Index of drugs

Hypercholesterolemia. Treatment of primary hypercholesterolemia or mixed dyslipidemia, as a diet supplement, if 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 methods of reducing lipids (eg LDL apheresis) or if the use of these methods is not appropriate.Prevention of heart and vessel diseases. Reduction of morbidity and mortality from cardiovascular disease in patients with overt cardiovascular disease or diabetes mellitus, with normal or elevated cholesterol, as adjunctive therapy to correct other risk factors, and to supplement other treatments to prevent cardiovascular disease.

1 tabl powl. contains 40 mg of 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. 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 ingredients of the preparation. Active liver disease or persistent unexplained increase in serum transaminases. Pregnancy and breastfeeding. Concomitant administration of potent CYP3A4 inhibitors (eg Itraconazole, ketoconazole, posaconazole, HIV protease inhibitors, Erythromycin, Clarithromycin, telithromycin and nefazodone). Co-administration of gemfibrozil, cyclosporin or danazol.

Simvastatin may occasionally induce myopathy, sometimes leading to rhabdomyolysis (very rare cases of deaths have been reported). The risk of myopathy and / or rhabdomyolysis depends on the dose of the drug - the risk is higher in patients taking simvastatin 80 mg compared with other methods of reducing LDL cholesterol with statins of similar efficacy. The 80 mg dose of simvastatin is only recommended for patients with severe hypercholesterolaemia and high risk of cardiovascular complications who have not achieved treatment goals at lower doses and when the benefits are expected to outweigh the potential risk. Caution should be exercised in patients with the following predisposing factors for rhabdomyolysis: in elderly patients (≥ 65 years), women, patients with impaired renal function, and uncontrolled hypothyroidism, with hereditary disorders of the muscular system (including family history) , in patients with a history of toxic effects of statins or muscle fibrates and patients with alcohol dependence. In these groups, creatine kinase (CK) should be measured before 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. In patients requiring CK determination, it should not be measured after exhausting physical exertion or if there are any other alternative causes that increase CK activity (risk of false adulteration). If the CK activity is significantly greater than the ULN, the test should be repeated after 5 and, after 7 days at the latest, to confirm the result. 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. 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. Treatment should be discontinued a few days before the planned major surgery or in case of a severe disease or urgent surgery. The drug should be used with caution in people who consume significant amounts of alcohol. In patients suspected of having interstitial lung disease, treatment with statins should be discontinued. Some evidence suggests that statins increase blood Glucose levels and may cause hyperglycaemia - patients at risk (fasting blood glucose 5.6-6.9 mmol / l, BMI> 30 kg / m², increased triglycerides, hypertension) should be monitored both clinically and biochemically. The safety and efficacy of simvastatin in patients aged 10-17 years with familial heterozygous hypercholesterolemia has 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 measurable effect on sexual growth or puberty in adolescent 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, nor in sexually immature patients and girls prior to 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 drug should not be used in pregnant women and women planning pregnancy or those who are suspected of being pregnant. Women taking the drug should not breastfeed because of the possibility of serious side effects in the child.

Rare: anemia, headache, dizziness, paresthesia, peripheral neuropathy, constipation, abdominal pain, bloating, indigestion, diarrhea, nausea, vomiting, pancreatitis, hepatitis / jaundice, rash, pruritus, alopecia, myopathy, rhabdomyolysis with or without acute renal failure, muscle pain, muscle spasms, asthenia, elevation of aminotransferases, alkaline phosphatase, serum creatine kinase. Very rare: insomnia, memory problems, liver failure.Rare cases of hypersensitivity symptoms have been observed, such as: angioneurotic edema, lupus-like syndrome, rheumatoid type muscle pain, myositis and inflammation of the blood vessels, thrombocytopenia, eosinophilia, elevated OB, joint pain, arthritis, urticaria, photosensitivity, fever, redness, difficulty in breathing, feeling unwell. Frequency unknown: depression, interstitial lung disease, tendinopathy (sometimes complicated by tendon rupture), erectile dysfunction. In addition, some of the statins reported: sleep disorders, including nightmares, memory loss, sexual dysfunction, and diabetes.

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; 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 fibrates other than gemfibrozil or fenofibrates, the dose of coadministered simvastatin should not exceed 10 mg daily; in patients taking Amiodarone, Amlodipine, Verapamil or diltiazem, the dose of simvastatin should not exceed 20 mg daily. The maximum daily dose of the drug is 80 mg. Dose changes should be made at intervals of not less than 4 weeks. In patients with severe renal insufficiency (creatinine clearance <30 ml / min), simvastatin 10 mg should be considered, should such doses prove necessary, they should be used in particular carefully. No dosage adjustment is necessary for patients with moderate renal insufficiency or elderly patients.
Children and adolescents (10-17 years)the recommended dose is 10-40 mg / day; the maximum recommended dose is 40 mg daily. The dose should be adjusted individually to the expected result, according to the recommendations of pediatric treatment; increasing or decreasing doses should be done at intervals of 4 weeks or more. 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 per day, once in the evening; children and adolescents should use a standard low-cholesterol diet, which should be continued during therapy.