Index of drugs

Treatment of primary or mixed dyslipidemia with primary or secondary hypercholesterolaemia as a supplement to the diet when the response to diet or other nonpharmacological treatments (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 20 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. 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, HIV protease inhibitors, Erythromycin, Clarithromycin, telithromycin and nefazodone.

Use with caution in patients with predisposing factors for rhabdomyolysis: in elderly patients (over 70 years of age), with renal dysfunction, refractory or untreated hypothyroidism, with hereditary disorders of the muscular system (including family history), patients who have had muscle or alcohol-induced toxicity in the past with statins or fibrates. 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 severe and cause daily discomfort even when the CK activity is lower than 5 times the upper limit of normal. If myopathy is suspected for any reason, the medicine should be discontinued. If the muscle symptoms resolve 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 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: myopathy, rhabdomyolysis, muscle pain, muscle cramps, constipation, abdominal pain, flatulence, indigestion, diarrhea, nausea, vomiting, pancreatitis, hepatitis, jaundice, headache and dizziness, paresthesia, peripheral neuropathy, anemia, rash, pruritus , alopecia, asthenia, elevation of transaminases, GGTP, alkaline phosphatase, serum creatine kinase. Very rare: liver failure. Rare cases of hypersensitivity syndrome with symptoms such as: angioneurotic edema, lupus-like syndrome, rheumatoid-type muscle pain, myositis and skin inflammation, thrombocytopenia, eosinophilia, elevated OB, arthritis, arthralgia, urticaria, hypersensitivity to light, fever have been reported. hot flashes, shortness of breath, feeling unwell. Some statins showed: sleep disturbances, insomnia, nightmares, memory loss, sexual dysfunction, symptoms of depression, individual cases of interstitial lung disease (especially during long-term treatment).

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.
Dosage range is 5 mg - 80 mg administered once a day, orally, in the evening. 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. There is no need to change the dosage in patients with mild or moderate renal impairment or in elderly patients. In patients with acute renal failure (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 starting 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.