Rosart Coated 40mg N90 Tablets
Condition: New product
1000 Items
Rating:
Be the first to write a review!
More info
Active ingredients
Rosuvastatin
Release form
Pills
Composition
Rosuvastatin calcium 41.68 mg;; which corresponds to the content of rosuvastatin 40 mg; Excipients: microcrystalline cellulose (type 102) - 92.4 mg, crospovidone (type A) - 28 mg, calcium hydrogen phosphate dihydrate - 137.2 mg, lactose monohydrate - 253.68 mg, magnesium stearate - 7.04 mg.; Film coating composition: opadry pink II 33G240007 ~ 16.8 mg (hypromellose-2910 - 6.72 mg, titanium dioxide - 4.1765 mg, lactose monohydrate - 3.528 mg, macrogol-3350 - 1.344 mg, triacetin - 1.008 mg, carmine dye red - 0.0235 mg).
Pharmacological effect
Lipid-lowering drug from the group of statins. Selective competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) -reductase - an enzyme that turns HMG-CoA into mevalonate, a precursor of cholesterol.; Increases the number of LDL receptors on the surface of hepatocytes, which leads to increased uptake and catabolism of LDL, inhibition of VLDL synthesis, reducing the total amount of LDL and VLDL. Reduces the increased concentration of LDL cholesterol, non-HDL cholesterol, VLDL cholesterol, total cholesterol, triglycerides (TG), TG-VLDL, apolipoprotein B (ApoB), lowers the ratio of cholesterol-LDL / HDL-cholesterol, total cholesterol-LDL, total cholesterol, low cholesterol-LDL / cholesterol, total cholesterol, low cholesterol , cholesterol-non-HDL / cholesterol-HDL, apoB / apolipoprotein AI (ApoA-I), increases the concentration of HDL-cholesterol and ApoA-I.; The lipid-lowering effect is directly proportional to the size of the dose administered. The therapeutic effect appears within 1 week after the start of therapy, after 2 weeks it reaches 90% of the maximum, reaches its maximum by 4 weeks and remains constant after that. Effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia (regardless of race, gender or age), including in patients with diabetes and familial hypercholesterolemia. In 80% of patients with hypercholesterolemia IIa and IIb type (classification according to Fredrickson) with an average baseline LDL cholesterol-level of about 4.8 mmol / l while receiving the drug in a dose of 10 mg, the concentration of cholesterol-LDL reaches less than 3 mmol / l. In patients with homozygous familial hypercholesterolemia who take the drug at a dose of 20 mg and 40 mg, the average decrease in LDL cholesterol concentration is 22%; an additive effect is observed in combination with fenofibrate (with respect to a decrease in the TG concentration) and with nicotinic acid in lipid-lowering doses ≥ 1 g / day (in relation to increasing the concentration of HDL cholesterol).
Pharmacokinetics
Absorption; Cmax of rosuvastatin in the blood plasma is reached approximately 5 hours after taking the drug. Absolute bioavailability is approximately 20%. Systemic exposure of rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily intake.; Distribution; It penetrates the placental barrier. Rosuvastatin is predominantly absorbed by the liver, which is the main site of cholesterol synthesis and metabolism of LDL-C. Vd - 134 l. Plasma protein binding (predominantly with albumin) is approximately 90%; Metabolism; Biotransformed in the liver to a small extent (about 10%), being a non-core substrate for cytochrome P450 isoenzymes. As in the case of other HMG-CoA reductase inhibitors, a specific membrane carrier, a polypeptide transporting the organic anion (OATP) 1B1, which plays an important role in its hepatic elimination, is involved in the process of hepatic capture of the drug. CYP2C9 is the main isoenzyme involved in rosuvastatin metabolism. CYP2C19, CYP3A4, and CYP2D6 isozymes are less involved in metabolism. The main metabolites of rosuvastatin are N-desmethyl and lactone metabolites. N-desmethyl is about 50% less active than rosuvastatin, lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity on the inhibition of circulating HMG-CoA reductase is provided by rosuvastatin, the rest is provided by its metabolites.; Excretion; About 90% of the dose of rosuvastatin is excreted unchanged through the intestine, and the rest by the kidneys. T1 / 2 - about 19 hours, does not change with increasing dose of the drug. The average plasma clearance is approximately 50 l / h (coefficient of variation is 21.7%); Pharmacokinetics in special groups of patients; In patients with mild and moderate renal insufficiency, the plasma concentration of rosuvastatin or N-desmethyl does not change significantly. In patients with severe renal insufficiency (CC less than 30 ml / min), plasma concentration of rosuvastatin is 3 times higher, and N-desmethyl is 9 times higher than in healthy volunteers. The plasma concentration of rosuvastatin in hemodialysis patients is about 50% higher than in healthy volunteers. Patients with different stages of liver failure with a score of 7 or less on the Child-Pugh scale did not show an increase in T1 / 2 of rosuvastatin; in patients with grades 8 and 9 on the Child-Pugh scale, T1 / 2 lengthening was 2 times.There is no experience of using the drug in patients with more severe liver dysfunction.; Gender and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin.; Pharmacokinetic parameters depend on race: AUC in Japanese and Chinese is 2 times higher than in Europe and North America . In representatives of the Mongoloid race and Indians, the average value of AUC and Cmax increases 1.3 times.
Indications
- primary hypercholesterolemia (type IIa according to Fredrickson, including heterozygous hereditary hypercholesterolemia) or mixed (combined) hyperlipidemia (type IIb according to Fredrickson), as a supplement to the diet and other non-drug measures (exercise and weight loss) ;; hypercholesterolemia with insufficient effectiveness of diet therapy and other types of treatment aimed at reducing the concentration of lipids (for example, LDL-apheresis) or if such types of treatment are not suitable patient ;; - hypertriglyceridemia (type IV according to Fredrikson) 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 cholesterol; -vascular complications (stroke, heart attack, arterial revascularization) 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 The 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 cholesterol, smoking, a family history of early onset of CHD).
Contraindications
For Rosart in a daily dose of 5, 10 and 20 mg: - hypersensitivity to rosuvastatin or other components of the drug ;; - liver disease in the active phase, including a persistent increase in serum activity of hepatic transaminases (more than 3 times compared with VGN) ;; - severe renal dysfunction (CC less than 30 ml / min) ;; - myopathy ;; - simultaneous use of cyclosporine ;; - use in women of reproductive age,not using adequate methods of contraception ;; - pregnancy and breastfeeding period ;; - age up to 18 years (efficacy and safety not established) ;; - lactose intolerance, lactase deficiency, glucose-galactose malabsorption (the product contains lactose monohydrate) ;; Rosart in a daily dose of 40 mg:; - Hypersensitivity to rosuvastatin or other components of the drug ;; - Liver diseases in the active phase, including a persistent increase in the serum activity of hepatic transaminases (more than 3 times compared with VGN) ;; - myopathy ;; - simultaneous use of cyclosporine ;; - use in women of reproductive age who do not use adequate methods of contraception ;; - pregnancy and breastfeeding period ;; - age up to 18 years (efficacy and safety not established) ;; - lactose intolerance, lactase deficiency, glucose-galactose malabsorption (the drug contains lactose monohydrate) ;; - myotoxicity while taking other HMG-CoA reductase inhibitors or fibrates in history ;; - hypothyroidism ;; - renal insufficiency oh or moderate severity (CC less than 60 ml / min) ;; - excessive alcohol consumption ;; - conditions that can lead to an increase in plasma concentration of rosuvastatin ;; - simultaneous use of fibrates ;; - use of patients of the Mongoloid race ;; - family or a personal history of hereditary muscular diseases. With caution; For Rosart, 5, 10, and 20 mg daily doses: risk factors for myopathy and / or rhabdomyolysis - renal failure (CC more than 30 ml / min), hypothyroidism, personal or familial history of inheritance GOVERNMENTAL muscle disease and previous medical history miotoksichnosti when using other HMG-CoA reductase inhibitors or fibrates; excessive drinking, age over 70 years; conditions in which there is an increase in the plasma concentration of rosuvastatin; race (Mongoloid race), simultaneous use with fibrates, history of liver disease, sepsis, arterial hypotension, extensive surgical interventions, injuries, severe metabolic, endocrine or electrolyte disturbances or uncontrolled epilepsy. For the Rosart daily dosage of 40 mg : the presence of risk factors for the development of myopathy and / or rhabdomyolysis - renal failure (QC more than 60 ml / min), age over 70 years, history of liver disease, sepsis, hypotension, extensive chi urgicheskie intervention, trauma, severe metabolic,endocrine or electrolyte disturbances or uncontrolled epilepsy.
