Index of drugs

Treatment of primary hypercholesterolaemia and mixed dyslipidemia, as a supplement to the diet, 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 low-density lipoprotein apoptotic [LDL]) or if such treatment is inappropriate. Reduction of morbidity and mortality of cardiovascular diseases in patients with symptomatic atherosclerosis or diabetes, with normal or elevated cholesterol, as adjunctive therapy to correct other risk factors or to supplement other therapies to prevent heart disease.

1 tabl powl. contains 20 mg or 40 mg simvastatin. The preparation 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. 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 to any of the excipients. Active liver disease or persistent, unexplained increase in serum transaminases. Pregnancy and lactation. Concomitant administration of potent CYP3A4 inhibitors, e.g. Itraconazole, ketoconazole, Fluconazole, posaconazole, HIV protease inhibitors (ie nelfinavir), Erythromycin, Clarithromycin, telithromycin and nefazodone.

Caution in patients with predisposing factors for rhabdomyolysis: in elderly patients (over 70 years), with impaired renal function, uncontrolled hypothyroidism, with hereditary disorders of the muscular system (including family history), in patients in the past administration of statins or fibrates caused toxic effects on the muscles and patients addicted to alcohol. 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. Drug administration must be discontinued if the creatine kinase activity increases (more than 5 times the upper limit of normal); discontinuation of treatment should be considered if the muscle symptoms are exacerbated even if the CK activity is less than 5 times the upper limit of normal. If myopathy is suspected for any reason, the medicine should be discontinued. If the muscle symptoms subside and the CK value returns to normal, re-administration of the same or another statin at the lowest effective dose may be considered with close monitoring of the patient's condition. Treatment should be discontinued a few days before the planned major surgery and if internal or surgical treatment is necessary. Special attention should be paid to patients who have increased serum transaminases.The drug should be discontinued if persistent elevation of aminotransferases persists, especially if it reaches 3 times the upper limit of normal and will persist. The drug should be used with caution in patients who consume significant amounts of alcohol. In patients suspected of having interstitial lung disease, treatment with statins should be discontinued. The safety and efficacy of simvastatin in patients aged 10-17 years with familial homozygous hypercholesterolemia have been evaluated in controlled clinical trials in adolescents: boys on the Tanner scale, phase II and above, and girls at least 1 year after the onset of menarche. Doses greater than 40 mg were not tested in this population. There was no apparent effect on sex growth or puberty in boys and girls nor was there any effect on the length of the menstrual cycle in girls. In patients under 18 years, the safety and efficacy of treatment for> 48 weeks have not been studied and the effects of long-term effects on physical, intellectual and sexual maturation are unknown. Simvastatin has not been studied in patients under 10 years of age or in children prior to puberty and girls before the onset of menarche. The product contains lactose - should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.

The preparation is contraindicated during pregnancy and breastfeeding and in women planning pregnancy.

Rare: anemia, headache and dizziness, paresthesia, peripheral neuropathy, constipation, abdominal pain, bloating, indigestion, diarrhea, nausea, vomiting, pancreatitis, hepatitis / jaundice, rash, pruritus, alopecia, myopathy (also with muscle inflammation), rhabdomyolysis with or without acute renal failure, myalgia, muscle cramps, myositis, polymyositis, asthenia, symptoms of hypersensitivity syndrome (angioneurotic edema, lupus-like syndrome, polyarthritis polyarthritis of the proximal limbs, dermatomyositis, vasculitis, thrombocytopenia, eosinophilia , increased OB, inflammation and pain in the joints, urticaria, hypersensitivity to light, fever, hot flushes, shortness of breath and malaise), increase in transaminases (alanine transferase, aspartate aminotransferase, gamma-glutamyl transpeptidase), increase in alkaline phosphatase, increase in activity CK in the serum. Very rare: insomnia, impaired memory, liver failure, tendon disorders (sometimes rupture). In addition, the following adverse reactions are described for some statins: sleep disorders (including insomnia and nightmares), memory loss, sexual dysfunction, depression, in individual cases, interstitial lung disease, especially during long-term use.

Orally. Adults.hypercholesterolemia: the starting dose is usually 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).Prevention of events from the cardiovascular systemthe recommended dose is 20-40 mg once a day in the evening; treatment should begin with the introduction of diet and exercise.Simultaneous use with other drugs: Simvastatin should be administered not less than 2 hours before or not less than 4 hours after administration of bile acid sequestrants. When co-administered with gemfibrozil, ciclosporin, danazol, other fibrates (except fenofibrate) or niacin at lipid-lowering doses (≥ 1 g / day), the simvastatin dose should not exceed 10 mg / day; in patients taking Amiodarone or Verapamil, the dose of simvastatin should not exceed 20 mg daily. Do not exceed the 40 mg dose per day in patients taking concomitant diltiazem.
The maximum daily dose of the drug is 80 mg; this dose is recommended only for patients with severe hypercholesterolemia and a high risk of cardiovascular complications. Doses should be adjusted at intervals of at least 4 weeks.Patients with mild or moderate renal insufficiency and elderly patients do not need to change their dosage. In patients with severe renal impairment (creatinine clearance <30 ml / min), a daily dose of more than 10 mg should be carefully considered and, if necessary, very cautiously start treatment. Children and adolescents (10-17 years): the recommended dose is 10-40 mg per day; the maximum recommended dose is 40 mg daily. The dose should be adjusted individually for the recommended purpose, as recommended by pediatric treatment; the dose should be adjusted at intervals of 4 weeks or longer. In children and adolescents aged 10-17 years (boys on the Tanner scale, phase II and above and girls at least 1 year after the onset of the first menstruation) with familial hypercholesterolemia: the recommended dose is 10 mg once a day, in the evening; children and adolescents should use a standard low-cholesterol diet, which should be continued during therapy.