Rosuvastatin-LF tablets p / o in a box. box. 20 mg No. 10×3

Name:
Rosuvastatin-LF tabl.p/o 20mg per cont. cell pack. No. 10×3
Description:
Round tablets, biconvex, film-coated light pink. The main active ingredient Rosuvastatin Form of release Coated tablets Dosage 20 mg Pharmacological action Mechanism of action Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, an enzyme that catalyzes the conversion of 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a cholesterol precursor. The main organ that rosuvastatin acts on is the liver, the target organ for lowering cholesterol levels. Rosuvastatin increases the number of hepatic low density lipoprotein (LDL) receptors on the cell surface, increasing the uptake and catabolism of LDL, which leads to inhibition of the synthesis of very low density lipoprotein (VLDL), thereby reducing the total amount of LDL and VLDL. Pharmacodynamics Rosuvastatin reduces elevated levels of LDL-cholesterol (LDL-C), total cholesterol, triglycerides (TG), increases high-density lipoprotein cholesterol (HDL-C), and also reduces the content of apolipoprotein B (ApoB), cholesterol-non-HDL, cholesterol- VLDL, TG-VLDL and increases the level of apolipoprotein A-I (ApoA-I), reduces the ratio of LDL-C/HDL-C, total C/HDL-C and non-HDL-C/HDL-C and the ApoB/ApoA-I ratio. Table 1. Dose-dependent effect in patients with primary hypercholesterolemia (Fredrickson type IIa and IIb) (mean adjusted percentage change from baseline) – see instructions. The therapeutic effect is achieved 1 week after the start of treatment, 90% of the maximum effect is obtained after 2 weeks. The maximum effect is usually observed after 4 weeks and remains unchanged after this period. Clinical efficacy and safety Rosuvastatin is effective in adult patients with hypercholesterolemia, with or without hypertriglyceridemia, regardless of race, sex or age, as well as in patients with diabetes or a hereditary form of hypercholesterolemia. Pooled data from phase III clinical trials show that rosuvastatin has a clinical effect in the treatment of most patients with hypercholesterolemia types IIa and IIb (mean baseline LDL level is 4.8 mmol / l), which is recognized in the standards of the European Society for Atherosclerosis (EOA, 1998); the level of LDL-C met the norms of EOA (<3 mmol / l) in approximately 80% of patients who received a dose of 10 mg. In a large study, 435 patients with a heterozygous form of hereditary hypercholesterolemia received rosuvastatin at a dose of 20 mg to 80 mg. All doses showed a positive effect on lipid parameters. After titration to a daily dose of 40 mg (12 weeks of treatment), LDL-C was reduced by 53%. 33% of patients reached the EOA norm in terms of LDL-C level (<3 mmol/l). In an open titer study in 42 patients with a homozygous form of hereditary hypercholesterolemia, the clinical effect was evaluated when taking 20-40 mg of rosuvastatin. The average level of decrease in LDL-C among all patients was 22%. In clinical studies with a limited number of patients, data have been obtained that rosuvastatin has an additive effect on lowering triglyceride levels when used together with niacin. The JUPITER study (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) marked an important milestone in the primary prevention of cardiovascular disease with statins. The effect of rosuvastatin on the occurrence of major atherosclerotic cardiovascular diseases was evaluated in 17,802 men over 50 years of age and women over 60 years of age. Study participants were randomized to either placebo (n=8901) or rosuvastatin 20 mg once daily (n=8901) and were followed up for 2 years. LDL cholesterol decreased by 45% (p<0.001) in the rosuvastatin group compared to the placebo group. In a retrospective analysis of high-risk patients with a baseline Framingham risk score of >20% (1558 patients), rosuvastatin-treated patients had a significant reduction in the combined endpoint of cardiovascular death, stroke, and myocardial infarction (p = 0.028 ) compared with the placebo group. The absolute reduction in the incidence of such outcomes per 1000 patient-years was 8.8. Overall mortality remained unchanged in the high-risk group (p=0.193). In a retrospective analysis of high-risk patients (9302 patients) with a baseline risk of ?5% (extrapolated to include patients over 65 years of age), patients treated with rosuvastatin showed a significant reduction in the combined endpoint of mortality from cardiovascular causes, stroke and myocardial infarction (p=0.0003) compared with the placebo group. The absolute reduction in the incidence of these outcomes was 5.1 per 1000 patient-years. Overall mortality remained unchanged in the high-risk group (p=0.076). In the JUPITER study, 6.6% of patients in the rosuvastatin group and 6.2% of patients in the placebo group discontinued study medication due to adverse reactions. The most common adverse reactions leading to discontinuation of the drug were: myalgia (0.3% in the rosuvastatin group, 0.2% in the placebo group), abdominal pain (0.03% in the rosuvastatin group, 0.02% in the placebo group). placebo group) and rash (0.02% in the rosuvastatin group, 0.03% in the placebo group). The most common adverse reactions with a frequency greater than or equal to the placebo group were: urinary tract infections (8.7% in the rosuvastatin group, 8.6% in the placebo group), nasopharyngitis (7.6% in the rosuvastatin group, 7.2% in the placebo group). placebo), back pain (7.6% in the rosuvastatin group, 6.9% in the placebo group) and myalgia (7.6% in the rosuvastatin group, 6.6% in the placebo group). Children In a double-blind, randomized, multicenter, placebo-controlled, 12-week study (n=176, 97 men and 79 women), followed by a 40-week (n=173, 96 men and 77 women), open-label dose titration study of rosuvastatin, patients at the age of 10-17 years (II-V on the Tanner scale) with heterozygous hereditary hypercholesterolemia took 5, 10 or 20 mg of rosuvastatin or placebo daily for 12 weeks, and then all patients switched to rosuvastatin therapy for the next 40 weeks. The study included approximately 30% of patients aged 10-13 years and approximately 17%, 18%, 40% and 25% at Tanner stages II, III, IV and V, respectively. LDL cholesterol levels were reduced by 38.3%, 44.6% and 50.0% with 5, 10 and 20 mg of rosuvastatin, respectively, compared with 0.7% in the placebo group. At the end of week 40, 70 of 173 patients (40.5%) taking rosuvastatin at doses up to 20 mg once daily achieved an LDL cholesterol level of less than 2.8 mmol/l. After 52 weeks of the study, no effect of rosuvastatin treatment on height, weight, body mass index or puberty was found. Rosuvastatin was also studied in a 2-year, open-label, dose-titrated to target study in 198 children aged 6 to 17 years with heterozygous familial hypercholesterolemia (88 males and 110 females). IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as an adjunct to diet when diet and other non-drug treatments (eg, exercise, weight loss) are inadequate in adults, adolescents, and children over 6 years of age. Familial homozygous hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (eg, LDL apheresis), or in cases where such therapy is not effective enough. Prevention of cardiovascular disease: To reduce the risk of severe cardiovascular complications in adult patients without clinical signs coronary artery disease, but with an increased risk of its development (age over 50 years for men and over 60 years for women, increased concentration of C-reactive protein (? 2 mg / l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low concentration of HDL-C, smoking, family history of early onset of coronary artery disease). drinking water. The drug can be taken at any time of the day, regardless of food intake. Prior to initiation of therapy with Rosuvastatin-LF, the patient should begin to follow a standard hypocholesterolemic diet and continue to follow it during treatment. The dose of the drug should be individualized depending on the goals of therapy and therapeutic response to treatment, taking into account current recommendations for target lipid concentrations. Treatment of hypercholesterolemia The recommended initial dose for patients starting the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, should be 5 ml of 10 mg Rosuvastatin-LF once a day. When choosing an initial dose, one should be guided by the individual cholesterol level and take into account the possible risk of cardiovascular complications, and it is also necessary to evaluate the potential risk of side effects. If necessary, the dose may be increased to a higher dose after 4 weeks. Due to the possible development of side effects when taking a dose of 40 mg, compared with lower doses of drugs, an increase in dose to 40 mg, after an additional dose above the recommended initial dose for 4 weeks of therapy, can be carried out only in patients with severe hypercholesterolemia and with a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia), who have not achieved the desired result of therapy when taking a dose of 20 mg, and who will be under the supervision of a specialist. Particularly careful monitoring of patients receiving the drug at a dose of 40 mg is recommended. Prevention of cardiovascular diseases The recommended dose of rosuvastatin is 20 mg per day. Use in children Use in children can only be carried out under the supervision of specialists. Children and adolescents aged 6 to 17 years (boys with a score of 2 or more on the Tanner scale) The initial dose of rosuvastatin for children and adolescents with heterozygous hereditary hypercholesterolemia is 5 mg once a day. For children aged 6-9 years with heterozygous hereditary hypercholesterolemia, the recommended dose is 5-10 mg orally once a day. The safety and efficacy of doses of rosuvastatin greater than 10 mg have not been studied in this group of patients. For children aged 10-17 years with heterozygous hereditary hypercholesterolemia is 5-20 mg once a day. The safety and efficacy of doses of rosuvastatin greater than 20 mg have not been studied in this group of patients. The dosage is selected individually for each patient, depending on the response of the child to the therapy. Before starting rosuvastatin therapy, children and adolescents should start a standard cholesterol-lowering diet and continue to follow it during treatment. Experience with rosuvastatin in children with homozygous hereditary hypercholesterolemia is limited to a small number of patients aged 8 to 17 years. The use of the drug at a dose of 40 mg is not recommended for this group of