After oral administration of simvastatin, which is an inactive lactone, is hydrolyzed to give the corresponding beta-hydroxy-acid derivative, which is the major metabolite and possesses high inhibitory activity against reductase, the enzyme that oral primobolan catalyzes the initial and most significant step of cholesterol biosynthesis. Clinical studies have demonstrated the effectiveness of Zocor in reducing the levels of total cholesterol in the blood plasma, low density lipoprotein.
The 5-year multicenter, randomized, double-blind, placebo-controlled study to protect the heart (Heart Protection Study – HPS) the effectiveness of Zocor therapy has been demonstrated in 20 536 patients with hyperlipidemia or not, are at high risk of coronary heart disease due to the presence of diabetes mellitus , stroke and other vascular diseases.
In this study, Zocor 40 mg per day reduced total mortality by 13% compared with placebo, the risk of death associated with coronary artery disease by 18%, the risk of major coronary events (nonfatal myocardial infarction or death associated with coronary heart disease) 27 %, the risk of the need for surgical procedures to restore coronary blood flow (aorto-coronary bypass and percutaneous transluminal angioplasty) by 30%, the risk of the need for recovery of peripheral blood flow and other non-coronary revascularization by 16%, the risk of stroke by 25%. The frequency of hospitalizations for heart failure was reduced by 17%. The risk of major coronary and vascular events was reduced by 25% in patients with CHD or without, including patients with diabetes, peripheral vascular disease and cerebrovascular disease. In patients with diabetes, Zocor to 21% reduced risk of developing cardiovascular complications, including operations to restore the peripheral blood flow, amputation of the lower extremities and the occurrence of venous ulcers.
In another multicentre, placebo-controlled study involving 404 patients. Zokora according to coronary angiography slowed the progression of coronary atherosclerosis and the emergence of new sectors like atherosclerosis and new total occlusion, whereas in patients treated with standard therapy, there was a steady progression of coronary artery atherosclerosis.
Metabolism. The major active metabolites of simvastatin in the blood plasma are betagidroksiatsid oral primobolan and 6 “hydroxy, 6” hydroxymethyl and 6 “-eksometilen derivatives. The maximum concentration of metabolites of simvastatin in plasma achieved through 1,3-2,4 hours after a single dose. There information about reaching the maximum concentration of simvastatin and its metabolites in the period up to 4 hours and its slow decline over 12 hours at about 10%. upon receipt of simvastatin in recommended therapeutic doses (5-80 mg per day) remains linear profile AUG (area under the curve concentration – time) of the active metabolite in the general circulation.
The linear dependence is maintained with increasing dose up to 120 mg. Simvastatin is an inactive lactone, which is readily hydrolyzed in developing B-hydroxy acid, L-654,969, a potent inhibitor of HMG-CoA reductase. The plasma metabolite represented by L-654,969 and 4 active metabolite. Inhibition of HMG-CoA reductase is the basis of all the metabolites in pharmacokinetic studies hydroxy acids (active inhibitors). Both are determined in plasma when assigning simvastatin.
Suction is exposed for about 85% of an oral dose of simvastatin.
Distribution. After intake in the liver determined simvastatin higher concentration than in other tissues. The content of the active form of simvastatin L-654,969 in the systemic circulation is less than 5% of an oral dose, 95% of this amount is bound to proteins condition. Simvastatin resulted active in liver metabolism (more than 60% in men) is its low content in the general circulation. The ability to penetrate the blood-brain barrier is simvastatin and the blood-barrier has not been studied.
Withdrawal. The first passage through the liver blood flow simvastatin is metabolized, followed by excretion of the drug and its metabolites in the bile. In a study of 100 mg of drug administered in capsules (5 x 20 mg) simvastatin labeled C14 accumulates in the blood, urine and feces. About 60% of the labeled product was detected in the stool and about 13% of all – in urine. AUC coefficient of variation in the general circulation does not depend on the dose of simvastatin. In this study, patients received oral doses of simvastatin tablets in 5, 10, 20, 60, 90 and 120 mg. Eating (within a standard hypolipidemic diet) immediately after receiving simvastatin does not violate the pharmacokinetic profile of the drug. Pharmacokinetic parameters when receiving a single dose and long-term treatment with simvastatin suggest that simvastatin does not accumulate in the tissues with prolonged treatment. Maximum plasma concentration achieved within inhibitors 1,3-2,4 hours after ingestion. In a study of patients with severe renal failure (kratinina clearance less than 30 mL / min) after administration of a single dose plasma HMG-CoA reductase inhibitor drug concentration was approximately 2-fold higher than in healthy volunteers.
Coronary heart disease (CHD) or at high risk for coronary heart disease:
In patients with a high risk of CHD (in the presence of hyperlipidemia or without it), for example, in patients with diabetes, patients with stroke or other cerebrovascular disease in history, in patients with peripheral vascular disease, or in patients with coronary artery disease or predisposition to coronary artery oral primobolan disease Zokora FORTE is indicated for:
- Reducing the risk of total mortality by reducing CHD deaths as a result;
- Reduce the risk of serious cardiovascular and coronary events
- nonfatal myocardial infarction
- coronary death
- revascularization surgery;
- Reduce the risk of the need for operations to restore coronary blood flow (such as coronary artery bypass grafting and percutaneous transluminal coronary angioplasty);
- Reduce the risk of the need for surgery to restore blood flow in peripheral and other non-coronary revascularization;
- Reduce the risk of hospitalization due to angina.
