Rosart coated pills 20mg N30
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Active ingredients
Rosuvastatin
Release form
Pills
Composition
Rosuvastatin calcium 20.84 mg, which corresponds to the content of rozuvastatin 20 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 converts HMG-CoA to 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 synthesis of VLDL, reducing the total number 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. Hypolipidemic action 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, taking the drug at a dose of 20 mg and 40 mg, the average decrease in LDL cholesterol concentration is 22%. The additive effect is observed in combination with fenofibrate (in relation to a decrease in TG concentration) and with nicotinic acid in lipid-lowering doses ≥1 g / day (in relation to increasing the concentration of HDL cholesterol).
Pharmacokinetics
Rosuvastatin Cmax absorption in 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 Penetrates through 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 is 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 isoenzymes 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 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, the rest is excreted 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 moderately severe 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 pronounced hepatic dysfunction. Sex and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin. The 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 classification), including heterozygous hereditary hypercholesterolemia or mixed (combined) hyperlipidemia (type IIb according to Fredrickson classification), as a supplement to the diet and other non-drug measures (exercise and weight loss). with insufficient efficacy 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 for the patient. Hypertriglyceridemia (type IV according to Fredrickson's classification) 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 lower total cholesterol and LDL cholesterol. Primary prevention of basic heart disease vascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary heart disease (CHD), but with an increased risk of its development (age t over 50 years old for men and over 60 years old for women, increased C-reactive protein concentration (≥ 2 mg / l) with at least one of the additional risk factors such as arterial hypertension, low HDL cholesterol, smoking, family history of early onset CHD).
Contraindications
Hypersensitivity to rosuvastatin or other components of the drug; Liver disease in the active phase, including a persistent increase in serum activity of liver transaminases (more than 3 times compared to the upper limit of normal (VGN)); Severe renal dysfunction (CC less than 30 ml / min); 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 in lactose intolerance, lactase deficiency, glucose-galactose malabsorption (the product contains lactose monohydrate).
Precautionary measures
Do not exceed recommended doses.
Use during pregnancy and lactation
Rosart is contraindicated during pregnancy and lactation. Use of Rosart in women of reproductive age is possible only if reliable contraceptive methods are used and if the patient is aware of the potential risk of treatment for the fetus. the risk of inhibition of HMG-CoA reductase exceeds the benefits of using the drug during pregnancy. If pregnancy is diagnosed during Rosart therapy, the drug should be immediately discontinued, and patients should be warned of the potential risk to the fetus. There are no data on the release of rosuvastatin with breast milk, so if you need to use the drug during lactation, given the possibility of adverse events infants should decide on the termination of breastfeeding.
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. 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 may be increased. Due to the possible development of side effects when taking a dose of 40 mg compared with lower doses of the drug,final titration to a maximum dose of 40 mg should be carried out only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia) in whom the target cholesterol concentration was not reached when taking a dose of 20 mg be under medical supervision. It is recommended that patients receiving the drug at a dose of 40 mg be especially closely monitored. After 2-4 weeks of therapy and / or increasing the dose of the drug, monitoring of lipid metabolism indices is necessary. In elderly patients over 70 years old, the recommended initial dose of Rosart is 5 mg, and no other dose adjustment is required. In patients with liver failure, the Child-Pugh scale is lower 7 points dose adjustment of the drug 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 varieties 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 predisposed 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 Rozuvastatin 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.
