Index of drugs

Treatment of primary hypercholesterolaemia or mixed dyslipidemia, as a diet supplement, when the response to diet or other nonpharmacologic 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. 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 10 mg, 20 mg, 40 mg or 80 mg of simvastatin. The preparation contains lactose.

The active metabolite of Simvastatin (beta-hydroxy acid) is a potent inhibitor of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMG-CoA). This enzyme catalyzes the conversion of HMG-CoA to mevalonate, i.e. an early, limiting reaction of the cholesterol biosynthesis step. 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 plasma triglyceride levels. After oral administration of Simvastatin, less than 5% of the β-hydroxy acid from the administered dose gets into the systemic circulation. 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: β-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 unexplained, persistent increase in serum transaminases. Pregnancy and breastfeeding. Concomitant use of strong CYP3A4 inhibitors (eg Itraconazole, ketoconazole, Fluconazole, posaconazole, HIV protease inhibitors, Erythromycin, Clarithromycin, telithromycin and nefazodone). Concomitant use of gemfibrozil, cyclosporine or danazol.

Carefully use in patients with predisposing factors for rhabdomyolysis: in elderly patients (> 65 years), with impaired renal function, with uncontrolled hypothyroidism, with hereditary disorders of the muscular system (including family history), in patients which have previously had toxic effects of statins or muscle fibrates, in patients with alcohol dependence and in female 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 symptoms are significantly increased even when the CK activity is less than 5 times the upper limit of normal. 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. The risk of myopathy is higher in patients taking the 80 mg dose of simvastatin. Therefore, this dose should only be recommended to patients with severe hypercholesterolaemia and high risk of cardiovascular complications who have not achieved therapeutic goals using lower doses and when the expected benefits outweigh the potential risks. 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 aminotransferases persists, especially if it reaches 3 times the upper limit of normal and will persist. The drug should be used with caution in people who consume significant amounts of alcohol. Some data suggest that all statin drugs increase blood Glucose levels and in some patients at high risk of developing diabetes in the future, they may cause hyperglycaemia with severity requiring appropriate diabetes care. This risk is however outweighed by the benefit of reducing the risk of developing vascular disease, so statin therapy should not be discontinued. Patients at risk (patients with fasting glucose from 5.6 to 6.9 mmol / l, BMI> 30kg / m², with elevated triglycerides, hypertension) should be subjected to clinical and biochemical monitoring according to local guidelines. 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 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 is contraindicated during pregnancy and while breastfeeding. Treatment with simvastatin should be discontinued for the duration of pregnancy or until its exclusion.

Rare: anemia; headache, dizziness, paresthesia, peripheral neuropathy; constipation, abdominal pain, flatulence, indigestion, diarrhea, nausea, vomiting, pancreatitis; hepatitis / jaundice; rash, pruritus, baldness; myopathy (including myositis), rhabdomyolysis with or without acute renal failure, myalgia, muscle cramps; asthenia, hypersensitivity syndrome (angioneurotic edema, lupus-like syndrome, rheumatic polymyalgia, dermatomyositis, vasculitis, thrombocytopenia, eosinophilia, accelerated ESR, inflammation and pain in the joints, urticaria, hypersensitivity to light, fever with redness of the skin, shortness of breath and feeling unwell ); increase in transaminases (ALT, AST, GGT), increase in alkaline phosphatase and increase in serum CK. Very rare: insomnia; memory disorders; hepatic failure (also leading to death). Frequency unknown: depression; interstitial lung disease; tendinitis (sometimes with a complication of a hernia); erectile dysfunction. During therapy with statins, including simvastatin, increases in HbA1c and fasting plasma glucose have been reported. Side effects characteristic of drugs in this group: sleep disorders, including nightmares; loss of memory, sexual dysfunction, diabetes (frequency depends on the presence or absence of risk factors).

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; 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 other fibrates (except fenofibrate and gemfibrozil), the dose of coadministered simvastatin should not exceed 10 mg daily; in patients taking Amiodarone, Amlodipine, dilitiazem 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 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 youth (boys in the second stage of development according to Tanner's scale or above and girls at least one year from the onset of menarche, aged 10-17 years) with heterozygous familial hypercholesterolaemia: the recommended starting dose is 10 mg per day, in the evening. Before starting treatment, children and adolescents should use a standard cholesterol-lowering diet and continue this diet during treatment with simvastatin. Dosage range is from 10 mg to 40 mg simvastatin daily, the maximum recommended dose is 40 mg daily. Doses should be adjusted individually at intervals of 4 weeks or longer.