Rosuvastatin pills 10mg №90

International non-proprietary name: Rosuvastatin

Dosage Form: film coated tablets

Composition:

Dosage 5 mg Active ingredient: Rosuvastatin Calcium in terms of rosuvastatin - 5 mg. Excipients: core - lactose monohydrate (milk sugar) - 32.9 mg; calcium phosphate dihydrate - 5.0 mg; Povidone (medium molecular weight polyvinylpyrrolidone) - 3.0 mg; Croscarmellose sodium (primelloza) - 3.0 mg; sodium stearyl fumarate - 0.8 mg; colloidal silicon dioxide (Aerosil) - 0.3 mg; microcrystalline cellulose - 30.0 mg; shell - Opadry II (polyvinyl alcohol, partially hydrolyzed - 0.88 mg; macrogol (polyethylene glycol) 3350 - 0.247 mg; talc - 0.4 mg; titanium dioxide E 171 - 0.3834 mg; soy lecithin E 322 - 0.07 mg; aluminum lacquer based on indigo carmine dye - 0.0012 mg; aluminum lacquer based on dye azorubine - 0.0102 mg; aluminum lacquer based on dye crimson [Ponso 4R] - 0.0082 mg). Dosage 10 mg Active ingredient: Rosuvastatin calcium in terms of rosuvastatin -10 mg. Excipients: core - lactose monohydrate (milk sugar) - 44.3 mg; calcium phosphate dihydrate - 10.0 mg; Povidone (medium molecular weight polyvinylpyrrolidone) - 6.0 mg; Croscarmellose sodium (primelloza) - 4.0 mg; sodium stearyl fumarate - 1.2 mg; colloidal silicon dioxide (Aerosil) - 0.5 mg; microcrystalline cellulose - 44.0 mg; shell - Opadry II (polyvinyl alcohol,partially hydrolyzed - 1.76 mg; macrogol (polyethylene glycol) 3350 - 0.494 mg; talc - 0.8 mg; titanium dioxide E 171 - 0.7668 mg; soy lecithin E 322 - 0.14 mg; indigo carmine dye-based aluminum varnish - 0.0024 mg; aluminum lacquer based on dye azorubin - 0.0204 mg; crimson dye-based aluminum varnish [Ponso 4R] - 0,0164 mg). Dosage 20 mg Active ingredient: Rosuvastatin calcium in terms of rosuvastatin - 20 mg. Excipients: core - lactose monohydrate (milk sugar) - 67.6 mg; calcium phosphate dihydrate - 20.0 mg; Povidone (medium molecular weight polyvinylpyrrolidone) - 9.0 mg; Croscarmellose sodium (primelloza) - 6.6 mg; sodium stearyl fumarate - 2.0 mg; colloidal silicon dioxide (aerosil) - 0.8 mg; microcrystalline cellulose - 74.0 mg; shell - Opadry II (polyvinyl alcohol, partially hydrolyzed - 2.64 mg; macrogol (polyethylene glycol) 3350 - 0.741 mg; talc - 1.2 mg; titanium dioxide E 171 - 1.1502 mg; soy lecithin E 322 - 0.21 mg; aluminum lacquer based on indigo carmine dye - 0.0036 mg; aluminum lacquer based on dye azorubine - 0.0306 mg; aluminum lacquer based on dye crimson [Ponso 4R] - 0.0246 mg). Dosage 40 mg Active ingredient: Rosuvastatin calcium in terms of Rosuvastatin - 40 mg. Excipients: core - lactose monohydrate (milk sugar) - 55.2 mg; calcium phosphate dihydrate - 40.0 mg; Povidone (medium molecular weight polyvinylpyrrolidone) - 13.0 mg; croscarmellose sodium (primelloza) - 8.3 mg; sodium stearyl fumarate - 2.5 mg; colloidal silicon dioxide (Aerosil) - 1.0 mg; microcrystalline cellulose - 90.0 mg; shell - Opadry II (polyvinyl alcohol,partially hydrolyzed - 3.52 mg; macrogol (polyethylene glycol) 3350 - 0.988 mg; talc - 1.6 mg; titanium dioxide E 171-1.5336 mg; soy lecithin E 322 - 0.28 mg; indigo carmine dye-based aluminum lacquer - 0.0048 mg; aluminum lacquer based on dye azorubine - 0.0408 mg; crimson dye-based aluminum varnish [Ponso 4R] - 0.0328 mg).

Description

Tablets, film-coated pink, round, biconvex. In cross section, the core of the pill is white or almost white.

