver (hydrolyzed to form an active derivative: a beta – hydroxy acid, found and other active and inactive metabolites). The half-life of the active metabolite is 1.9 hours.
Excreted mainly with faeces (60%) in the form of metabolites. Approximately 10-15% is excreted by the kidneys in an inactive form.
Indications Hypercholesterolemia :
- Primary Hypercholesterolemia (type IIa and IIb), when poor diet low in cholesterol and other non-drug interventions (exercise and weight reduction) in patients with an increased risk of coronary atherosclerosis;
- combined hypercholesterolemia and hypertriglyceridemia, is not correctable special diet and exercise.
Coronary heart disease :
for the prevention of myocardial infarction, to primobolan acetate reduce the risk of death, reducing the risk of cardiovascular events (stroke or transient ischemic attacks), slowing the progression of atherosclerosis of the coronary vessels, reducing the risk of revascularization procedures.
- Hypersensitivity to simvastatin or to other components of the preparation (including hereditary lactose intolerance), as well as several other statin drugs (HMG-CoA reductase) in history;
- liver disease in the active phase, a persistent increase in activity of “liver” enzymes of unknown etiology;
- diseases of skeletal muscles (myopathy);
- age of 18 years (effectiveness and safety have been established).
Be wary appoint patients who abuse alcohol, transplant patients undergoing immunosuppressive therapy (due to an increased risk of rhabdomyolysis and renal failure); in conditions that can lead to severe renal insufficiency, such as hypotension, acute infectious diseases heavy currents expressed metabolic and endocrine disorders, disorders of water balance -elektrolitnogo, surgery (including dental), or injury;patients with low or high tone of the skeletal muscles of unknown etiology; epilepsy, liver disease history.
Pregnancy and lactation
Primobolan acetate is contraindicated in pregnant women. There are several reports of malformations in newborns whose mothers took simvastatin. Women of childbearing age who take simvastatin should avoid conception. If during treatment pregnancy yet occurred, should be abolished, and the woman should be advised of the potential hazard to the fetus. Data on the allocation of simvastatin in breast milk are not available. The appointment during lactation should be borne in mind that many drugs are excreted in breast milk, and there is a threat of severe reactions, so breast-feeding during treatment is not recommended.
The time of the drug should not be linked with the meal. The recommended dose for the treatment of hypercholesterolemia varies from 10 to 80 mg 1 time per day in the evening. The recommended starting dose for patients with hypercholesterolemia is 10 mg. The maximum daily dose -. 80 mg changes (selection) the dose should be performed at intervals of 4 weeks . In most patients, the optimal effect is achieved by taking the drug at doses up to 20 mg per day. In patients with homozygous familial hypercholesterolemia recommended daily dose is 40 mg 1 time per day in the evening or 80 mg in three divided doses (20 mg in the morning, 20 mg day and 40 mg in the evening). in the treatment of patients with coronary heart disease (CHD) or at high risk , effective are 20-40 mg per day. Therefore, the recommended initial dose in these patients – 20 mg per day. Change (selection) of the dose should be performed at intervals of 4 weeks, if necessary dose can be increased to 40 mg per day. If the content of less than 75 mg / dl (1.94 mmol / l), total cholesterol – less than 140 mg / dl (3.6 mmol / L), the dose should be reduced. In elderly patients and in patients with mild or moderate degree of renal failure dosage changes drug is not required. in patients with chronic renal failure (creatinine clearance less than 30 mL / min) or receiving cyclosporin, danazol, gemfibrozil or other fibrates (except fenofibrate), nicotinic acid lipid-lowering doses ( > 1 g / day) in combination with simvastatin, the maximum recommended dosage of simvastatin should not exceed 10 mg per day. in patients taking amiodarone or verapamil simultaneously should not exceed 20 mg.