patients. Children under 6 years of age The safety and efficacy of rosuvastatin in children under 6 years of age has not been studied. Therefore, the use of Rosuvastatin-LF is not recommended for children under 6 years of age. Elderly patients For patients over 70 years of age, the recommended starting dose is 5 mg. Changes in the dosing regimen in this group of patients are not required. Patients with renal insufficiency In patients with mild or moderate renal insufficiency, dose adjustment is not required. The recommended starting dose is 5 mg for patients with moderate renal impairment (creatinine clearance <60 ml/min). The use of the drug at a dose of 40 mg in patients with moderate renal insufficiency is contraindicated. In patients with severe renal insufficiency (creatinine clearance <30 ml / min), the use of Rosuvastatin-LF is contraindicated. Patients with hepatic insufficiency No increase in systemic exposure to rosuvastatin was observed in patients with Child-Pugh values of 7 or below. However, increased systemic exposure to rosuvastatin has been observed in individuals with Child-Pugh values of 8 and 9. In these patients, renal function should be assessed. Data on individuals with Child-Pugh values above 9 are not available. Rosuvastatin-LF is contraindicated in patients with active liver disease. special populations. Race There has been an increase in the systemic concentration of rosuvastatin among Asian patients. The recommended starting dose for these patients is 5 mg. The dose of the drug 40 mg is contraindicated in this category of patients. Genetic polymorphism In carriers of the genotypes SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421 AA, an increase in exposure (AUC) to rosuvastatin was noted compared with carriers of the genotypes SLCO1B1 c.521TT and ABCG2 c.421CC. For patients carrying genotypes c.521 CC or c.421AA, the recommended maximum dose of Rosuvastatin-LF is 20 mg once a day. Patients predisposed to myopathy Prescribing the drug at a dose of 40 mg is contraindicated in patients with factors that may indicate a predisposition to the development of myopathy. The recommended starting dose for this group of patients is 5 mg. Concomitant Therapy Rosuvastatin binds to various transport proteins (particularly OATP1B1 and BCRP). When Rosuvastatin-LF is co-administered with medicinal products (such as cyclosporine, certain HIV protease inhibitors, including the combination of ritonavir with atazanavir, lopinavir and/or tipranavir) that increase plasma concentrations of rosuvastatin by interacting with transport proteins, the risk of myopathy may be increased (including rhabdomyolysis). In such cases, the possibility of prescribing alternative therapy or temporarily stopping rosuvastatin should be evaluated. If the use of the above drugs is necessary, the benefit-risk ratio of concomitant therapy with rosuvastatin should be assessed and the possibility of reducing its dose should be considered. Use during pregnancy and lactation Pregnancy The use of rosuvastatin during pregnancy can lead to the formation of serious birth defects in infants. The use of Rosuvastatin-LF is contraindicated during pregnancy. Women of childbearing age should use adequate contraceptive methods while taking the drug. Since cholesterol and other products of cholesterol biosynthesis are important for fetal development, the potential risk of HMG-CoA reductase inhibition outweighs the benefit of the drug in pregnant women. Animal studies provide only limited data on reproductive toxicity. In the event of pregnancy during therapy, the drug should be discontinued immediately. Lactation period Rosuvastatin is found in the breast milk of rats. There are no data on the excretion of rosuvastatin in human breast milk, so the drug should be discontinued during breastfeeding. Influence on the ability to drive vehicles and work with mechanisms No studies have been conducted to study the effect of rosuvastatin on the ability to drive a vehicle and use mechanisms. Care should be taken when driving vehicles or work that requires increased concentration and speed of psychomotor reactions (during therapy, dizziness may occur). PrecautionsImpaired kidney function In patients receiving high doses of rosuvastatin (mainly 40 mg), proteinuria (mainly tubular) was observed, which in most cases was transient. Such proteinuria was not indicative of acute kidney disease or progressive renal failure. The frequency of serious impairment of renal function identified in post-marketing studies was higher at a dose of 40 mg. In patients taking the drug at a dose of 40 mg, it is recommended to monitor indicators of kidney function during treatment. Musculoskeletal disorders When using rosuvastatin at all doses, and especially when taking doses of rosuvastatin in excess of 20 mg, the following side effects from the musculoskeletal system were observed: myalgia, myopathy, in rare cases, rhabdomyolysis. Rare cases of rhabdomyolysis have been observed in patients receiving ezetimibe in combination with HMG-CoA reductase inhibitors. A pharmacodynamic interaction of these medicinal products cannot be ruled out and caution should be exercised when co-administering them. As with other HMG-CoA reductase inhibitors, reports of rhabdomyolysis with rosuvastatin in the