Mertenil tablets p/o 20mg №10×3

Name:
Mertenil tabl, p / captivity. obol. 20mg in a blister in pack No. 10×3
Description:
Film-coated tablets, 5 mg: White or almost white, round biconvex film-coated tablets, approx. One side of the tablet is engraved with “C33”. Film-coated tablets, 10mg: White or almost white, round biconvex film-coated tablets, approx. On one side of the tablet there is an engraving “C34”. Film-coated tablets, 20 mg: White or almost white, round biconvex film-coated tablets, approx. On one side of the tablet there is an engraving “C35”. The main active ingredient Rosuvastatin Form of release Tablets Dosage 5 mg, 10 mg, 20 mg Pharmacological properties Pharmacodynamics Mechanism of action Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A into mevalonate, which is a cholesterol precursor. The main target of rosuvastatin is the liver, where cholesterol (Cholesterol) is synthesized and low-density lipoprotein (LDL) is catabolized. Rosuvastatin increases the number of “liver” LDL receptors on the cell surface, increasing the uptake and catabolism of LDL. It also inhibits the synthesis of very low density lipoprotein (VLDL) cholesterol in liver cells, thereby reducing total LDL and VLDL. Pharmacodynamic effects Rosuvastatin reduces elevated cholesterol – LDL (LDL-C), total cholesterol and triglycerides (TG), increases high-density lipoprotein cholesterol (HDL-C), and also reduces the content of apolipoprotein B (ApoB), cholesterol-non-HDL (content total cholesterol minus HDL cholesterol), VLDL-C, VLDL-TG and increases the level of apolipoprotein A-I (ApoA-I) (see table 1). Rosuvastatin reduces the ratio of LDL-C/HDL-C, total C/HDL-C, non-HDL-C/HDL-C and ApoB/ApoA-I. Table 1. Dose response in patients with primary hypercholesterolemia (type IIa and IIb) (mean adjusted percentage change from baseline). Dose Number of patients LDL-C Total HDL-HDL-C TG Non-HDL-C Apo B Apo A-I Placebo 13 -7 -5 3 -3 -7 -3 0 5 mg 17 -45 -33 13 -35 -44 -38 4 10 mg 17 -52 -36 14 -10 -48 -42 4 20 mg 17 -55 -40 8 -23 -51 -46 5 40 mg 18 -63 -46 10 -28 -60 -54 0 Therapeutic effect can be achieved within one week after the start of treatment, after 2 weeks 90% of the maximum possible effect is achieved. Usually, the maximum possible therapeutic effect is achieved after 4 weeks and is maintained with further use of the drug. Clinical efficacy Rosuvastatin is effective in the treatment of adult patients with hypercholesterolemia with or without symptoms of hypertriglyceridemia, regardless of their race, sex or age, as well as in the treatment of a special category of patients – patients with diabetes mellitus or a hereditary form of familial hypercholesterolemia. Rosuvastatin is effective for the treatment of patients with Frederickson type IIa and IIb hypercholesterolemia (mean initial LDL-C level of about 4.8 mmol / l). In 80% of patients treated with 10 mg of rosuvastatin, the target values of LDL-C levels set by the European Society for the Study of Atherosclerosis (less than 3 mmol / l) were achieved. In patients with heterozygous familial hypercholesterolemia who took rosuvastatin in doses of 20 to 80 mg according to the forced dose titration scheme, all doses taken had a significant effect on changing lipid parameters and on achieving the goal of therapy. As a result of titration of doses up to 40 mg per day (12 weeks of therapy), the content of LDL-C decreased by 53%. In 33% of patients, LDL-C values (below 3 mmol/l) were achieved, corresponding to the target standards of the guidelines of the European Society for the Study of Atherosclerosis. In patients with homozygous familial hypercholesterolemia who took rosuvastatin at doses of 20 and 40 mg, the average decrease in LDL-C was 22%. An additive effect is observed in combination with fenofibrate in relation to a decrease in the content of TG and with nicotinic acid (more than a day) in relation to an increase in the content of HDL-C. In patients at low risk for coronary artery disease (defined as a Framingham risk of less than 10% over 10 years), with a mean LDL-C of 4.0 mmol/L (154.5 mg/dL), rosuvastatin in at a dose of 40 mg/day significantly slowed the increase in the maximum value characterizing the thickening of the carotid wall in 12 segments, compared with placebo at a rate of -0.0145 mm/year (95% confidence interval (CI): from -0.0196 to -0.0093, at p<0.0001). The 40 mg dose should only be given to patients with severe hypercholesterolemia and a high risk of developing cardiovascular