- If the use of diet and other non-drug treatment is not enough, Zokora FORTE assigned together with diet to:
- reducing elevated total cholesterol, LDL cholesterol, triglycerides, apolipoprotein B (apo B);
- increase HDL cholesterol in patients with primary hypercholesterolaemia, including heterozygous
- familial hypercholesterolaemia (Pa type hyperlipidemia Fredrickson classification) hypercholesterolemia or mixed (type lib hyperlipidemia Fredrickson classification);
decrease LDL cholesterol / HDL cholesterol and total cholesterol / HDL cholesterol.
- Hypertriglyceridemia (type IV hyperlipidemia Fredrickson classification).
- An adjunct to diet and other methods of treating patients with homozygous familial hypercholesterolemia to reduce elevated total cholesterol, LDL cholesterol, and apolipoprotein B.
- Primary disbetalipoproteinemiya (type III hyperlipidemia Fredrickson classification).
In patients with diabetes, Zocor FORTE reduces the risk of peripheral vascular complications (revascularization operations, lower limb amputations, occurrence of venous ulcers).
In patients with coronary artery disease and hypercholesterolemia Zokora Forte slows the progression of coronary atherosclerosis, including reducing the incidence of new complications.
Hypersensitivity to any component of the drug.
Liver disease in the active phase or persistent elevation of transaminases in the blood plasma of unknown etiology.
Pregnancy and lactation.
Simvastatin, like other inhibitors oral primobolan of HMG-CoA reductase can sometimes cause myopathy.
Many of the patients who underwent treatment during rhabdomyolysis simvastatin had a complicated medical history, including suffered renal failure, usually due to diabetes. Such patients require more careful observation. Therapy with simvastatin should be temporarily discontinued in these patients a few days before the big surgical interventions and in the postoperative period.
Patients with sustained elevated levels of serum transaminases exceeding 3 times the upper limit of normal, the drug should be discontinued.
In severe renal insufficiency (creatinine clearance less than 30 ml / min), should carefully weigh the advisability of the appointment of the drug in doses exceeding 10 mg per day. If such dosages are deemed necessary, they should be administered with caution.
Alcohol abuse before treatment.
Pregnancy and lactation
Zokora FORTE is contraindicated in pregnant women. Since safety in pregnant women has not been proven, and there is no evidence that treatment with the drug during pregnancy brings obvious benefits, the drug should be discontinued if pregnancy occurs. Simvastatin should be administered to women of childbearing age only when the probability of pregnancy is very small.
If during treatment with Zocor FORTE pregnancy occurs, the drug should be discontinued, and the woman warned of the possible danger to the fetus. Data on the allocation of simvastatin and its metabolites in breast milk are not available. The appointment Zokora FORTE women during lactation should be borne in mind that many drugs are excreted in breast milk, and there is a threat of serious adverse reactions, so breast-feeding is not recommended.
APPLICATION IN PEDIATRIC PRACTICE
Data on the efficacy and safety of children is not enough, therefore the use in children is not recommended.
DOSAGE AND ADMINISTRATION
BEFORE treatment with drugs Zocor FORTE Patients should be given a standard hypolipidemic diet, which must be observed during the entire course of treatment.
The recommended dose of Zocor – from 5 to 80 mg should be taken once daily in the evening. When selecting a dose of Zocor its change should be made at intervals of not less than 4 weeks, to a maximum daily dose of 80 mg once daily in the evening.
Patients with coronary heart disease (CHD) or at high risk of developing coronary heart disease
Standard starting Zocor dose for patients at high risk for coronary heart disease in combination with hyperlipidemia or without it (if you have diabetes, stroke or other cerebrovascular disease in the history of peripheral diseases vascular, ischemic heart disease) is 40 mg once a day in the evening. Drug therapy can be administered simultaneously with diet and exercise therapy.
Patients with hypercholesterolemia, without the above risk factors
Standard Zocor initial dose is 20 mg once a day in the evening. For patients who need a significant (more than 45%) reduction in LDL cholesterol level, the initial dose may be 40 mg once a day in the evening. Patients with mild to moderate hypercholesterolemia Zocor therapy can be initiated with a dose of 10 mg once daily. If necessary, the selection of doses should be carried out in accordance with the above scheme (see. “DOSAGE AND ADMINISTRATION / coronary heart disease” section).
Patients with homozygous familial hypercholesterolemia
recommended dose Zocor is 40 mg once a day in the evening, or 80 mg per day in 3 doses: 20 mg in the morning, afternoon, and 20 mg to 40 mg in the evening. In such patients, Zocor is used in combination with other treatments that reduce the level of cholesterol (e.g., LDL apheresis) or without them, if they are unavailable.
Zocor FORTE may be administered 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 of niacin (> 1 g / day) in combination with simvastatin, the maximum recommended dose is 10 mg of Zocor per day. For patients taking amiodarone or verapamil together with Zocor, the daily dose of Zocor should not exceed 20 mg (see. Sections “SPECIAL INSTRUCTIONS / myopathy / rhabdomyolysis” and “Interaction with other medicines”).
In renal insufficiency
Since Zocor FORTE excreted by the kidneys in a small amount, no need to change the dose in patients with moderate renal failure. In patients with severe renal impairment (creatinine clearance less than 30 mL / min) should carefully weigh the desirability drug administration at doses exceeding 10 mg per day. If such dosages are deemed necessary, the drug should be used with caution. (see. “With cautious” section) Buy muscle labs usa online