Side effects
According to clinical studies of rosuvastatin, as well as data from its post-marketing use, the following adverse reactions were observed in patients. The frequency of adverse reactions is distributed as follows: very often (more than 1/10); often (from greater than 1/100 to less than 1/10); infrequently (from greater than 1/1000 to less than 1/100); rarely (from greater than 1/10 000 to less than 1/1000); very rarely (from less than 1/10 000); frequency is unknown (according to available data it is impossible to establish the frequency of occurrence). From the blood and lymphatic system: rarely - thrombocytopenia. From the nervous system: often - headache, dizziness, asthenic syndrome; very rarely - polyneuropathy, loss of memory; frequency is unknown - depression, peripheral neuropathy, sleep disturbances, including insomnia and nightmares. On the digestive system: often - constipation, nausea, abdominal pain; rarely - pancreatitis; very rarely - hepatitis, jaundice; frequency unknown - diarrhea. On the part of the respiratory system: frequency unknown - cough, shortness of breath, interstitial lung disease. On the part of the endocrine system: often diabetes mellitus 1. On the part of the musculoskeletal system: often - myalgia; rarely - myopathy (including myositis), rhabdomyolysis; very rarely - arthralgia; frequency unknown - immune necrotizing myopathy; tendon lesionssometimes with ruptures. Allergic reactions: infrequently - pruritus, rash, urticaria; rarely - hypersensitivity reactions, including angioedema. From the skin and subcutaneous tissues: frequency unknown - Stevens-Johnson syndrome. From the urinary system: very rarely - hematuria. From the genitals and mammary gland: very rarely - gynecomastia. From the side laboratory parameters: rarely - a transient increase in AST and ALT activity. Other: frequency unknown - peripheral edema. 1 Frequency depends on the presence of risk factors (fasting blood glucose ≥5.6 mmol / l, BMI is greater than 30 kg / m2, increased concentration of TG, arterial hypertension in history). As with the use of other HMG-CoA reductase inhibitors, the incidence of adverse reactions is dose-dependent, the side effects are usually slightly pronounced and disappear. The effects on kidney function of patients treated with rosuvastatin are urinalysis test strip was detected proteinuria, mainly tubular. Changes in the amount of protein in the urine (from the absence or trace amounts to ++ or more) were observed in less than 1% of patients receiving 10-20 mg of rosuvastatin, and in approximately 3% of patients receiving 40 mg of rosuvastatin. A slight change in the amount of protein in the urine (from the absence or trace amounts to +) was observed when taking a dose of 20 mg. In most cases, proteinuria decreases or disappears during therapy and does not mean the onset or the progression of existing kidney disease. Hematuria was observed in patients receiving rosuvastatin, the available data showed a low incidence of this undesirable reaction. Effect on the musculoskeletal system and, especially when taking doses in excess of 20 mg, it has been reported about the development of myalgia, myopathy, including myositis, in rare cases of rhabdomyolysis with the development of acute renal failure or without it. When taking rosuvastatin, a dose-dependent increase in CPK activity was observed. In most cases, it was minor, asymptomatic and temporary. In the case of increased activity of CPK (more than 5 times compared to VGN), therapy should be suspended. Effect on liver function In a small number of patients with rosuvastatin, there is a dose-dependent increase in liver transaminase activity.In most cases, it is small, asymptomatic, and temporary. When using certain HMG-CoA reductase inhibitors, sexual dysfunction was observed, isolated cases of interstitial lung disease were recorded.
Overdose
When several daily doses are taken simultaneously, the pharmacokinetic parameters of rosuvastatin do not change. Treatment: There is no specific treatment, symptomatic therapy and measures aimed at maintaining the function of vital organs and systems under the control of liver function and CPK activity are performed. It is unlikely that hemodialysis will be effective.