disease. In patients with a high risk of coronary heart disease (Framingham risk of more than 20%), treatment with rosuvastatin showed a significant reduction in mortality from cardiovascular diseases, stroke and myocardial infarction. The overall mortality rate did not change in this risk group. Children and adolescents In a double-blind, randomized, multicenter, placebo-controlled, 12-week study (N=176, 97 boys and 79 girls aged 10-17 years, Tanner scale, girls not earlier than one year after menarche), LDL-C decreased by 38.3%, 44.6% and 50.0% with once daily rosuvastatin 5, 10 or 20 mg, respectively, compared with 0.7% in the placebo group. At the end of week 40 of subsequent dose titration to a maximum dose of 20 mg once a day, 40.5% achieved LDL-C levels of less than 2.8 mmol / l. There was no effect of rosuvastatin on height, body weight, BMI (body mass index) or puberty after 52 weeks of treatment. Experience with rosuvastatin in children and adolescents is limited, and the long-term effects of rosuvastatin (>1 year) on puberty are unknown. PharmacokineticsAbsorption: the maximum concentration of rosuvastatin in plasma is reached 5 hours after ingestion of the appropriate dose. Absolute bioavailability is approximately 20%. Distribution: Rosuvastatin is absorbed primarily by the liver, which is the main site for cholesterol synthesis and clearance of LDL-C metabolism. The volume of distribution of rosuvastatin is approximately . 90% of rosuvastatin binds to plasma proteins, mainly albumin. Metabolism: undergoes limited metabolism (approximately 10%). Rosuvastatin is a rather non-core substrate for metabolism by enzymes of the cytochrome P450 system. CYP2C9 is the main isoenzyme involved in metabolism, while the isoenzymes CYP2C19, CYP3A4 and CYP2D6 are involved in metabolism to a lesser extent. The main metabolite is N-desmethyl, which is 50% less active than rosuvastatin. Lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity of inhibiting circulating HMG-CoA reductase is provided by rosuvastatin, the rest is its metabolites. Excretion: Approximately 90% of the administered dose of rosuvastatin is excreted unchanged from the body through the intestines (including absorbed and unabsorbed rosuvastatin), and the remainder is excreted unchanged by the kidneys. The half-life (T1 / 2) is 19 hours, does not change with increasing dose of the drug. The geometric mean plasma clearance is approximately 50 l/h (coefficient of variation 21.7%). As in the case of other inhibitors of HMG-CoA reductase, the membrane carrier of cholesterol through the membranes, the transport protein C of organic anions, is involved in the process of “hepatic” uptake of rosuvastatin. This carrier plays an important role in the elimination of rosuvastatin by the liver. Linearity: Systemic exposure to rosuvastatin increases in proportion to dose. Changes in pharmacokinetic parameters when taking the drug several times a day are not observed. Pharmacokinetics in selected groups of patients Age and gender: gender and age do not have a clinically significant effect on the pharmacokinetic parameters of rosuvastatin in adults. The pharmacokinetics of rosuvastatin in children and adolescents with familial hypercholesterolemia did not differ from that in healthy adult volunteers. Race: Comparative pharmacokinetic studies have shown a two-fold increase in the mean AUC (area under the concentration-time curve) and Cmax (maximum plasma concentration of rosuvastatin) in patients of Asian origin (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with indicators in representatives of the Caucasian race. In Indians, an excess of about 1.3 times the average value of AUC and Cmax was noted. At the same time, the analysis of pharmacokinetic indicators for the entire study population did not reveal clinically significant differences in the pharmacokinetics of the drug among representatives of Caucasian, Negroid races, Hispanics. Renal insufficiency: in patients with mild to moderate renal insufficiency, the plasma concentration of rosuvastatin or the N-desmethyl metabolite does not change significantly. In patients with severe renal insufficiency (creatinine clearance (CC) less than 30 ml / min), the concentration of rosuvastatin in plasma is 3 times higher, and the concentration of N-desmethyl metabolite is 9 times higher compared to healthy volunteers. The plasma concentration of rosuvastatin in patients on hemodialysis was approximately 50% higher than in healthy volunteers. Hepatic