Rosulip 20mg coated film pills N28
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Active ingredients
Rosuvastatin
Release form
Pills
Composition
Rosuvastatin zinc 21.36 mg,; which corresponds to the content of rosuvastatin 20 mg; Excipients: ludipress - 260.64 mg (lactose monohydrate (93%), povidone (3.5%), crospovidone (3.5%)), crospovidone - 15 mg, magnesium stearate - 3 mg.; The composition of the shell: opadry II white 85F18422 - 7.5 mg (polyvinyl alcohol (40%), titanium dioxide (25%), macrogol 3350 (20.2%), talc (14.8%)).
Pharmacological effect
Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase - an enzyme that catalyzes the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, which is a precursor of cholesterol (Xc). Rosuvastatin increases the number of LDL receptors on the surface of liver cells, thereby enhancing the absorption and catabolism of LDL, and also suppresses the synthesis of VLDLP in the liver. As a result, the total amount of VLDL and LDL particles is reduced.; It lowers the elevated concentration of low-density lipoprotein cholesterol (LDL), total cholesterol and triglycerides, and also increases the concentration of high-density lipoprotein cholesterol (LDL). In addition, rosuvastatin reduces the concentration of apolipoprotein B (ApoB), non-HDL cholesterol (Xc-non-LPVP), very low-density lipoprotein cholesterol (Xc-VLDL), very low-density lipoprotein triglycerides (TG-VLDL), and increases the content of apolipoprotein-low-density lipoprotein (TG-VLVP) and increases the content of apolipoprotein-very low density lipoprotein (TG-VLDL) and increases the content of apolipoprotein, low density lipoprotein, and low-density lipoprotein cholesterol and increases the content of apolipoprotein and low-density lipoprotein cholesterol; ). Rosuvastatin also reduces the ratio of Xc-LDL / Xc-HDL, total cholesterol / Xc-HDL, Xc-non-LPVP / Xc-HDL and ApoV / ApoA-I; The therapeutic effect of the drug occurs within one week after starting treatment. After 2 weeks of therapy, the effectiveness reaches a level that is 90% of the maximum possible. The maximum therapeutic effect is usually achieved by the 4th week of therapy and is maintained with regular use. The safety and efficacy of rosuvastatin in the pediatric population has not been proven. For this category of patients, the experience of using the drug is limited to a small number of patients (aged 8 years and older) with homozygous hereditary hypercholesterolemia.
Pharmacokinetics
Absorption; Cmax of rosuvastatin in the blood plasma is reached approximately 5 hours after ingestion. The absolute bioavailability of the drug is about 20%. Distribution; Rosuvastatin is intensively absorbed by the liver, where the main synthesis of cholesterol and the elimination of Xc-LDL occurs.Vd of rosuvastatin reaches 134 l.; Approximately 90% of rosuvastatin binds to plasma proteins, mainly albumin.; Metabolism; Rosuvastatin undergoes limited metabolism (about 10%) in the liver. It is a non-core substrate for cytochrome P450 isoenzymes. CYP2C9 is the main isoenzyme involved in rosuvastatin metabolism. CYP2C19, CYP3A4 and CYP2D6 isoenzymes are less involved in metabolism. The main metabolites identified for 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 its metabolites; Excretion; Approximately 90% of the dose of rosuvastatin is excreted unchanged through the intestine. T1 / 2 of the drug from blood plasma is approximately 19 hours and does not change with increasing dose of the drug. Rosuvastatin plasma clearance reaches an average of 50 l / h (coefficient of variation - 21.7%) .; As in the case of other HMG-CoA reductase inhibitors, a membrane cholesterol carrier is involved in the process of hepatic seizure of rosuvastatin.; It plays an important role in the hepatic elimination of rosuvastatin .; The systemic bioavailability of rosuvastatin increases in proportion to the dose. When using the drug several times a day, the pharmacokinetic parameters do not change. Pharmacokinetics in special groups of patients; Gender and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin. (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with Caucasians; Indian patients showed an increase in the median AUC and Cmax by a factor of 1.3. The analysis did not reveal clinically significant differences in pharmacokinetics among Caucasians and Negroids. In patients with mild to moderate renal insufficiency, the plasma concentration of rosuvastatin or N-desmethyl does not change significantly. In patients with severe renal failure (CC less than 30 ml / min), plasma concentration of rosuvastatin is 3 times higher, and N-desmethyl concentration is 9 times higher than in healthy volunteers.The plasma concentration of rosuvastatin in hemodialysis patients was about 50% higher than in healthy volunteers. In patients with various stages of liver failure, there was no increase in Rosuvastatin T1 / 2 (patients with a score of 7 or lower on the scale Drink). In 2 patients with grades 8 and 9 on the Child-Pugh scale, an increase in T1 / 2 was noted at least 2 times. Experience with rosuvastatin in patients with a score above 9 on the Child-Pugh scale is absent.