Interaction with other drugs
Transport protein inhibitors Rozuvastatin is a substrate of several transport proteins, including the OATP1B1 membrane transporter involved in the process of hepatic uptake, and the BCRP transport protein. Simultaneous administration of rosuvastatin with drugs that inhibit these transport proteins may increase the plasma concentration of rosuvastatin and increase the risk of myopathy. Simultaneous use of rosuvastatin and cyclosporine does not affect the plasma concentration of cyclosporine, but it increases the effect of rosuvastatin (its elimination slows down, the AUC increases 7 times, Cmax - 11 times). Simultaneous administration of cyclosporine and rosuvastatin is contraindicated. Simultaneous administration of erythromycin and rosuvastatin reduces the AUC of rosuvastatin by 20% and increases Cmax by 30%. Such an interaction may occur as a result of increased intestinal motility caused by taking erythromycin. Patients receiving indirect anticoagulants (for example, warfarin) are recommended to monitor MHO, since initiation of rosuvastatin therapy or an increase in its dose may lead to an increase in MHO and withdrawal of rosuvastatin or a decrease in its dose can lead to its decrease. Gemfibrozil and other lipid-lowering drugs: simultaneous administration of gemfibrozil and rosuvastatin increases Cmax and AUC of rosuvastatin by 2 times. Based on data on specific interactions, pharmacokinetically significant interactions with fenofibrate are not expected; pharmacodynamic interactions are possible. Gemfibrozil, fenofibrate, other fibrates and hypolipidemic doses of nicotinic acid (at least 1 g / day) increased the risk of myopathy while being used with other HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy and when used in as monotherapy.While taking rosuvastatin with one of the drugs in this group, an initial dose of rosuvastatin 5 mg is recommended for patients, the daily dose of rosuvastatin 40 mg is contraindicated in this case. Simultaneous use of rosuvastatin and antacids containing aluminum and magnesium hydroxide reduces the plasma concentration of rosuvastatin by about 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. Simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively, which should be considered when selecting the dose of oral contraceptives. Pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement therapy are not available, therefore, a similar effect cannot be excluded when they are used together. However, this combination was widely used during the clinical trials of rosuvastatin and was well tolerated by patients. The results of in vivo and in vitro studies showed that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. Rosuvastatin is a non-core substrate for these isoenzymes. There was no clinically significant interaction with drugs such as fluconazole (an inhibitor of CYP2C9 and CYP3A4 isoenzymes), ketoconazole (an inhibitor of CYP2A6 and CYP3A4 isoenzymes) associated with the cytochrome P450 system of metabolism. an increase in AUC of rosuvastatin 1.2 times. However, pharmacodynamic interactions between rosuvastatin and ezetimibe cannot be ruled out with regard to the occurrence of adverse events.
special instructions
The effect on kidney function of patients who received high doses of rosuvastatin (mainly 40 mg), in the course of urinalysis, test-stripes showed tubular proteinuria, which in most cases was transient. Such proteinuria did not indicate acute kidney disease or progression of kidney disease. The frequency of reports of serious kidney side reactions in the post-marketing period was higher in patientswho took rosuvastatin at a dose of 40 mg. When using Rosart at a dose of 40 mg, it is recommended to monitor indicators of renal function during treatment. Effect on the musculoskeletal system , myopathies and in rare cases about rhabdomyolysis. In very rare cases, the development of rhabdomyolysis has been reported with simultaneous use of HMG-CoA reductase inhibitors and ezetimibe. In this case, pharmacodynamic interactions cannot be excluded, therefore care should be taken when taking them together. As with other HMG-CoA reductase inhibitors, the frequency of messages in the postmarketing observation of the development of rhabdomyolysis associated with taking rosuvastatin was higher with a 40 mg dose. Determination of CFCO increase its activity, which can lead to incorrect interpretation of the results. If the initial activity of CPK is significantly increased, after 5-7 days it is necessary to re-measure - do not start therapy, if the repeated test confirms the initial activity of CPK (5 times higher than the norm). as well as the appointment of other HMG-CoA reductase inhibitors, patients with existing risk factors for the development of myopathy / rhabdomyolysis. It is necessary to consider the ratio of the expected benefit from therapy and the potential risk and conduct clinical observation throughout the course of treatment. If the initial activity of CPK is significantly increased (5 times higher than VGN), then you should not start treatment with the drug. During treatment, the patient should be informed about the need to immediately inform the doctor about cases of sudden muscle pain, muscle weakness or spasms, especially in combination with malaise and fever. In such patients, the activity of CPK