insufficiency: in patients with varying degrees of hepatic insufficiency with a score of 7 or below on the Child-Pugh scale, an increase in exposure to rosuvastatin was not detected. However, in 2 patients with scores of 8 and 9 on the Child-Pugh scale, an increase in systemic exposure was noted, approximately 2 times higher than that of patients with lower Child-Pugh scores. There is no experience with the use of rosuvastatin in patients with a score above 9 on the Child-Pugh scale. Genetic polymorphism: the pharmacokinetics of HMG-CoA reductase inhibitors, including rosuvastatin, also involve transport proteins OATP1B1 and BCRP. In patients with SLCO1B1 (OATP1B1) and/or ABCG2 (BCRP) gene polymorphisms, there is a risk of increased exposure to rosuvastatin. The individual polymorphism of SLCO1B1 c.521CC and ABCG2 c.421AA is associated with a corresponding increase in rosuvastatin exposure (AUC) compared to the SLCO1B1 c.521TT or ABCG2 c.421CC genotypes. In clinical practice, this type of genotyping has not been established, but for patients known to have these types of polymorphisms, a lower daily dose of rosuvastatin is recommended. Children and adolescents: The pharmacokinetic parameters of rosuvastatin in children with familial hypercholesterolemia aged 10 to 17 years have not been fully described. The results of a small pharmacokinetic study of rosuvastatin (involving 18 children) show that the exposure of rosuvastatin in children does not differ from that in adults, and no large deviations in pharmacokinetic parameters are expected depending on the dose. Indications for use Treatment of hypercholesterolemia Primary hypercholesterolemia in adults, children and adolescents 10 years of age and older (type IIa, including familial heterozygous hypercholesterolemia) or mixed dyslipidemia (type IIb) as an adjunct to diet therapy when diet and other non-drug treatments (eg, exercise, weight loss) are not sufficient. Homozygous familial hypercholesterolemia as an adjunct to dietary therapy and other lipid-lowering therapies (eg, LDL apheresis) or in cases where such therapy is not effective enough. Prevention of cardiovascular complications to reduce the risk of severe cardiovascular complications in adult patients without clinical signs of 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). Route of administration and doses Before starting treatment, the patient should follow a standard diet using low-cholesterol foods, which should be continued during the entire period of treatment. Doses Doses of the drug should be selected individually in accordance with the purpose of the treatment and the patient’s therapeutic response to the therapy, taking into account the current generally accepted recommendations for target lipid levels. How to use Inside, at any time of the day, regardless of food intake, do not chew or grind, swallow whole with water. Treatment of hypercholesterolemia The recommended initial dose of the drug is 5 mg or 10 mg 1 time per day for both patients who have not previously taken statins, and for patients transferred to taking this drug after therapy with other HMG-CoA reductase inhibitors. When choosing the initial dose of the drug, one should take into account the cholesterol level in each individual patient, as well as the possible risk of developing cardiovascular complications and the potential risk of side effects. If necessary, the dose can be increased after 4 weeks. Because adverse reactions are more common with the 40 mg dose than with lower doses, titrating up to a maximum of 40 mg should only be done in patients with severe hypercholesterolemia and high cardiovascular risk (particularly those with familial hypercholesterolemia) who failed to achieve the desired result when taking a dose of 20 mg and will be under the supervision of a specialist. Specialist supervision is recommended at the start of the 40 mg dose. Prevention of cardiovascular complications In a study to reduce the risk of cardiovascular events, rosuvastatin was used at a dose of 20 mg per day. Children and adolescents The use of rosuvastatin in children should only be carried out by a specialist. Children and adolescents from 10 to 17 years old (boys – with secondary sexual characteristics on the Tanner scale stage II and above, girls – not earlier than a year after the first menstruation). The usual starting dose for children and adolescents with familial heterozygous hypercholesterolemia is 5 mg per day. The usual dose range is 5-20 mg