Indications
- primary hypercholesterolemia (type IIa according to Fredrickson) or mixed hypercholesterolemia (type IIb according to Fredrickson) as a supplement to the diet when diet and other non-drug therapies (eg exercise, weight loss) are insufficient; - Homozygous hereditary hypercholesterolemia as a supplement to the diet and other methods of treatment aimed at reducing the concentration of lipids in the blood (for example, LDL apheresis), as well as in cases when these methods are not sufficiently effective; - hypertriglyceridemia (type IV according to Fredrickson) as a supplement to the diet; - to slow the progression of atherosclerosis as a supplement to the diet in patients, including those who show therapy to reduce the level of total Hc and LDL-C; - prevention of major cardiovascular complications (stroke, myocardial infarction, 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 concentration of C-reactive protein (≥2 mg / l) in the presence of at least one of the additional risk factors such as hypertension, low concentrations of HD-C, HDL, smoking, a family history of an early onset of CHD).
Contraindications
For pills of 10 mg and 20 mg; - 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 as compared with VGN); - severe renal dysfunction (CC less than 30 ml / min); - myopathy; - simultaneous administration of cyclosporine; - pregnancy; - lactation period; - lack of adequate methods of contraception in women with intact reproductive function; - predisposition to the development of myotoxic complications; - children's and teenage age up to 18 years (due to the lack of sufficient clinical data, efficacy and safety have not been established); - lactose intolerance,lactase deficiency or glucose-galactose malabsorption (the drug contains lactose); - hypersensitivity to rosuvastatin and other components of the drug.; For 40 mg pills; - 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 compared to VGH), experience use of the drug in patients with a score above 9 on the Child-Pugh scale is absent; - simultaneous administration of cyclosporine; - the presence of risk factors for the development of myopathy / rhabdomyolysis: moderate renal failure (CC less than 60 ml / min), hypothyroidism, an indication in the personal or family history of the presence of muscular diseases, myotoxicity while taking other HMG-CoA reductase inhibitors or fibrates in anamnesis, excessive alcohol consumption, conditions that can lead to an increase in the plasma concentration of rosuvastatin, concomitant use of fibrates, patients of the Mongoloid race; - pregnancy; - lactation period; - lack of adequate methods of contraception in women with intact reproductive function; - children's and teenage age up to 18 years (due to the lack of sufficient clinical data, efficacy and safety have not been established); - lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the product contains lactose); - Hypersensitivity to rosuvastatin and other components of the drug. With caution should use the drug in the form of pills 10 mg and 20 mg if there is a risk of myopathy / rhabdomyolysis - renal failure, hypothyroidism, an indication in personal or family history of the presence of hereditary muscular diseases, an indication a history of muscle toxicity with the use of other HMG-CoA reductase inhibitors or fibrates; with excessive use of alcohol; in patients over the age of 65; conditions in which there is an increase in the plasma concentration of rosuvastatin; in patients of the Mongoloid race; simultaneously with fibrates; with a history of liver diseases; sepsis; hypotension; extensive surgical interventions, injuries; in severe metabolic, endocrine or electrolyte disturbances or uncontrolled convulsive seizures.; With caution, use the drug in the form40 mg pills in patients with mild renal insufficiency (CC more than 60 ml / min); over the age of 65; with a history of liver diseases; sepsis; hypotension; extensive surgical interventions, injuries, severe metabolic, endocrine or electrolyte disorders or uncontrolled seizures.