Dosage and administration
The drug is taken orally, not chewed or crushed, swallowing whole, squeezed with water, regardless of the time of day and food intake.; Before starting treatment with Rosart, the patient should begin to follow a standard lipid-lowering diet and continue to follow it during treatment. individually, depending on the indications and therapeutic response, taking into account the current generally accepted recommendations for target lipid concentrations. The recommended initial dose of Rosart for patients starting the drug or for patients transferred from receiving other HMG-CoA reductase inhibitors is 5 or 10 mg 1 time / day. When choosing the initial dose, one should be guided by the patient’s cholesterol concentration and take into account the risk of cardiovascular complications, and the potential risk of adverse reactions should be evaluated. If necessary, after 4 weeks the dose of the drug can be increased. Due to the possible development of side effects when taking a dose of 40 mg compared with lower doses of the drug, the final titration to the maximum dose of 40 mg should be carried out only in patients with severe hypercholesterolemia and high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia) in whom the target concentration of cholesterol was not reached when taking a dose of 20 mg and which will be medical supervision;. Recommended especially careful monitoring of patients receiving the drug in a dose of 40 mg. After 2-4 weeks of therapy and / or increasing the dose of the drug, monitoring of lipid metabolism indices is necessary. In elderly patients older than 70 years, the recommended initial dose of Rosart is 5 mg, no other dose adjustment is required.; In patients with hepatic insufficiency, the Child- Drink below 7 points dose adjustment is not required. Patients with a score of 8 and 9 on the Child-Pugh scale should have a preliminary assessment of renal function. The experience of using rosuvastatin in patients with hepatic impairment is higher than 9 on the Child-Pugh scale.Rosuvastatin is contraindicated in patients with liver disease in the active phase. In case of renal failure, mild or moderate severity of dose adjustment is not required. An initial dose of 5 mg is recommended for patients with moderately severe renal insufficiency (CC less than 60 ml / min). For patients with moderate renal insufficiency (CC less than 30-60 ml / min), the administration of the drug in a dose of 40 mg is contraindicated. Rosart is contraindicated in any doses to patients with severe renal failure (CC less than 30 ml / min); In patients of the Mongoloid race, an increase in the systemic concentration of rosuvastatin is possible. The initial recommended dose of the drug for patients of the Mongoloid race is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in such patients.; There are known types of genetic polymorphism, which can lead to an increase in the systemic concentration of rosuvastatin. In patients with identified specific polymorphism, lower daily doses of rosuvastatin are recommended. The initial recommended dose for patients prone to the development of myopathy is 5 mg. The use of the drug at a dose of 40 mg in these patients is contraindicated.; Combination therapy; Rosuvastatin is a substrate for various transport proteins (for example, OATP1B1 and BCRP). The risk of myopathy, including rhabdomyolysis, is increased while taking rosuvastatin with drugs that increase the concentration of rosuvastatin in the blood plasma due to their interaction with transport proteins. This group of substances includes cyclosporine, HIV protease inhibitors, including a combination of ritonavir with atazanavir, lopinavir and / or tipranavir. Whenever possible, a decision should be made on the appointment of alternative therapy and, if necessary, to temporarily stop taking rosuvastatin. In the case where concurrent administration cannot be avoided, the potential risk of interaction and the potential benefits of co-treatment should be carefully assessed.