Active substanceRosuvastatinRosuvastatin
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  • Dosage form: & nbsp
    film-coated tablets

    Composition:

    Dosage of 10 mg

    Active substance: rosuvastatin calcium - 10,42 mg, in terms of rosuvastatin - 10,00 mg.

    Excipients (core): corn starch - 73,25 mg, microcrystalline cellulose - 30,00 mg, lactose monohydrate - 52,50 mg, sodium carboxymethyl starch - 3,75 mg, magnesium stearate - 3,00 mg, talc -2,125 mg, croscarmellose sodium - 2, 00 mg, silicon colloidal dioxide 1.50 mg, methyl parahydroxybenzoate 0.175 mg, propyl parahydroxybenzoate 0.035 mg.

    Auxiliary substances (shell): hypersensitivity, 15 cps, 2.919 mg, titanium dioxide 0.852 mg, dibutyl sebacate 0.814 mg, talc 0.768 mg, hypromellose, 5 cp 0.582 mg, silicon colloidal dioxide 0.352 mg.

    Dosage of 20 mg

    Active substance: rosuvastatin calcium - 20,84 mg, calculated as rosuvastatin - 20,00 mg.

    Excipients (core): corn starch - 115,50 mg, microcrystalline cellulose - 55,00 mg, lactose monohydrate - 90,00 mg,sodium carboxymethyl starch 7.50 mg, magnesium stearate 6.00 mg, talc 4.25 mg, croscarmellose sodium 4.00 mg, silicon colloidal dioxide 3.00 mg, methyl parahydroxybenzoate 0.35 mg, propyl parahydroxybenzoate 0 , 07 mg.

    Auxiliary substances (shell): 5,144 mg, titanium dioxide 1,603 mg, dibutyl sebacate 1.395 mg, talc 1.466 mg, hypromellose, 5 cps 0.999 mg, silicon colloidal dioxide 0.603 mg.

    Description:
    Round biconvex, covered with a film coat of white or almost white color tablets; on the cross-section, the core is white or almost white; 10 mg tablets are at risk from one side.

    Pharmacotherapeutic group:lipid-lowering agent - HMG-CoA reductase inhibitor
    ATX: & nbsp

    C.10.A.A   Inhibitors of HMG-CoA reductase

    C.10.A.A.07   Rosuvastatin

    Pharmacodynamics:

    Mechanism of action

    Rosuvastatin is a selective, competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A into mevalonate, the precursor of cholesterol. The main target of the action of rosuvastatin is the liver, where the synthesis of cholesterol (cholesterol) and catabolism of low-density lipoprotein (LDL) is carried out.

    Rosuvastatin increases the number of "liver" LDL receptors on the surface of cells, 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 amount of LDL and VLDL.

    Pharmacodynamics

    Rosuvastatin reduces the elevated concentration of LDL cholesterol (LDL-C), total cholesterol, triglycerides (TG), increases the concentration of high-density cholesterol-lipoprotein (HDL-C), and also reduces the concentration of apolipoprotein B (ApoV), CS-non-HDL, VLDL, T-VLDL and increases the level of apolipoprotein A-I (ApoA-I), reduces the ratio of LDL-C-HDL cholesterol, total cholesterol / cholesterol-HDL cholesterol, and non-HDL / CS-HDL cholesterol and the ApoB / ApoA-1 ratio. Therapeutic effect appears within one week after the beginning of therapy with the drug Rosuvastatin, after 2 weeks of treatment reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved by the 4th week and is maintained with regular intake of the drug.

    Clinical efficacy

    Rosuvastatin is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia; regardlessfrom race, sex or age, incl. in patients with diabetes mellitus and familial hypercholesterolemia.

    In 80% of patients with hypercholesterolemia H and Pb type according to Fredrickson classification

    (the average initial concentration of LDL-C is about 4.8 mmol / L) on the background of taking the drug at a dose of 10 mg, the concentration of LDL-C is less than 3 mmol / l. In patients with heterozygous familial hypercholesterolemia receiving rosuvastatin in a dose of 20-80 mg, there is a positive dynamics of the lipid profile. After titration to a daily dose of 40 mg (12 weeks of therapy), the concentration of LDL-C is reduced by 53%.