Use during pregnancy and lactation
Rosulip is contraindicated in pregnancy and lactation (breastfeeding). When diagnosing pregnancy during therapy, use of the drug should be stopped immediately.; Women of reproductive age should use adequate methods of contraception. Since Xc and its biosynthesis products are important for fetal development, the potential risk of inhibition of HMG-CoA reductase exceeds the benefits of the drug. about the allocation of rosuvastatin with breast milk are absent, therefore, if necessary, use of the drug during lactation, breastfeeding should be stopped.
Dosage and administration
The drug is taken orally. The tablet should be swallowed whole, washed down with water, not chewed or crushed. Rosulip can be taken at any time of the day, regardless of the meal. Before the treatment with Rosulip is started, the patient should be given a standard diet low in cholesterol. The patient must follow a diet during the entire course of therapy. The dose of the drug should be selected individually depending on the indications and therapeutic response to treatment, taking into account current recommendations on target lipid levels. Recommended initial dose of Rosulip for patients starting the drug or for patients transferred from other HMG-CoA inhibitors - reductase, is 5 or 10 mg 1 time / day. When choosing the initial dose, one should be guided by the patient’s cholesterol content and take into account the risk of cardiovascular complications, and the potential risk of side effects should be assessed. If necessary, after 4 weeks the dose may be increased.; After applying for 4 weeks a dose exceeding the recommended initial dose,its subsequent increase to 40 mg can be performed only in patients with severe hypercholesterolemia and with a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) who have not achieved the desired result of therapy at a dose of 20 mg and who will be under the supervision of a specialist. Particularly careful monitoring of patients receiving the drug at a dose of 40 mg is recommended. For the treatment of patients over 65, the recommended starting dose is 5 mg. There is no need for other changes in the dose of the drug related to the age of the patients. Mild or moderate severity of dose adjustment is not required for patients with renal insufficiency. Patients with moderate renal impairment (CC less than 60 ml / min) are recommended an initial dose of 5 mg. A dose of 40 mg is contraindicated in patients with moderate renal impairment. In case of severe renal insufficiency, Rosulip is contraindicated in any doses. When prescribing the drug in doses of 10 mg and 20 mg, the recommended starting dose for patients of Mongoloid race is 5 mg. The purpose of the drug in a dose of 40 mg is contraindicated in patients of the Mongoloid race. When prescribing the drug in doses of 10 mg and 20 mg, the recommended initial dose for patients predisposed to myopathy is 5 mg. 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. After 2-4 weeks of therapy and / or increasing the dose of Rosulip, control of lipid metabolism indices is necessary, and dose adjustment is necessary if necessary.
Side effects
During therapy with rosuvastatin, predominantly mild and transient adverse reactions were recorded. As with other HMG-CoA reductase inhibitors, the incidence of adverse reactions associated with rosuvastatin therapy is dose dependent.; Classification of adverse reactions versus incidence: often (from> 1/100 to less than 1/10), rarely (from> 1/1000 to less than 1/100), rarely (from> 1/10 000 to less than 1/1000), very rarely (less than 1/10 000), the frequency is unknown (it is impossible to determine based on the available data) .; On the part of the immune system: rarely - hypersensitivity reactions, including angioedema; s nervous system: often - headache, dizziness; very seldom - polyneuropathy, loss or loss of memory.; From the digestive system: often - constipation, nausea,abdominal pain; infrequently, a slight, asymptomatic, transient increase in liver transaminase activity; rarely - pancreatitis; very rarely - jaundice, hepatitis; frequency is unknown - diarrhea. From the skin and subcutaneous structures: infrequently - pruritus, rash and urticaria; frequency is unknown - Stevens-Johnson syndrome. From the musculoskeletal system: often - myalgia; rarely, myopathy (including myositis) and rhabdomyolysis with or without acute renal failure; frequency unknown - immune necrotizing myopathy. A dose-dependent increase in CPK concentration was observed in a small number of patients taking rosuvastatin. In most cases, it was minor, asymptomatic and temporary. In the case of increasing the concentration of CK more than 5 times higher than VGN therapy should be suspended. Very rarely - arthralgia. From the urinary system: proteinuria (less than 1% of patients receiving a dose of 10-20 mg and about 3% of patients receiving a dose of 40 mg). In most cases, proteinuria diminishes or disappears during therapy and does not mean the onset or the progression of an existing kidney disease. Very rarely - hematuria.; On the part of the respiratory system: the frequency is unknown - cough, shortness of breath.; On the part of laboratory parameters: rarely - thrombocytopenia; frequency unknown - hyperglycemia, increased concentrations of glycated hemoglobin, bilirubin, GGT activity, ALP.; Other: often - asthenic syndrome; very rarely - gynecomastia; frequency unknown - possible thyroid dysfunction.; The following adverse events were reported during the treatment with some statins: frequency unknown - sleep disturbances, including insomnia and nightmares, depression; sexual dysfunction, isolated cases of interstitial lung disease (especially with prolonged use).
