Index of drugs

Hypercholesterolemia. Treatment of primary hypercholesterolaemia or mixed dyslipidemia, as a supplement to the diet, when the response to diet and other non-pharmacological treatments (eg physical exercise, weight loss) is insufficient. Treatment of familial homozygous hypercholesterolemia, as a supplement to diet and other methods leading to a reduction in lipids (eg LDL apheresis) or when these methods prove to be inappropriate.Prevention of events from the cardiovascular system. Decrease of mortality and morbidity of cardiovascular disease in patients with symptomatic atherosclerosis or diabetes mellitus, with normal or elevated cholesterol, as adjunctive therapy to correct other risk factors and supplement other therapy to prevent heart disease.

1 tabl powl. contains 10 mg, 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 catalyses the conversion of HMG-CoA to mevalonate, an early and also the control stage of cholesterol biosynthesis. Simvastatin reduces both normal and elevated LDL cholesterol. The mechanism of LDL cholesterol lowering by simvastatin may be the result of both lowering VLDL cholesterol and stimulating the LDL receptor, 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 about 1-2 hours after administration. Simvastatin and the active metabolite bind to plasma proteins 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 any of the excipients. Active liver disease or unexplained, persistent increase in serum transaminases. Pregnancy and breastfeeding. Concomitant use of strong CYP3A4 inhibitors (eg Itraconazole, ketoconazole, Fluconazole, posaconazole, HIV protease inhibitors (eg nelfinavir), Erythromycin, Clarithromycin, telithromycin and nefazodone.

Use with caution in patients with predisposing factors for rhabdomyolysis: elderly patients (over 70 years of age), renal dysfunction, decompensated hypothyroidism with pre-existing history of muscle disease, in patients who have previously received statins or fibrates caused muscle side effects and alcohol abusing patients. 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 side effects are severe and cause daily discomfort even when 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 disorder resolves and CK activity returns to normal, re-initiation of simvastatin or other statin therapy at the lowest effective dose may be considered and the patient's health status carefully monitored. Treatment should be temporarily interrupted for a few days before the planned major surgery or in case of serious diseases requiring medical or surgical treatment.Special care should be taken in patients who have elevated serum transaminases. The drug should be discontinued if there is a tendency to increase transaminase levels, especially when 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 has been evaluated in controlled clinical trials: in boys in the second stage of development and above the Tanner scale and girls at least 1 year after the onset of menstruation. Doses greater than 40 mg were not tested in this population. In this limited controlled study, there was no apparent effect on the development or sexual maturation of adolescent boys and girls or any effect on the length of the menstrual cycle in girls. In patients under 18 years, efficacy and safety have not been studied in periods of use longer than 48 weeks and the effect of long-term simvastatin on physical, intellectual and sexual maturation is not known. Simvastatin has not been studied in patients less than 10 years of age, nor in pre-pubertal children nor in girls before the onset of menstruation. The drug contains lactose - should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.

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

Rare: increased transaminases (ALT, AST, γ-GT), increased alkaline phosphatase, increased CK creatine kinase activity, anemia, headache and dizziness, paresthesia, peripheral neuropathy, constipation, abdominal pain, flatulence, indigestion, diarrhea, nausea, vomiting, pancreatitis, rash, pruritus, alopecia, myopathy, rhabdomyolysis, muscle pain, muscle cramps, asthenia, hepatitis / jaundice, cases of alleged hypersensitivity syndrome (with symptoms: angioneurotic edema, lupus-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, thrombocytopenia, eosinophilia, increased ESR, arthritis and joint pain, urticaria, hypersensitivity to light, fever, redness of the skin, shortness of breath and malaise). Very rare: memory loss, liver failure. In addition, the following side effects have been reported with statins: sleep disorders (including insomnia and nightmares), memory loss, sexual dysfunction, depression, isolated cases of interstitial lung disease, especially during long-term therapy.

Orally. Adults. The dosage range is 5-80 mg per day in a single dose taken orally in the evening. If necessary, the dose should be adjusted at intervals of at least 4 weeks up to a maximum single dose of 80 mg per day taken in the evening. The 80 mg dose is only recommended for patients with severe hypercholesterolemia and high risk of cardiovascular complications who have not responded to treatment at lower doses and when the expected benefit outweighs the potential risk.hypercholesterolemia: the starting dose is usually 10-20 mg once a day, in the evening; if it is necessary to reduce the LDL cholesterol by more than 45%, the starting 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). Simvastatin should be used in these patients as adjunctive therapy to other lipid-lowering methods (eg LDL apheresis) or when these methods are not available.Prevention of heart and vessel diseasesthe recommended dose is 20-40 mg once a day in the evening; treatment should begin with the introduction of diet and exercise.Combination therapy: Simvastatin should be administered not less than 2 hours before or not less than 4 hours after administration of bile acid sequestrants.When used with gemfibrozil, ciclosporin, danazol, other fibrates (except fenofibrate) the dose of simvastatin should not exceed 10 mg daily; in patients taking Amiodarone or Verapamil, the dose of simvastatin should not exceed 20 mg daily. Do not exceed the 40 mg dose a day for patients using diltiazem concomitantly. There is no need to change the dosage in patients with moderate renal impairment or in elderly. 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, cautioned treatment should be initiated. Children and adolescents (10-17 years): the recommended dose is 10-40 mg per day; the maximum recommended dose is 40 mg daily. Doses should be varied depending on the method of treatment in accordance with the instructions for use in children and adolescents; 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 heterozygous hypercholesterolemia: the recommended dose is 10 mg once a day, in the evening; children and adolescents: a standard serum cholesterol-lowering diet is recommended, which should be continued during treatment.