post-marketing period were mainly associated with rosuvastatin 40 mg. Determination of creatine phosphokinase activity Determination of CPK activity should not be carried out after intense physical exertion or in the presence of other possible reasons for an increase in CPK activity, which may lead to incorrect interpretation of the results. If the initial activity of CPK is significantly increased (5 times higher than the upper limit of the norm), after 5-7 days a second measurement should be taken. You should not start therapy if a repeat test confirms the initial activity of CPK (more than 5 times higher than the upper limit of normal). Prior to therapy When prescribing rosuvastatin, as well as when prescribing other inhibitors of HMG-CoA reductase, caution should be exercised in patients with existing risk factors for myopathy / rhabdomyolysis. These factors are: Renal failure; Hypothyroidism; Muscular disorders in the patient's history or family history; Previous exposure to muscle toxicity when taking another HMG-CoA reductase inhibitor or fibrate; Alcohol dependence; Age over 70 years; Situations in which an increase is possible plasma concentrations; Combined use with fibrates. In such patients, it is necessary to consider the ratio of risk and possible benefit of therapy and conduct clinical observation. If the initial level of CPK exceeds 5 times the normal level of CPK, treatment cannot be started. During therapy The patient should be informed about the need to immediately inform the doctor about cases of sudden onset of muscle pain, muscle weakness or spasms, especially in combination with malaise and fever. In such patients, CPK activity should be determined. Therapy should be discontinued if CPK activity is significantly increased (more than 5 times the upper limit of normal) or if muscle symptoms are pronounced and cause daily discomfort (even if CPK activity is increased no more than 5 times compared to upper limit of normal). If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing Rosuvastatin-LF or other HMG-CoA reductase inhibitors at lower doses with careful monitoring of the patient. Routine monitoring of CPK activity in the absence of symptoms is impractical. There have been very rare cases of immune-mediated necrotizing myopathy with clinical manifestations in the form of persistent weakness of the proximal muscles and an increase in serum CK activity during treatment or upon discontinuation of statins, including rosuvastatin. Additional studies of the muscular and nervous system, serological studies, as well as immunosuppressive therapy may be required. There were no signs of increased exposure to skeletal muscle when taking rosuvastatin and concomitant therapy. However, an increase in the incidence of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibric acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid in lipid-lowering doses (more than 1 g / day), azole antifungals, HIV protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when co-administered with certain HMG-CoA reductase inhibitors. Thus, the simultaneous use of Rosuvastatin-LF and gemfibrozil is not recommended. The ratio of risk and possible benefit should be carefully weighed when using the drug Rosuvastatin-LF and fibrates or lipid-lowering doses of nicotinic acid together. It is contraindicated to take the drug Rosuvastatin-LF at a dose of 40 mg together with fibrates. Liver As with other HMG-CoA reductase inhibitors, rosuvastatin should be used with caution in patients who consume excessive amounts of alcohol or have a history of liver disease. It is recommended to carry out the determination of indicators of liver function before the start of therapy and 3 months after the start of therapy. Taking the drug Rosuvastatin-LF should be discontinued or its dose reduced if the activity of "liver" transaminases in the blood serum is 3 times the upper limit of normal. In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of underlying diseases should be carried out before starting treatment with Rosuvastatin-LF. special populations. Ethnic groups In the course of pharmacokinetic studies among patients of Asian origin, an increase in the systemic concentration of rosuvastatin was noted in comparison with the values obtained among Caucasian patients. HIV protease inhibitors The concomitant use of the drug with protease inhibitors is not recommended. Lactose The drug should not be used in patients with lactase deficiency, galactose intolerance and glucose-galactose malabsorption. Interstitial lung disease With the use of some statins, especially for a long time, isolated cases of interstitial lung disease have been reported. Symptoms of the disease may include shortness of breath, dry cough and deterioration in general well-being (weakness, weight loss and fever). If interstitial lung disease is suspected, statin therapy should be discontinued. Type 2 diabetes Some evidence suggests that statins can increase blood glucose levels and, in patients with a predisposition to diabetes, can lead to a level of hyperglycemia at which it is reasonable to prescribe diabetes mellitus treatment. However, the benefit of statin treatment outweighs this risk, and therefore discontinuation of statin therapy is not required. Patients with a glucose