orally once a day. Dose titration should be carried out individually according to the patient’s therapeutic response to therapy and taking into account tolerability, according to the recommendations for treatment in children and adolescents. Before starting treatment, the patient should follow a standard diet with low cholesterol products, which should be continued during the entire period of treatment. The safety and efficacy of doses greater than 20 mg have not been studied in children. Children under 10 years of age Experience with the use of rosuvastatin in children under 10 years of age is limited. Therefore, Mertenil is not recommended for use in children under 10 years of age. Elderly patients For patients older than 70 years, the recommended initial dose of the drug is 5 mg. Patients with renal insufficiency In patients with mild or moderate renal insufficiency, dose adjustment is not required. The recommended initial dose of the drug is 5 mg for patients with moderate renal insufficiency (CC less than 60 ml / min). The appointment of the drug Mertenil in any doses is contraindicated in patients with severe renal insufficiency (see section “Contraindications” and “Pharmacokinetics”). In patients with moderate renal insufficiency, the use of the drug at a dose of 40 mg is contraindicated. Patients with hepatic insufficiency An increase in the systemic concentration of rosuvastatin in patients with a Child-Pugh score of 7 or below was not detected. However, an increase in the systemic concentration of the drug was observed in patients with Child-Pugh scores of 8 and 9. In such patients, liver function should be monitored during therapy. Data on the use of the drug in patients with a Child-Pugh score above 9 are not available. Mertenil is contraindicated in patients with liver diseases in the active phase. Race In patients of the Mongoloid race, an increase in the systemic concentration of rosuvastatin is possible. When prescribing doses of 10 and 20 mg, the recommended initial dose of the drug for patients of the Mongoloid race is 5 mg. The use of the drug at a dose of 40 mg is contraindicated in such patients. Genetic polymorphisms Certain types of genetic polymorphisms are known to lead to increased exposure to rosuvastatin (see Pharmacokinetics section). For patients known to have these types of polymorphisms, a lower daily dose of rosuvastatin is recommended. Patients predisposed to myopathy For patients predisposed to myopathy, the initial dose of the drug is 5 mg (see section “Precautions”). Concomitant Therapy Rosuvastatin is a substrate for various transport proteins (eg, OATP1B1 and BCRP). When Mertenil 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 (including rhabdomyolysis) (see sections “Precautions” and “Interaction with other drugs”). In such cases, the possibility of prescribing alternative therapy or temporarily stopping Mertenil should be evaluated. If the use of the above drugs and rosuvastatin is necessary, the benefit-to-risk ratio of concomitant therapy should be assessed and the possibility of reducing the dose of Mertenil should be considered (see section “Interaction with other drugs”). Use during pregnancy and lactation Mertenil is contraindicated for use during pregnancy and during breastfeeding. Women of childbearing age should use reliable and adequate contraception. Pregnancy Since cholesterol and cholesterol biosynthetic products are of great importance for fetal development, the potential risk of HMG-CoA reductase inhibition outweighs the benefit of its use during pregnancy. In the event of pregnancy, the drug should be discontinued immediately. Breastfeeding period There are no data on the excretion of rosuvastatin in breast milk. If necessary, the appointment of the drug during lactation, breastfeeding should be stopped. Fertility There are limited data on reproductive toxicity (results from animal studies). PrecautionsRenal effects Proteinuria, predominantly of tubular origin, has been observed in patients receiving high doses of Mertenil, especially 40 mg, but in most cases was intermittent or short-term. It has been shown that such proteinuria does not mean the onset of acute or progression of an existing kidney disease (see section “Side effects”). The incidence of serious renal dysfunction is increased with 40 mg of rosuvastatin. It is recommended to monitor indicators of kidney function during therapy with Mertenil. On the part of the musculoskeletal system When using the drug Mertenil in