Index of drugs

Treatment of primary or mixed dyslipidemia as a dietary supplement, when the response to dietary treatment and other non-pharmacological treatments (eg physical exercise, weight loss) is insufficient. Treatment of homozygous familial hypercholesterolaemia as a dietary supplement and other lipid-lowering treatments (eg LDL-aresis) or when such methods are inappropriate. Reducing the incidence and mortality of cardiovascular diseases in patients with overt cardiac atherosclerosis or diabetes, with normal or elevated total cholesterol, as adjunctive therapy to correct other risk factors, and to supplement other treatments to prevent cardiovascular disease.

1 tabl powl. contains 20 mg or 40 mg of Simvastatin (and 131.46 mg or 262.92 mg lactose, respectively).

The active metabolite of simvastatin (beta-hydroxy acid) is an inhibitor of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMG-CoA). Inhibition of the production of this enzyme reduces the synthesis of cholesterol at the level of HMG-CoA conversion to mevalonate. Simvastatin also induces the LDL receptor, which leads to increased LDL-cholesterol catabolism. Simvastatin reduces total blood cholesterol, LDL and VLDL and triglycerides, and also causes a small increase in HDL-cholesterol. There is also a significant reduction in the concentration of apolipoprotein B. Simvastatin is well absorbed from the gastrointestinal tract, the food does not affect the absorption. A significant uptake is in the liver (first-pass effect). Less than 5% of the dose is circulating as an active metabolite. The maximum concentration of the active inhibitor in the plasma is reached about 1-2 hours after administration. 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 the active substance or to any of the excipients. Active liver disease or persistent, unexplained elevation of blood transaminases. Concomitant use of strong CYP3A4 inhibitors (drugs that increase simvastatin AUC approximately 5-fold or more) such as Itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors (eg nelfinavir), boceprevir, telaprevir, Erythromycin, Clarithromycin, telithromycin and nefazodone. Co-administration of gemfibrozil, cyclosporin or danazol. Pregnancy. Breastfeeding period.

Carefully use in patients with predisposing factors for rhabdomyolysis: in elderly patients (over 65 years of age), with impaired renal function, with refractory or untreated hypothyroidism, with hereditary disorders of the muscular system in the past (also family history) in patients who have experienced muscle or alcohol abuse in the past with statins or fibrates. 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, do not start treatment. Use with caution in patients with diabetes and hepatic impairment. Treatment should be discontinued a few days before the planned major surgery or if it is necessary to undergo internist or surgical treatment.

Do not use in pregnant women, those planning pregnancy or those who are suspected of being pregnant, as mother's treatment with simvastatin may reduce the fetus concentration of mevalonate, which is a precursor to cholesterol biosynthesis. It is not known whether simvastatin or its metabolites are excreted in human milk - do not use during breast-feeding due to the possibility of serious side effects in the infant.

Rare: anemia, headache, paresthesia, dizziness, peripheral neuropathy, constipation, abdominal pain, bloating, indigestion, diarrhea, nausea, vomiting, pancreatitis, hepatitis, jaundice, rash, pruritus, alopecia, myopathy - more often after 80 mg (including myositis), rhabdomyolysis (with or without acute renal failure), muscle pain, muscle spasms, weakness, symptoms of hypersensitivity syndrome (angioneurotic edema, lupus-like syndrome, rheumatoid type muscle pain, dermatomyositis, vasculitis, thrombocytopenia , eosinophilia, accelerated OB, arthritis, arthralgia, urticaria, hypersensitivity to light, fever, redness, difficulty in breathing, malaise), increase in blood transaminases (ALT, AST, GGT), increase in ALP, increase in CK in blood. Very rare: insomnia, impaired memory, liver failure (fatal and fatal). Frequency unknown: depression, interstitial lung disease, tendinopathy (sometimes complicated by tendon rupture), tendon rupture, erectile dysfunction. Patients taking statins, including Simvastatin, have reported increases in HbA1c and fasting blood glucose. Rare cases of cognitive dysfunctions have also been observed (eg memory loss, poor memory, amnesia, memory impairment, confusion) in patients receiving statins, including simvastatin; the reporting disorders were generally mild and resolved after discontinuation of statin therapy; a variable time to onset (from 1 day to several years) and resolution of symptoms (median 3 weeks) were observed. Side effects characteristic of statins: sleep disorders (including nightmares), sexual dysfunction, diabetes (frequency depends on the presence or absence of risk factors, i.e. fasting blood Glucose ≥ 5,6 mmol / l, BMI> 30 kg / m2, increased triglycerides, history of hypertension). The long-term effect of simvastatin is not known for the physical and intellectual development and sexual maturation of children and adolescents.

Orally.The dose range is 5-80 mg / day. If necessary, the dose should be adjusted at intervals of at least 4 weeks to a maximum of 80 mg / day. A dose of 80 mg per day is only recommended for patients with severe hypercholesterolaemia and a high risk of cardiovascular complications who have not achieved the goals of treatment with a lower dose. The patient should use a standard low-cholesterol diet, which should be continued during treatment.hypercholesterolemia10-20 mg once a day; if it is necessary to reduce the LDL-cholesterol> 45%, the initial dose may be 20-40 mg once a day.Homozygous familial hypercholesterolaemia: 40 mg once a day.Prevention of cardiovascular diseases20-40 mg once a day.Combination treatment with other medicines: simvastatin should be taken not less than 2 hours before or not less than 4 hours after administration of bile acid sequestrants. In the case of simultaneous treatment with fibrates (except gemfibrozil - contraindicated or fenofibrate) the simvastatin dose can not be> 10 mg / day. Patients taking simvastatin concomitantly with Amiodarone, Verapamil, diltiazem or Amlodipine must not receive simvastatin> 20 mg / day.Special groups of patients. In patients with severe renal impairment (CCr <30 ml / min), simvastatin> 10 mg / day should be carefully considered and, if necessary, very cautiously start treatment. No dosage adjustment is necessary in patients with mild or moderate renal impairment or in elderly patients.Children and teenagers 10-17 years (boys ≥12 on the Tanner scale and girls at least one year from the first menstruation) with heterozygous familial hypercholesterolaemia: the recommended starting dose is 10 mg per day. The recommended dose range is 10-40 mg / day. The largest recommended dose is 40 mg per day. Doses should be adjusted individually according to the recommended goal of therapy according to the recommendations for treatment of children and adolescents. The dose should be adjusted at intervals of at least 4 weeks. The appropriate diet should be used. There is limited experience in the use of simvastatin in pre-pubertal children.Way of giving. The drug should be taken once a day, in the evening. The tablets can be divided into equal doses.