Index of drugs

Treatment of primary hypercholesterolemia in combination with diet when the response to diet or other non-pharmacological treatments (eg physical exercise, weight loss) is insufficient. Prevention of events from the cardiovascular system. Decrease of morbidity and mortality due to 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 therapy to prevent heart disease. Treatment should be taken as accompanying diet and other non-pharmacological methods (eg physical exercise and weight reduction).

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 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, HIV protease inhibitors, Erythromycin, Clarithromycin, telithromycin and nefazodone). Myopathy.

Caution in patients with predisposing factors for rhabdomyolysis: in elderly patients (> 70 years), with renal dysfunction, with refractory or untreated 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 in patients with alcohol dependence. 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. 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 (fasting glucose level from 5.6 to 6.9 mmol / l, BMI> 30 kg / m², with elevated triglycerides, hypertension) should be subjected to clinical and biochemical monitoring according to local guidelines. The product contains lactose - should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose. Due to the content of butyl hydroxyanisole, hypersensitivity reactions may occur in the form of irritation of the skin, eyes and mucous membranes.

Do not use the drug in pregnant women, in 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, flatulence, indigestion, diarrhea, nausea, vomiting, pancreatitis, hepatitis, jaundice, rash, pruritus, alopecia, myopathy, rhabdomyolysis , muscle pain, muscle cramps, asthenia, elevation of aminotransferases, alkaline phosphatase, serum creatine kinase. Rare cases of hypersensitivity symptoms have been observed, such as: angioneurotic edema, lupus-like syndrome, rheumatoid type muscle pain, myositis and skin inflammation, vasculitis, thrombocytopenia, eosinophilia, elevated OB, joint pain, arthritis, urticaria, photosensitivity, fever, hot flashes, shortness of breath, feeling unwell. 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.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 ciclosporin, danazol, gemfibrozil, 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.
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.