Overdose
Treatment: there is no specific antidote. It is recommended to carry out symptomatic treatment and measures aimed at maintaining the functions of vital organs and systems. Monitoring of liver function and serum CK level is necessary. The effectiveness of hemodialysis is unlikely.
Interaction with other drugs
Cyclosporine: with simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was on average 7 times higher than that observed in healthy volunteers. Simultaneous use leads to an increase in plasma concentration of rosuvastatin 11 times, the plasma concentration of cyclosporine does not change.; Vitamin K antagonists: starting therapy with rosuvastatin or increasing the dose of the drug in patients receiving vitamin K antagonists (for example, warfarin) may result to an increase in prothrombin time and MHO. Canceling rosuvastatin or reducing its dose may lead to a decrease in MHO. In such cases, it is recommended to control MHO.; Gemfibrozil and lipid-lowering drugs: the combined use of rosuvastatin and gemfibrozil leads to a 2-fold increase in Cmax in plasma and AUC of rosuvastatin. Perhaps pharmacodynamic interaction. Gemfibrozil, other fibrates and nicotinic acid in lipid-lowering doses (more than 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 as monotherapy. At the same time taking the drug with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day), an initial dose of 5 mg is recommended for patients. Therapy with rosuvastatin 40 mg is contraindicated with the concomitant use of fibrates.; Ezetimibe: the simultaneous use of Rosulip and ezetimib is not accompanied by changes in the AUC and Cmax of both drugs. However, pharmacodynamic interaction with the development of side effects cannot be ruled out between rosuvastatin and ezetimibe.; HIV protease inhibitors: although the exact mechanism of interaction is unknown, co-administration of HIV protease inhibitors can lead to a significant increase in the exposure of rosuvastatin. A pharmacokinetic study on the simultaneous use of 20 mg of rosuvastatin with a combination preparation containing two protease inhibitors (400 mg of lopinavir / 100 mg of ritonavir) in healthy volunteers resulted in approximately a twofold and fivefold increase in AUC (0-24) and Cmax of rosuvastatin, respectively.Therefore, simultaneous administration of rosuvastatin and protease inhibitors in the treatment of patients with HIV is not recommended. Antacids: the simultaneous use of rosuvastatin and suspensions of antacids containing aluminum and magnesium hydroxide reduces the plasma concentration of rosuvastatin by about 50%. This effect is less pronounced if the antacid suspension is applied 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.; Erythromycin: the simultaneous use of rosuvastatin and erythromycin leads to a 20% decrease in AUC of rosuvastatin and a 30% increase in Rosuvastatin CUC, probably due to increased intestinal motility caused by taking erythromycin; Oral contraceptives / hormone replacement therapy (erythromycin); ): simultaneous use of rosuvastatin and oral contraceptives increases AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively. Such an increase in plasma concentration should be taken into account when selecting the dose of oral contraceptives against the background of Rosulip. Pharmacokinetic data on the simultaneous use of Rosulip and HRT are absent, therefore, a similar effect cannot be excluded when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.; Other drugs: no clinically significant interaction of rosuvastatin with digoxin is expected.; Cytochrome P450 isozymes: in vivo and in vitro results showed that rosuvastatin is not an inhibitor, nor inducer of isoenzymes of the cytochrome P450 system. In addition, rosuvastatin is a weak substrate for these isoenzymes. There was no clinically significant interaction between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of CYP2A6 and CYP3A4 isoenzymes). The combined use of rosuvastatin and itraconazole (an inhibitor of the isoenzyme CYP3A4) increases the AUC of rosuvastatin by 28% (clinically insignificant). Thus, interactions associated with the cytochrome P450 system are not expected.