Pharmacotherapeutic group of the drug:

hypolipidemic agent - HMG-CoA reductase inhibitor

Pharmacological properties Pharmacodynamics The mechanism of action Rosuvastatin is a selective, competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonic acid, a precursor of cholesterol. The main target of rosuvastatin action is the liver, where cholesterol (cholesterol) synthesis and low density lipoprotein catabolism (LDL) are performed. Rosuvastatin increases the number of “hepatic” LDL receptors on the cell surface, increasing the uptake and catabolism of LDL, which in turn leads to inhibition of the synthesis of very low density lipoproteins (VLDL), thereby reducing the total number of LDL and VLDL. Pharmacodynamics Rosuvastatin-SZ lowers elevated concentrations of LDL cholesterol (LDL-C), total cholesterol, triglycerides (TG), increases the concentration of high-density cholesterol-HDL-C, and also lowers the concentrations of apolipoprotein B (ApoV), LDL-HDL, HS-VLDLTG-VLDL and increases the concentration of apolipoprotein AI (ApoA-I), reduces the ratio of cholesterol-LDL / cholesterol-HDL cholesterol, total cholesterol-cholesterol-HDL cholesterol and cholesterol-cholesterol-HDL cholesterol and the ratio of apoV / apoA I. The therapeutic effect develops within one week after the start of therapy with Rosuvastatin-SZ, after 2 weeks of treatment it reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved by the 4th week of therapy and is maintained with regular use of the drug. Rosuvastatin-SZ is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia, regardless of race, gender, or age, including patients with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with hypercholesterolemia IIa and IIb type according to Fredrikson (the average initial concentration of LDL-C is about 4.8 mmol / l) while receiving the drug at a dose of 10 mg, the concentration of LDL-C makes up less than 3 mmol / l. In patients with heterozygous familial hypercholesterolemia who received Rosuvastatin-SZ at a dose of 20-80 mg, there is a positive trend in lipid profile parameters. After titration to a daily dose of 40 mg (12 weeks of therapy), a decrease in the concentration of LDL-C by 53% is noted. 33% of patients achieved a ChL-LDL concentration of less than 3 mmol / L. In patients with homozygous familial hypercholesterolemia, taking Rosuvastatin-SZ at a dose of 20 mg and 40 mg, the average decrease in the concentration of LDL-C is 22%.

In patients with hypertriglyceridemia with an initial TG concentration of 273 to 817 mg / dL, treated with Rosuvastatin-SZ at a dose of 5 mg to 40 mg once a day for 6 weeks, the plasma TG concentration significantly decreased. An additive effect is observed in combination with fenofibrate in relation to the content of triglycerides and with nicotinic acid in lipid-lowering doses in relation to the content of cholesterol-HDL (see also the section "Special Instructions"). According to the results of clinical studies, patients with severe hypercholesterolemia and a high risk of cardiovascular diseases (CVD) should be prescribed a dose of the drug Rosuvastatin-SZ 40 mg. The results of a clinical study (Justification of the use of statins for primary prophylaxis: an interventional study assessing rosuvastatin) showed that rosuvastatin significantly reduced the risk of developing cardiovascular complications. Pharmacokinetics Absorption and distribution The maximum concentration of rosuvastatin in the blood plasma is reached approximately 5 hours after ingestion. Absolute bioavailability is approximately 20%. Rosuvastatin is metabolized mainly by the liver, which is the main site of cholesterol synthesis and metabolism of LDL-C. The volume of distribution of rosuvastatin is approximately 134 liters. Approximately 90% of rosuvastatin binds to plasma proteins, mainly albumin. Metabolism Exposed to limited metabolism (about 10%).Rosuvastatin is a non-core substrate for metabolism by cytochrome P450 enzymes. The main isoenzyme involved in rosuvastatin metabolism is the CYP2C9 isoenzyme. The isoenzymes CYP2C19, CYPZA4 and CYP2D6 are less involved in metabolism. The main identified metabolites of rosuvastatin are N-desme-tilrozuvastatin and lactone metabolites. N-desmethylrosuvastatin is approximately 50% less active than rosuvastatin, lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity on inhibition of circulating HMG-CoA reductase is provided by rosuvastatin, the rest is provided by its metabolites. Removal About 90% of the dose of rosuvastatin is excreted unchanged through the intestines (including absorbed and unabsorbed rosuvastatin). The rest is excreted by the kidneys. The plasma half-life (T1 / 2) is approximately 19 hours. The half-life 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 HMG-CoA reductase inhibitors, membrane cholesterol transporter, which plays an important role in the hepatic elimination of rosuvastatin, is involved in the hepatic uptake of rosuvastatin. Linearity Systemic exposure of rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily intake. Special populations of patients. Age and gender Gender and age do not have a clinically significant effect on rosuvastatin pharmacokinetics. Ethnic groups Pharmacokinetic studies showed an approximately twofold increase in the AUC median (area under the concentration-time curve) and Cmax (rosus plasma concentration) of rosuvastatin in Mongoloid patients (Japanese, Chinese, Filipinos, Vietnamese, and Koreans) compared with Europeans; Hindus showed an increase in the median AUC and C max by 1.3 times. Pharmacokinetic analysis revealed no clinically significant differences in pharmacokinetics among Caucasians and representatives of the Negroid race. Renal failure In patients with mild and moderate renal insufficiency, the plasma concentration of rosuvastatin or N-desmethylrosis-vastatin does not change significantly. In patients with severe renal insufficiency (creatinine clearance (CC) less than 30 ml / min.), Plasma plasma concentration of rosuvastatin is 3 times higher, and the concentration of N-desmethylrozuvastatin is 9 times higher than in healthy volunteers. The plasma concentration of rosuvastatin in hemodialysis patients was about 50% higher than in healthy volunteers. Liver failure In patients with various stages of liver failure, no increase in the half-life of rosuvastatin was detected in patients with 7 points and lower on the Child-Pugh scale. Two patients with 8th and 9th grades on the Child-Pugh scale showed an increase in the half-life of at least 2 times. Experience with rosuvastatin in patients with more than 9 points on the Child-Pugh scale is absent.