all dosages, and especially when taking the drug in a dose exceeding 20 mg, myalgia, myopathy and, in rare cases, rhabdomyolysis were detected. Very rarely, rhabdomyolysis has occurred while taking ezetimibe and HMG-CoA reductase inhibitors. In this case, the pharmacodynamic interaction of drugs cannot be excluded, therefore Mertenil and ezetimibe should be used together with caution (see section “Interaction with other drugs”). The frequency of cases of rhabdomyolysis when taking 40 mg of rosuvastatin increases. Determination of creatine phosphokinase Determination of CPK activity should not be carried out after intense physical exertion or in the case of another alternative reason that causes an increase in CPK, as this may make it difficult to interpret the results. With an increase in CPK activity before the start of therapy by more than 5 times the upper limit of normal, a second measurement should be taken after 5-7 days. If repeated measurement confirms the baseline CPK (5 times higher than the upper limit of normal), therapy with Mertenil should not be started. Before starting therapy, Mertenil, like other HMG-CoA reductase inhibitors, should be prescribed with extreme caution to patients with existing risk factors for myopathy / rhabdomyolysis. These factors include: kidney failure; hypothyroidism; own or family history of muscle disease; a history of myotoxicity while taking other HMG-CoA reductase inhibitors or fibrates; alcohol abuse; age over 70; conditions accompanied by an increase in the concentration of the drug in the blood plasma (see sections “Method of application and doses”, “Interaction with other drugs” and “Pharmacokinetics”); simultaneous reception of fibrates. In such patients, the risk-benefit ratio of therapy should be assessed and clinical observation should be carried out throughout the course of therapy. You should not start treatment in case of a significant increase in the baseline CPK (5 times higher than the upper limit of normal). During therapy It is recommended to inform patients 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 or fever! In such patients, it is necessary to monitor the activity of CPK. Treatment should be discontinued if CPK activity is more than 5 times the upper limit of normal or if muscle symptoms are pronounced and cause daily discomfort throughout the day (even if CPK activity is 5 times lower than the upper limit of normal). If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing Mertenil or prescribing an alternative HMG-CoA reductase inhibitor at lower doses with careful monitoring of the patient. Regular monitoring of CPK activity in patients in the absence of symptoms of rhabdomyolysis is not advisable. Very rare cases of immune-mediated necrotizing myopathy, clinically manifested by persistent proximal muscle weakness and an increase in serum creatine kinase activity, have been noted during treatment or after discontinuation of treatment with statins, including rosuvastatin. Additional studies of the muscular and nervous system, serological studies, as well as immunosuppressive therapy may be required. However, an increase in the incidence of myositis and myopathy has been observed in patients taking other HMG-CoA reductase inhibitors in combination with fibric acid derivatives, including gemfibrozil, cyclosporine, lipid-lowering doses of nicotinic acid, azole antifungals, protease inhibitors, and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when co-administered with certain HMG-CoA reductase inhibitors. Therefore, the simultaneous use of rosuvastatin and gemfibrozil is not recommended. The ratio of risk and possible benefit should be carefully assessed when using rosuvastatin with fibrates or nicotinic acid in lipid-lowering doses (more than 1 g). Simultaneous administration of rosuvastatin at a dose of 40 mg and fibrates is contraindicated (see sections “Interaction with other drugs” and “Side effects”). Mertenil should not be administered to patients with acute, severe illness suggestive of myopathy or with possible development of secondary renal failure secondary to rhabdomyolysis (eg, sepsis, hypotension, surgery, trauma, severe metabolic syndrome, uncontrolled seizures, endocrine disorders, electrolyte disturbances (See the “With caution” section.) Effects on the liver Like other inhibitors of HMG-CoA reductase, Mertenil should be used with extreme caution in patients who abuse alcohol or have a history of liver disease. It is recommended that liver