Index of drugs

Hypercholesterolemia. Treatment of primary hypercholesterolemia or mixed hyperlipidemia, as a diet supplement, when the response to diet or other nonpharmacological treatment (eg physical exercise, weight loss) is insufficient. Treatment of familial homozygous hypercholesterolemia as a supplement to diet and other lipid-lowering therapy (eg LDL apheresis) or if such treatment is inappropriate or unavailable.Prevention of events from the cardiovascular system. Reduction of morbidity and mortality of cardiovascular diseases in patients with overt atherosclerosis or diabetes, with normal or elevated cholesterol, as adjunctive therapy to correct other risk factors or supplement other treatments to prevent heart disease.

1 tabl powl. contains 40 mg of simvastatin. The drug contains lactose.

The active metabolite of Simvastatin (beta-hydroxy acid) is an inhibitor of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMG-CoA). This enzyme catalyzes the conversion of HMG-CoA to mevalonate, i.e. an early reaction and, at the same time, a cholesterol biosynthesis control step. Simvastatin reduces both normal and elevated LDL cholesterol. The mechanism of LDL cholesterol lowering by simvastatin may be a result of both lowering VLDL cholesterol and LDL receptor induction, leading to reduced production and increased catabolism of LDL cholesterol. There is also a significant reduction in apolipoprotein B levels. In addition, simvastatin moderately increases HDL cholesterol and decreases serum triglycerides. After oral administration less than 5% of the dose gets into the systemic circulation as a beta-hydroxy acid. The maximum concentration of active inhibitors in the plasma occurs within approx. 1-2 h after administration. Taking simvastatin with a meal does not affect its absorption. The drug and its metabolites bind to plasma proteins in over 95%. Simvastatin is a substrate for CYP3A4, the major metabolites are: beta-hydroxy acid and 4 other active metabolites. 13% of the dose is excreted in the urine, 60% in the faeces.

Hypersensitivity to simvastatin or other components of the drug. Active liver disease or persistent, unexplained increase in serum transaminases. Pregnancy and breastfeeding. Concomitant administration of potent CYP3A4 inhibitors (eg Itraconazole, ketoconazole, HIV protease inhibitors, Erythromycin, Clarithromycin, telithromycin and nefazodone).

Carefully use and consider the expected benefits of treatment and the associated risk in patients with predisposing factors for rhabdomyolysis: in elderly patients (> 70 years old), with impaired renal function, with refractory or untreated hypothyroidism, with hereditary disorders on the part of the muscular system (also in the family history), in patients with a history of toxic effects of statins or fibrates on the muscles and in patients with alcohol dependence. In these groups of patients, CK activity should be measured before starting treatment - if the CK activity is higher than 5 times the upper limit of normal (ULN), treatment should not be started. Drug administration must be discontinued if the creatine kinase activity increases (more than 5 times above ULN); discontinuation of treatment should be considered if the muscle symptoms are significantly increased even when the CK activity is less than 5 times ULN. If you suspect myopathy for any other reason, the medicine should be discontinued. If the muscle symptoms go away and the CK values ​​return to normal, re-administration of the statin at the lowest effective dose may be considered with close monitoring of the patient's state of health. Treatment should be discontinued a few days before the planned major surgery or if it is necessary to undergo internist or surgical treatment.Special care should be taken in patients who have increased serum aminotransferases - these patients should be restarted without delay and should be repeated more frequently. The drug should be discontinued if persistent elevation of transaminases persists, especially if it reaches 3 times ULN and persists. It is recommended that liver function tests be carried out in all patients prior to initiation of therapy and then, when clinically indicated. Patients who require simvastatin 80 mg should be given an additional test prior to a change in dosage, 3 months after changing the dose to 80 mg, and then from time to time in the first year of treatment. In patients treated with coumarin derivatives, the prothrombin time should be determined prior to initiating simvastatin therapy and often repeated at the beginning of therapy, when the dose is changed and when the preparation is discontinued. After stable prothrombin time values ​​are achieved, measurements can be made at intervals recommended for patients treated with coumarin. The drug should be used with caution in people who consume significant amounts of alcohol. The drug is not recommended for use in children and adolescents. The drug contains lactose - should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.

Do not use during pregnancy or in women who are planning to become pregnant in the near future or those who are suspected of being pregnant. Treatment should be stopped during pregnancy or until the patient is pregnant. It is not known whether simvastatin or its metabolites are excreted in human milk. Women taking the drug should not breastfeed because of the possibility of serious side effects in the child.

Rare: anemia; headache, paresthesia, dizziness, peripheral neuropathy; constipation, abdominal pain, flatulence, indigestion, diarrhea, nausea, vomiting, pancreatitis; hepatitis / jaundice; rash, pruritus, baldness; myopathy, rhabdomyolysis, muscle pain, muscle cramps; asthenia. In rare cases, symptoms of hypersensitivity syndrome with one or more of the following symptoms have been reported, such as: angioneurotic edema, lupus-like syndrome, rheumatoid-type muscle pain, myositis and dermatitis, vasculitis, thrombocytopenia, eosinophilia, elevated OB, arthritis, arthralgia , urticaria, hypersensitivity to light, fever, hot flushes, shortness of breath, feeling unwell. Effects on the results of laboratory tests - rare: elevation of transaminases (alanine aminotransferase, aspartate aminotransferase, γ-glutamyltranseptidase), elevation of alkaline phosphatase, increased CK activity in serum.

Orally. Adults.hypercholesterolemia: initially 10-20 mg once a day, in the evening; if it is necessary to reduce the LDL cholesterol above 45%, the initial dose may be 20-40 mg once a day, in the evening.Familial homozygous hypercholesterolemiathe recommended dose is 40 mg once a day, in the evening or 80 mg in 3 divided doses (in the morning and at noon after 20 mg, in the evening - 40 mg); drug used as a supplement to other lipid-lowering treatments or if such treatment is not available.Prevention of cardiovascular diseases: 20-40 mg once a day in the evening; treatment should begin with the introduction of diet and exercise.Combination therapy: simvastatin should be taken no more than 2 hours before or no earlier than 4 hours after taking bile acid sequestrants; when combined with ciclosporin, danazol, gemfibrozil, fibrates (except fenofibrate), the dose of coadministered simvastatin should not exceed 10 mg daily; in patients taking Amiodarone or Verapamil, the dose of simvastatin should not exceed 20 mg daily. The maximum daily dose is 80 mg - it is only recommended for patients with severe hypercholesterolemia and high risk of cardiovascular complications. Dose changes should be made at intervals of not less than 4 weeks.In patients with severe renal impairment (creatinine clearance <30 ml / min), simvastatin 10 mg should be considered, should such doses prove necessary, they should be used with extreme caution. No dosage adjustment is necessary for patients with moderate renal insufficiency or elderly patients.