special instructions
When using the drug Rosulip in a dose of 40 mg, it is recommended to monitor indicators of renal function.; When using the drug Rosulip in all doses,especially more than 20 mg, it has been reported about the development of myalgia, myopathy and in rare cases - rhabdomyolysis. The determination of CPK activity should not be carried out after intense physical exertion or if there are other possible reasons for the increase in CPK activity, which can lead to a misinterpretation of the results. If the initial activity of CPK is significantly increased (5 times higher than VGN), then in 5-7 days it is necessary to re-measure. You should not start therapy if the repeated test confirms increased activity of CPK (5 times higher than VGN) .; When prescribing Rosulip (as well as other HMG-CoA reductase inhibitors) in patients with existing risk factors for rhabdomyolysis, it is necessary to consider the ratio of expected benefits and potential risk and clinical observation.; It is necessary to inform the patient of the need to immediately report to the doctor about cases of unexpected muscle pain, muscle weakness or spasms, especially in combination with edomoganiem 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 compared to VGN) or if the muscular symptoms are pronounced and cause daily discomfort (even if the activity of KFK is 5 times less than VGN). If symptoms disappear and CK activity returns to normal, consideration should be given to reappointment of Rosulip 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. There are no signs of an increase in toxic effects on skeletal muscles when using Rosulip as part of a combination therapy. An increase in the incidence of myositis and myopathy was reported in patients taking other HMG-CoA reductase inhibitors in combination with fibric acid derivatives (including gemfibrozil), cyclosporine, nicotinic acid in lipid-lowering doses (more than 1 g / day), azole antifungal agents, inhibitors proteases and macrolide antibiotics. Gemfibrozil increases the risk of myopathy, while the appointment with some HMG-CoA reductase inhibitors.Thus, simultaneous administration of Rosulip and gemfibrozil is not recommended. It is necessary to carefully weigh the ratio of the expected benefit and potential risk in the joint use of Rosulip and fibrates or nicotinic acid in lipid-lowering doses (more than 1 g / day); 2-4 weeks after starting treatment and / or increasing the dose of Rosulip, monitoring of indicators is necessary lipid metabolism (dose adjustment required if necessary); It is recommended to determine the activity of transaminases before initiating therapy and 3 months after initiating therapy. Taking Rosulip should stop or reduce the dose of the drug if the serum transaminase activity is 3 times higher than VGN.; In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of the main diseases should be carried out before starting treatment with Rosulip. drug in patients with impaired liver function, corresponding to more than 9 points on the Child-Pugh scale, are absent.; Very rare cases of interstitial lung disease have been registered valis in patients treated with certain drugs of the statin group. As a rule, these cases were observed with long-term statin therapy. Interstitial lung disease is manifested by shortness of breath, an unproductive cough and deterioration of the general condition (fatigue, weight loss and fever). If interstitial lung disease is suspected, statin therapy should be discontinued. Pharmacokinetic studies indicate that Rosuvastatin has a higher bioavailability in patients of the Mongoloid race than those of the Caucasians. galactose malabsorption, because the drug contains lactose.; Use in Pediatrics; The efficacy and safety of using the drug in children and adolescents under the age of 18 years has not been established. The experience of using the drug in pediatric practice is limited to a small number of children (8 years and older) with familial homozygous hypercholesterolemia. Currently, it is not recommended to use Rosulip in children.; Influence on the ability to drive vehicles and control mechanisms; Patients should be careful when driving vehicles or working that require increased concentration of attention and speed of psychomotor reaction, becausedizziness may occur during therapy.