Indications for use

Fredrikson's primary hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as a supplement to the diet when diet and other non-drug therapies (eg, exercise, weight loss) are insufficient. - Familial homozygous hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (for example, LDL-apheresis), or in cases when such therapy is not effective enough. - Hypertriglyceridemia (type IV by Fredrikson) as a supplement to the diet. - Primary dysbetalipoproteinemia (type III according to Frederickson) as a supplement to the diet. - To slow the progression of atherosclerosis as a supplement to the diet in patients who have been shown therapy to reduce the concentration of total cholesterol and LDL-C. - Primary prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary artery disease, but with an increased risk of its development (women older than 50 years for men and older than 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 hypertension, low concentration of HDL-C, smoking, family history of early onset of CHD).

Contraindications

For the drug Rosuvastatin-SZ in a daily dose of 5 mg, 10 mg and 20 mg: - hypersensitivity to rosuvastatin or any of the components of the drug - lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose) - children under 18 years of age - liver disease in the active phase, including a persistent increase in serum transaminase activity and any increase transaminase activity in the blood serum (more than 3 times compared with the upper limit of the norm) - severe renal failure (CC less than 30 ml / min) - myopathy - simultaneous administration of cyclosporine - in women n: pregnancy; breastfeeding period, lack of adequate methods of contraception - increased concentration of creatine phosphokinase (CPK) in the blood is more than 5 times compared with the upper limit of the norm - combined use with HIV protease inhibitors - patients prone to the development of myotoxic complications For the drug Rosuvastatin-SZ in a daily dose of 40 mg: - hypersensitivity to rosuvastatin or any of the components of the drug - lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose) - children under 18 years of age - simultaneous use of cyclosporine - in women: pregnancy, breastfeeding period, lack of adequate contraception - an increase in the concentration of creatine phosphokinase (CPK) in the blood by more than 5 times compared with the upper limit of the norm - combined use with HIV protease inhibitors - renal failure moderate and severe (CC less than 60 ml / min.) - liver disease in the active phase,including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times higher than the upper limit of normal) for patients with risk factors for myopathy / rhabdomyolysis, namely: - hypothyroidism - mytoxicity while taking other HMG inhibitors History of CoA reductase or fibrates - excessive alcohol use - conditions that can lead to an increase in plasma concentration of rosuvastatin - simultaneous use of fibrates - myopathy - personal or family Amnesia muscular disorders - patients Mongoloid With care For the drug Rosuvastatin-SZ in a daily dose of 5 mg, 10 mg and 20 mg: The risk of myopathy / rhabdomyolysis development - renal insufficiency, hypothyroidism, personal or family history of hereditary muscular diseases and a previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates; excessive drinking; age over 65; conditions in which there is an increase in the plasma concentration of rosuvastatin; race (mongoloid race); simultaneous administration with fibrates (see Pharmacokinetics section); history of liver disease; sepsis; hypotension; extensive surgical intervention, trauma, severe metabolic, endocrine or electrolyte disturbances, or uncontrolled convulsive seizures.Simultaneous use with colchicine and ezetimibe (see section "Interaction with other drugs"). For the drug Rosuvastatin-SZ in a daily dose of 40 mg: Renal failure mild (CC more than 60 ml / min); age over 65; history of liver disease; sepsis; hypotension; extensive surgical intervention, trauma, severe metabolic, endocrine or electrolyte disturbances, or uncontrolled convulsive seizures. Simultaneous use with colchicine and ezetimibe (see section "Interaction with other drugs"). Patients with liver failure There is no data or experience with the use of the drug in patients with more than 9 points on the Child-Puy scale (see the sections "Pharmacodynamics" and "Special Instructions").

