Hyperlipidaemia - the preparation is indicated as a supplementary dietary treatment for patients with primary hypercholesterolemia, heterozygous familial hypercholesterolemia and mixed hyperlipidemia, in which the response to diet and other non-pharmacological methods is insufficient. Coronary disease - the preparation is indicated in patients with coronary disease and hypercholesterolemia in order to: reduce the risk of death due to coronary artery disease, reduce the risk of non-fatal infarction, reduce the need for coronary revascularization procedures.
Composition:
1 tabl powl. contains 20 mg or 40 mg of simvastatin.
Action:
HMG-CoA reductase inhibitor that catalyzes the conversion of HMG-CoA to mevalonate and is the most important enzyme affecting the rate of cholesterol synthesis. Simvastatin after absorption in the gastrointestinal tract easily hydrolyses into the ß-hydroxylic acid, which is a strong competitive inhibitor of HMG-CoA reductase, resulting in decreased cholesterol synthesis. Inhibition of cholesterol synthesis in the liver leads to an increase in the number of LDL receptors and accelerates catabolism of LDL. There may also be a reduction in LDL production due to inhibition of hepatic VLDL lipoprotein synthesis. Simvastatin reduces total cholesterol, LDL-cholesterol and triglycerides by 25%, 35% and 10%, respectively. At the same time, it increases cholesterol-HDL by 12%. There is also a reduction in the concentration of apolipoprotein B. After absorption from the gastrointestinal tract, simvastatin is rapidly metabolised in the liver (the so-called first-pass effect), as a result of which the availability of the drug in the general circulation is small and variable. Less than 5% of the oral dose enters the circulation as an active metabolite. It is highly bound to plasma proteins (95%). The time to reach the maximum concentration is 1.3-2.4 hours. Simvastatin is hydrolysed to the active form of ß-hydroxylic acid in the liver. Three other metabolites have also been isolated. Simvastatin is mainly excreted in the faeces, where the non-absorbed fraction of the drug occurs, in the amount of 60% of the administered dose. About 13% of the drug is excreted in the urine. T0,5 the active metabolite is about 2 hours.
Contraindications:
Hypersensitivity to simvastatin or other ingredients of the preparation. Active liver disease or unexplained and persistent increase in blood transaminases. Pregnancy and breastfeeding period and women of childbearing potential not using effective methods of contraception. Simultaneous use with mibefradil.
Precautions:
Treatment with simvastatin should be temporarily suspended or terminated in patients who have risk factors predisposing to renal failure secondary to rhabdomyolysis, e.g. in patients with severe infection, hypotension, undergoing major surgery, injuries, patients with severe electrolyte disturbances, activities of the endocrine system or convulsive seizures. The indication for discontinuation of treatment is: diagnosis or suspicion of myopathy, finding increased creatine kinase (10-fold in relation to the norm), increase in blood transaminases (3-fold in relation to the norm). Before taking medicines that may interact with simvastatin (CYP3A4 inhibitors), potential benefits and risks should be considered. The drug should be used with caution in patients who consume significant amounts of alcohol and / or have had liver disease. The safety and efficacy of the medicine in children has not been documented.
Pregnancy and lactation:
Safety in pregnancy - cat. X. The drug is contraindicated during pregnancy and breastfeeding. At least one month should be allowed between the end of the HMG-CoA reductase inhibitor and the intended pregnancy. Women of childbearing age must use effective contraception.
Side effects:
Musculoskeletal system: muscle cramps, muscle pain, joint pain.Nervous system: abnormalities of some cranial nerves (including taste disorders, disturbances of movements not controlled by eyesight, facial nerve paralysis), tremors, dizziness, memory loss, hyperaesthesia, peripheral neuropathy, peripheral nerve palsy, mental disorders, anxiety, insomnia, depression. Digestive system: pancreatitis, hepatitis (including chronic active hepatitis), congestive jaundice, hepatic steatosis, in rare cases cirrhosis, fulminant hepatic necrosis and hepatocellular carcinoma; anorexia, vomiting. Skin: alopecia, pruritus, skin changes (nodules, discoloration, dry skin and mucous membranes, changes in hair and nails). Gynecomastia, loss of libido, erectile dysfunction. Progression of cataracts, paralysis of the eye muscles. Simvastatin and other HMG-CoA reductase inhibitors may occasionally induce myopathy with muscle pain and weakness, which is accompanied by a significant increase in creatine kinase (CK) - more than 10 times. The incidence and severity of myopathy is increased when co-administered with fibrates or nicotinic acid and concomitant use of CYP3A4 isoenzymes. Rare cases of myoglobinuria following rhabdomyolysis have been described, with or without acute renal failure. In rare cases, symptoms of hypersensitivity syndrome have been reported. Changes in the results of laboratory tests: increase in transaminases, alkaline phosphatase, gamma-glutamyl-transpeptidase and increase in bilirubin; thyroid dysfunction.
Dosage:
Orally, once in the evening. Hyperlipidaemia: the recommended one-time daily dose is 5-20 mg. The daily dosage range is 5-40 mg. Dose changes should be made at intervals of at least 4 weeks. The maximum recommended daily dose is 40 mg. The maximum effectiveness occurs after 4-6 weeks of treatment. If the cholesterol-LDL level drops below 1.94 mmol / l or total cholesterol below 3.6 mmol / l, a dose reduction should be considered. Coronary heart disease: usually 20 mg daily is used; if necessary, dose selection is carried out as described above. Elderly patients have a reduction in cholesterol after 20 mg or less. In patients receiving concomitant cyclosporine, the starting dose of 5 mg simvastatin should be used and the 10 mg dose should not be exceeded. For patients receiving fibrates at the same time, the maximum dose of simvastatin is 10 mg per day. In patients with renal insufficiency with a creatinine clearance below 30 ml / min, treatment should be started with 5 mg daily and doses higher than 10 mg per day can be used exceptionally.
(C)