concentration of 5.6 to 6.9 mmol/l, BMI>30 kg/m2, elevated triglycerides, hypertension should be under careful clinical and biochemical monitoring in accordance with national requirements. In a clinical study conducted, the overall incidence of diabetes mellitus was 2.8% in the rosuvastatin group and 2.3% in the placebo group, mainly in patients with fasting glucose levels of 5.6 to 6.9 mmol / l. Children Assessment of linear height (height), weight, BMI (body mass index), and secondary characteristics of puberty according to the Tanner scale in children aged 10 to 17 years taking rosuvastatin is limited to a period of 1 year. After 52 weeks of the study, no effect of rosuvastatin treatment on height, weight, body mass index or puberty was found. Clinical experience with the drug in children and adolescents is limited, and the long-term effect of rosuvastatin (>1 year) on puberty is unknown. In clinical studies in children and adolescents taking rosuvastatin for 52 weeks, CPK levels were increased (> 10 times the upper limit of normal), muscle symptoms after exercise or after increased physical activity are observed more often compared with observations during clinical trials. tests in adults. Interactions with other drugs The effect of the use of other drugs on rosuvastatin Inhibitors of transport proteins: rosuvastatin binds to some transport proteins, in particular, OATP1B1 and BCRP. The concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the plasma concentration of rosuvastatin and an increased risk of myopathy (see table 2). Cyclosporine: With the simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was on average 7 times higher than the value observed in healthy volunteers (see table 2). Does not affect the plasma concentration of cyclosporine. Rosuvastatin-LF is contraindicated in patients taking cyclosporine. Human Immunodeficiency Virus (HIV) Protease Inhibitors: Although the exact mechanism of interaction is unknown, co-administration of HIV protease inhibitors can lead to a significant increase in exposure to rosuvastatin (see Table 2). A pharmacokinetic study on the simultaneous use of 20 mg rosuvastatin with a combination drug containing two HIV protease inhibitors (400 mg lopinavir/100 mg ritonavir) in healthy volunteers resulted in an approximately two-fold and five-fold increase in AUC (0-24) and Cmax of rosuvastatin, respectively. Therefore, the simultaneous use of rosuvastatin and HIV protease inhibitors is not recommended (see table 2). Gemfibrozil and other lipid-lowering agents: The combined use of rosuvastatin and gemfibrozil leads to a 2-fold increase in the maximum plasma concentration of rosuvastatin and the AUC of rosuvastatin. Based on specific interaction data, a pharmacokinetically significant interaction with fenofibrate is not expected, a pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates, and lipid-lowering doses of nicotinic acid increased the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy when used alone. While taking rosuvastatin with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day), patients are recommended an initial dose of the drug 5 mg, taking a dose of 40 mg is contraindicated when administered together with fibrates. Ezetimibe: The simultaneous use of rosuvastatin at a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase in the AUC of rosuvastatin in patients with hypercholesterolemia (see table 2). An increased risk of side effects due to a pharmacodynamic interaction between rosuvastatin and ezetimibe cannot be ruled out. Antacids: The simultaneous use of rosuvastatin and suspensions of antacids containing magnesium and aluminum hydroxide leads to a decrease in the plasma concentration of rosuvastatin by approximately 50%. This effect is less pronounced if antacids are applied 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied. Erythromycin: the simultaneous use of rosuvastatin and erythromycin leads to a decrease in the AUC of rosuvastatin by 20% and the Cmax of rosuvastatin by 30%. This interaction may occur as a result of increased intestinal motility caused by erythromycin. Cytochrome P450 isoenzymes: In vivo and in vitro studies have shown that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, the interaction of rosuvastatin with other drugs at the level of metabolism with the participation of cytochrome P450 isoenzymes is not expected. There was no clinically significant interaction of rosuvastatin with fluconazole (an inhibitor of CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of CYP2A6 and CYP3A4 isoenzymes). Drug interactions that require dose adjustment of rosuvastatin (see Table 2) The dose of rosuvastatin should be adjusted if it is necessary to co-administer it with drugs that increase exposure to rosuvastatin. You should also read the instructions for the medical use of these drugs before prescribing them together with rosuvastatin. If an increase in exposure of 2 times or more is expected, the initial dose of rosuvastatin should be 5 mg once a day. The maximum daily dose of the drug Rosuvastatin-LF should also be adjusted so that the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg taken without the simultaneous administration of drugs that interact with rosuvastatin. For example, the maximum daily dose of the drug Rozuv