function tests be performed before and after 3 month after the start of treatment.If the activity of “liver” transaminases in the blood serum is 3 times the upper limit of normal, you should stop taking the drug Mertenil or reduce the dose taken (see the section “Method of application and doses”).The frequency of severe liver dysfunction (associated , mainly from the top by the activity of “liver” transaminases), increases when taking 40 mg of the drug. In patients with secondary hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of the underlying disease should be carried out before starting treatment with Mertenil. Race In the course of pharmacokinetic studies, an increase in the systemic concentration of rosuvastatin among patients of the Mongoloid race was revealed in comparison with the data obtained among patients – representatives of the Caucasian race (see sections “Method of application and doses”, “Contraindications” and “Pharmacokinetics”). HIV protease inhibitors During the co-administration of rosuvastatin and the combination of various HIV protease inhibitors with ritonavir, an increase in the systemic exposure of rosuvastatin has been observed. Both the benefit of lowering blood lipids while taking rosuvastatin should be carefully evaluated, as well as the possible increase in plasma concentrations of rosuvastatin at the beginning of treatment and during the period of increasing the dose of the drug in patients with HIV taking HIV protease inhibitors. Simultaneous administration with HIV protease inhibitors is not recommended without dose adjustment of rosuvastatin (see sections “Method of application and doses” and “Interaction with other drugs”). Lactose The drug contains lactose and should not be taken by patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption syndrome. Interstitial lung disease When using some statins, especially for a long time, isolated cases of interstitial lung disease have been reported (see section “Side Effects”). Symptoms of the disease may include shortness of breath, non-productive 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 There is evidence that statins, as a class of drugs, cause an increase in blood glucose levels and in some patients at high risk of developing diabetes in the future, they can provoke a level of hyperglycemia, which is indicated by the standard treatment of diabetes mellitus. However, this risk is outweighed by the reduced risk of vascular complications, so there is no reason to stop statin treatment. In patients at risk of hyperglycemia (fasting glucose concentration from 5.6 to 6.9 mmol / l, BMI > 30 kg / m2, elevated triglycerides, arterial hypertension), clinical and biochemical parameters should be monitored in accordance with national recommendations. Children and adolescents aged 10 to 17 years It is known that the effect of rosuvastatin on height, body weight, BMI and the development of secondary sexual characteristics according to the Tanner scale in children and adolescents aged 10 to 17 years was evaluated only for one year. Interactions with other drugs Vitamin K antagonists: as with other HMG-CoA reductase inhibitors, initiation of rosuvastatin therapy or an increase in the dose of the drug in patients receiving concomitant vitamin K antagonists (for example, warfarin or other coumarin anticoagulants), may lead to an increase in international normalized ratio (INR). Cancellation or dose reduction of rosuvastatin may cause a decrease in INR. In such cases, INR monitoring should be carried out. Oral contraceptives/hormone replacement therapy: Simultaneous use of rosuvastatin and oral contraceptives can lead to an increase in the AUC of ethinylestradiol and norgestrel by 26% and 34%, respectively. This increase in plasma concentrations should be taken into account when choosing the dose of oral contraceptives. Pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement therapy drugs are not available, so a similar effect cannot be excluded when using this combination. However, this combination of drugs was widely used by women in clinical trials and was well tolerated. Other medicinal products: based on data from studies of specific interactions, no clinically significant interaction is expected while taking rosuvastatin and digoxin. Children Interaction studies have only been performed in adults. The intensity of interactions in children is unknown. Contraindications hypersensitivity to rosuvastatin or any of the components of the drug; liver disease