Use during pregnancy and during breastfeeding

Rosuvastatin-SZ is contraindicated during pregnancy and during breastfeeding. Women of reproductive age should use adequate methods of contraception. Since cholesterol and other cholesterol biosynthesis products are important for fetal development, the potential risk of inhibition of HMG-CoA reductase exceeds the benefits of using the drug in pregnant women. In the event of pregnancy during therapy, the drug should be discontinued immediately. Data regarding the allocation of rosuvastatin with breast milk are not available, so during the period of breastfeeding the drug should be discontinued (see "Contraindications").

Dosage and administration

Inside, do not chew or crush the pill, swallow whole, washed down with water. The drug can be administered at any time of the day, regardless of the meal. Before starting therapy with Rosuvastatin-SZ, the patient should begin to follow the standard cholesterol-lowering diet and continue to follow it during treatment. The dose of the drug should be chosen individually depending on the goals of therapy and the therapeutic response to treatment, taking into account the current recommendations on target lipid concentrations. The recommended initial dose for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, should be 5 mg or 10 mg of Rosuvastatin-SZ 1 time per day. When choosing the initial dose, one should be guided by the individual cholesterol content and take into account the possible risk of cardiovascular complications, as well as the potential risk of side effects. If necessary, the dose can be increased to a maximum after 4 weeks (see the Pharmacodynamics section). In connection with the possible development of side effects when taking a dose of 40 mg, compared with lower doses of the drug (see the “Side Effects” section), increasing the dose to 40 mg after an additional dose of the drug is higher than the recommended initial dose within 4 weeks treatment, can be performed only in patients with severe hypercholesterolemia and at high risk of cardiovascularcomplications (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 (see section "Special instructions"). Especially careful monitoring of patients receiving the drug at a dose of 40 mg is recommended. It is not recommended to prescribe a dose of 40 mg to patients who have not previously visited a doctor. After 2-4 weeks of therapy and / or with increasing doses of the drug Rosuvastatin-SZ, monitoring of lipid metabolism indices is necessary (if necessary, dose adjustment is necessary). Homozygous hereditary hypercholesterolemia The recommended initial dose is 20 mg once a day. Elderly patients Patients over the age of 65 are advised to start using the drug with a dose of 5 mg once a day. Patients with renal failure In patients with mild to moderate renal insufficiency, dose adjustment is not required. In patients with severe renal failure (CC less than 30 ml / min.), The use of the drug Rosuvastatin-SZ is contraindicated. The use of the drug in a dose of 40 mg is contraindicated in patients with moderately impaired renal function (CC 30-60 ml / min.) (See sections "Special instructions" and "Pharmacodynamics"). Patients with moderate renal impairment are recommended an initial dose of 5 mg. Patients with liver failure Rosuvastatin-SZ is contraindicated in patients with liver diseases in the active phase (see section "Contraindications"). Special populations. Ethnic groups When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, there was an increase in the systemic concentration of rosuvastatin among Japanese and Chinese (see the section "Special Instructions"). This fact should be taken into account when prescribing Rosuvastatin-SZ to these groups of patients. When prescribing doses of 10 mg and 20 mg, the recommended starting dose for patients of the Mongoloid race is 5 mg. The prescription of the drug in a dose of 40 mg to patients of the Mongoloid race is contraindicated (see section “Contraindications”). Patients predisposed to myopathy The prescription of the drug in a dose of 40 mg is contraindicated in patients with factors that may indicate a predisposition to the development of myopathy (see the “Contraindications” section). When prescribing doses of 10 mg and 20 mg, the recommended initial dose for this group of patients is 5 mg (see section “Contraindications”). Application with concomitant therapy With simultaneous use of the drug with gemfibrozil, fibrates, nicotinic acid in a dose of more than 1 g / day, an initial dose of 5 mg is recommended for patients. The dose of Rosuvastatin-SZ should not exceed 10 mg once a day.