should be determined. Therapy should be discontinued if the activity of CPK is significantly increased (more than 5 times as compared with VGN) or if the muscular symptoms are pronounced and cause daily discomfort (even if the activity of KFK is 5 times less as compared with VGN).If the symptoms disappear and the activity of CPK returns to normal, consideration should be given to reappointment of Rosart or other HMG-CoA reductase inhibitors in smaller doses with careful monitoring of the patient. Routine monitoring of CPK activity in the absence of symptoms is impractical. Very rare cases of immune-mediated necrotizing myopathy with clinical manifestations in the form of persistent proximal muscle weakness and increased serum CPK activity during treatment or discontinuation of statins, including, have been noted. Rosuvastatin. There are no signs of an increase in the effect on skeletal muscles when taking rosuvastatin and concomitant therapy. However, an increase in the incidence of myositis and myopathy was reported in patients taking other HMG-CoA reductase inhibitors in combination with fibrin acid derivatives (including gemfibrozil), cyclosporine, nicotinic acid in lipid-lowering doses ≥1 g / day, azole antifungal agents, inhibitors proteases and macrolide antibiotics. Gemfibrozil increases the risk of myopathy while taking it with some HMG-CoA reductase inhibitors, therefore the simultaneous use of gemfibrozil and rosuvastatin is not recommended. It is necessary to carefully weigh the ratio of the expected benefit and potential risk with the combined use of Rosart and fibrates or nicotinic acid in lipid-lowering doses ≥1 g / day. Taking Rosart at a dose of 40 mg is contraindicated simultaneously with fibrates. During treatment, especially during the dose adjustment period Rosart, every 2-4 weeks should be monitored lipid profile and according to him, if necessary, change the dose of the drug. The drug Rozart should not be taken by patients with the manifestation of acute and severe x symptoms of myopathy or with the presence of risk factors predisposing to the development of renal dysfunction and secondary rhabdomyolysis (for example, sepsis, arterial hypotension, extensive surgical interventions, injuries, severe metabolic disorders, severe endocrine disorders and severe disorders of water and electrolyte balance, uncontrolled seizures) Effects on Liver Function As other inhibitors of HMG-CoA reductase, rosuvastatin should be used with caution in patients who abuse alcohol and / or with illnesses. iem liver history. It is recommended to determine the indicators of liver function before the start of therapy and 3 months after the start of therapy.Taking Rosart should stop or reduce the dose of the drug, if the level of serum hepatic transaminase activity is 3 times higher than VGN.Patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome should be treated before Rosart. With post-marketing follow-up of rosuvastatin, the frequency of reports of the development of severe liver dysfunction (expressed mainly in elevated liver transaminases) was higher with a 40 mg dose. -proteaseIn the joint administration of rozuvastatin and a combination of various HIV protease inhibitors with ritonavir, magnification of systemic concentration of rosuvastatin. The decrease in blood lipid concentration should be carefully evaluated, as well as the possible increase of rosuvastatin in the blood plasma at the beginning of treatment and during the period of increasing the dose of Rosart in patients with HIV taking HIV protease inhibitors. Simultaneous administration of HIV protease inhibitors is not recommended without dose adjustment of rosuvastatin. Interstitial lung disease With the use of some HMG-CoA reductase inhibitors, especially for a long time, isolated cases of interstitial lung disease have been reported. Manifestations of the disease can be shortness of breath, unproductive cough and worsening of general well-being (weakness, weight loss and fever). If interstitial lung disease is suspected, therapy with HMG-CoA reductase inhibitors should be discontinued. Type 2 diabetes Some data suggest that HMG-CoA reductase inhibitors increase blood glucose concentrations and increase the likelihood of developing type 2 diabetes in some patients. However, this risk is outweighed by the ability of HMG-CoA reductase inhibitors to reduce the risk of developing vascular complications, so this fact is not a reason to interrupt the treatment with rosuvastatin. It is necessary to establish clinical observation and conduct a biochemical blood test according to national standards in patients at risk of developing hyperglycemia (blood glucose concentration 5.6–6.9 mmol / l, BMI is greater than 30 kg / m2, triglyceridemia, arterial hypertension).In one study of rosuvastatin, the overall incidence of diabetes was reported: 2.8% in the rosuvastatin group and 2.3% in the placebo group mainly in patients with fasting glucose 5.6-6.9 mmol / l. and glucose-galactose malabsorption, since it contains lactose monohydrate. Effects on the ability to drive vehicles and mechanismsNo research has been conducted on the effect of rosuvastatin on ability to drive vehicles and mechanisms. When driving vehicles and the occupation of potentially hazardous activities, patients should be careful, because dizziness may occur during therapy.