in the active phase, including a persistent increase in the activity of “liver” transaminases, as well as any increase in the activity of transaminases in the blood serum by more than 3 times compared to the upper limit of normal; severe renal dysfunction (CC less than 30 ml / min); myopathy; simultaneous reception of cyclosporine; pregnancy and breastfeeding period; women of childbearing age who do not use reliable contraceptives; lactose intolerance, lactase deficiency or glucose-galactose malabsorption. The use of rosuvastatin at a dose of 40 mg is contraindicated in patients with factors predisposing to the development of myopathy / rhabdomyolysis. Such factors include: moderately severe renal impairment (creatinine clearance less than 60 ml/min); hypothyroidism; the presence in an individual or family history of hereditary muscle diseases; myotoxicity while taking other inhibitors of HMG-CoA reductase (3-hydroxy-3-methylglutarylcoenzyme A-reductase) or a history of fibrates; alcohol abuse; conditions that can lead to an increase in the concentration of rosuvastatin in the blood plasma; belonging to the Mongoloid race; simultaneous reception of fibrates. Rosuvastatin in all doses, especially at a dose of 40 mg, should be taken with caution in the following cases: there is a risk of developing myopathy / rhabdomyolysis – renal failure, hypothyroidism; a personal or family history of hereditary muscle disease and a previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates; excessive alcohol consumption; conditions in which an increase in the plasma concentration of rosuvastatin was noted; age over 70; a history of liver disease; sepsis; arterial hypotension; extensive surgical interventions; trauma; severe metabolic, endocrine or electrolyte disturbances; uncontrolled epilepsy; race (Mongoloid race); simultaneous reception of fibrates. Composition Each film-coated tablet contains: Active ingredient: Film-coated tablets, 5 mg: rosuvastatin calcium 5.2 mg (equivalent to 5 mg rosuvastatin); Film-coated tablets, 10 mg: rosuvastatin calcium 10.4 mg (equivalent to 10 mg rosuvastatin); 20 mg film-coated tablets: rosuvastatin calcium 20.8 mg (equivalent to 20 mg rosuvastatin). Excipients: Lactose monohydrate, microcrystalline cellulose 12, magnesium hydroxide, crospovidone type A, magnesium stearate. The composition of the film shell: Opadry II white (polyvinyl alcohol, titanium dioxide E171, macrogol 3350, talc). Overdose There is no specific treatment for overdose. In case of overdose, symptomatic treatment and supportive measures are recommended. Liver function and the degree of CPK activity should be monitored. Hemodialysis in this case is probably ineffective. Side effects Side effects associated with taking the drug Mertenil are usually mild and short-lived. In controlled clinical trials, less than 4% of patients treated with rosuvastatin discontinued treatment due to side effects. Based on clinical trial data and extensive post-marketing experience, Table 2 below presents the adverse drug reaction (ADR) profile for rosuvastatin. ADRs are classified by their frequency of occurrence and by organ system classes. The frequency of NLR is presented as follows: often (?1/100 to <1/10); infrequently (?1/1000 to <1/100); rarely (?1/10000 to <1/1000); very rarely (<1/10000); frequency unknown (cannot be estimated from available data). Table 2. Adverse drug reactions Organ system class Common Uncommon Rare Very rare Frequency unknown Blood and lymphatic system disorders Thrombocytopenia Immune system disorders Hypersensitivity reactions, including angioedema Endocrine system disorders Type 2 diabetes mellitus1 Psychiatric disorders Depression disorders from the nervous system Headache Dizziness Polyneuropathy Memory loss Peripheral neuropathy Sleep disorders (including insomnia and nightmares) Respiratory, chest and mediastinal disorders Cough Dyspnea Gastrointestinal disorders Constipation Nausea Abdominal pain Pancreatitis Diarrhea Disorders on the part of the liver and biliary tract Increased activity of "liver" transaminases Jaundice Hepatitis Disorders of the skin and subcutaneous tissues Skin itch Rash Urticaria Stevens-Johnson syndrome Disorders of the musculoskeletal and connective tissue Myalgia Myopathy (including myositis) Rhabdomyolysis Arthralgia Immune-mediated necrotizing myopathy Tendon diseases in some cases complicated by rupture Kidney and urinary tract disorders Hematuria Genital and breast disorders Gynecomastia General dis