Side effect

Side effects observed when taking the drug Rosuvastatin-SZ, usually expressed slightly and pass on their own. As with the use of other inhibitors of HMG-CoA reductase, the frequency of occurrence of side effects is mainly dose-dependent.The frequency of adverse effects is as follows: often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000), the frequency is unknown (according to the available data it is not possible to establish the frequency of occurrence), including individual messages. The immune system Seldom: hypersensitivity reactions, including angioedema. Endocrine system Often: type 2 diabetes From the side of the central nervous system Often: headache, dizziness From the digestive tract Often: constipation, nausea, abdominal pain Rarely: pancreatitis On the part of the skin Infrequently: pruritus, rash, urticaria From the musculoskeletal system Often: myalgia Rarely: myopathy (including myositis), rhabdomyolysis Other Often: asthenic syndrome From the urinary system Patients treated with Rosuvastatin-SZ may have proteinuria. Changes in the amount of protein in the urine (from the absence or trace amounts to ++ or more) are observed in less than 1% of patients receiving 10–20 mg of the drug, and in about 3% of patients receiving 40 mg of the drug. A slight change in the amount of protein in the urine was noted when taking a dose of 20 mg. In most cases, proteinuria diminishes or disappears during therapy and does not mean the onset or the progression of an existing kidney disease. From the musculoskeletal system When using the drug Rosuvastatin-SZ in all doses and, especially when taking doses of the drug in excess of 20 mg, the following effects on the musculoskeletal system were reported: myalgia, myopathy (including myositis), in rare cases - rhabdomyolysis with acute renal insufficiency with or without her. A dose-dependent increase in the activity of creatine phosphokinase (CPK) is observed in an insignificant number of patients taking rosuvastatin. In most cases, it was minor, asymptomatic and temporary. In the case of increased activity of CPK (more than 5 times compared with the upper limit of the norm), therapy should be suspended (see the section "Special Instructions"). Liver With the use of rosuvastatin, a dose-dependent increase in the activity of liver transaminases is observed in a small number of patients. In most cases, it is insignificant, asymptomatic and temporary. Laboratory values When using the drug Rosuvastatin-SZ, the following changes in laboratory parameters were also observed: an increase in the concentration of glucose, bilirubin, the activity of gamma-glutamyl transpeptidase, alkaline phosphate, and dysfunction of the thyroid gland. Post-marketing application The following side effects have been reported in the post-marketing use of Rosuvastatin-SZ: From the digestive tract Very rarely: jaundice, hepatitis. Rarely: increased activity of hepatic transaminases.Frequency unknown: diarrhea, fatal and non-fatal liver failure From the musculoskeletal system Very rare: arthralgia. Frequency unknown: immune-mediated necrotizing myopathy From the side of the central nervous system Very rare: polyneuropathy, forgetfulness, amnesia, memory loss, confusion On the part of the respiratory system Frequency unknown: cough, shortness of breath From the urinary system Very rare: hematuria, microhematuria From the skin and subcutaneous fat Frequency unknown: Stevens-Johnson syndrome Reproductive system and mammary gland Frequency unknown: gynecomastia Other Frequency unknown: peripheral edema; thrombocytopenia; interstitial lung disease. When using some statins, the following side effects were reported: depression, sleep disorders, including insomnia and nightmares, sexual dysfunction.

Overdose

When several daily doses are taken simultaneously, the pharmacokinetic parameters of rosuvastatin do not change. There is no specific treatment for an overdose of rosuvastatin. In case of overdose, it is recommended to carry out symptomatic treatment and measures aimed at maintaining the functions of vital organs and systems. The control of liver function and the level of CPK is necessary. It is unlikely that hemodialysis will be effective.

Interaction with other drugs

Cyclosporine: with simultaneous use of rosuvastatin and cyclosporine, AUC of rosuvastatin was, on average, 7 times higher than that observed in healthy volunteers (see the “Contraindications” section). The combined use leads to an increase in the concentration of rosuvastatin in the blood plasma 11 times. It does not affect the plasma concentration of cyclosporine. Indirect anticoagulants: starting therapy with rosuvastatin or increasing the dose of the drug in patients who receive both indirect anticoagulants (for example, warfarin) may lead to an increase in prothrombin time (international normalized ratio - INR). Canceling rosuvastatin or reducing the dose of a drug can lead to a decrease in INR. In such cases, it is recommended