    In patients with homozygous familial hypercholesterolemia receiving rosuvastatin in a dose of 20 mg and 40 mg, the average decrease in the concentration of LDL-C is 22%. The additive effect is noted in combination with fenofibrate for the concentration of triglycerides and with nicotinic acid in lipid-lowering doses (more than 1 g / day) for the concentration of HDL-C.

    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 primarily by the liver, which is the main site for the synthesis of cholesterol and the metabolism of LDL-C. The volume distribution of rosuvastatin is approximately 134 liters. Approximately 90% of rosuvastatin binds to blood plasma proteins, mainly albumin.

    Metabolism

    It is subject to limited metabolism (about 10%). Rosuvastatin is a non-core substrate for metabolism by isoenzymes of the cytochrome P450 system. The main isoenzyme involved in the metabolism of rosuvastatin is isoenzyme CYP2C9. Isozymes CYP2C19, CYP3A4 and CYP2D6 are less involved in metabolism.

    The main revealed metabolites of rosuvastatin are N-desmethyl metabolite and lactone metabolites. N-desmethyl is about 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 - by its metabolites.

    Excretion

    About 90% of the dose of rosuvastatin is excreted unchanged through the intestine (including absorbed and not absorbed rosuvastatin). The rest is excreted by the kidneys.The plasma half-life (T1 / 2) is approximately 19 hours. T1 / 2 does not change with increasing dose of the drug. The average geometric plasma clearance is approximately 50 l / h (coefficient of variation 21.7%). As with other inhibitors of HMG-CoA reductase, a membrane cholesterol transporter involved in the hepatic elimination of rosuvastatin plays an important role in the hepatic elimination of rosuvastatin.

    Linearity

    The 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

    Sex and age do not have a clinically significant effect on the pharmacokinetics

    rosuvastatin.

    Ethnic groups

    Pharmacokinetic studies showed approximately a twofold increase in the median AUC (area under the concentration-time curve) and Cmah (the maximum concentration in the blood plasma) of rosuvastatin in patients of Mongoloid nationality (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared to Europeans; Indian patients showed an increase in the median AUC and Cmah 1,3 times.Pharmacokinetic analysis did not reveal clinically significant differences in pharmacokinetics among Europeans and representatives of the Negroid race.

    Renal insufficiency

    In patients with mild to moderate renal failure, the plasma concentration of rosuvastatin or N-sdmetol metabolite does not change significantly. In patients with severe renal insufficiency (creatinine clearance (CK) less than 30 ml / min.), The concentration of rosuvastatin in blood plasma is 3 times higher, and the concentration N-sdmethyl metabolite is 9 times higher than in healthy volunteers. The concentration of rosuvastatin in blood plasma in patients on hemodialysis was approximately 50% higher than in healthy volunteers. Liver failure

    Patients with varying degrees of hepatic insufficiency did not have an increase in T1 / 2 rosuvastatin in patients with a score of 7 or lower on the Child-Pugh scale. In two patients with scores of 8 and 9 on the Child-Pugh scale, there was an increase in T1 / 2 by at least 2-fold. The experience with rosuvastatin in patients with a score above 9 on the Child-Pugh scale is not available.

    Genetic polymorphism

    Inhibitors of HMG-CoA reductase, including rosuvastatin. bind to transport proteins OATP1B1 (a polypeptide transporting organic anions involved in the capture of statins by hepatocytes) BCRP (efflux conveyor). In carriers of genotypes SLCO1B1 (OATP1B1) p.521NC and ABCG2 (BCRP) p.421AA there was an increase in exposure (AUC) to rosuvastatin in 1,6 and 2,4 times, respectively, in comparison with the carriers of genes SLCO1B1 p.521TT and ABCG2 p.421S.

    Indications:
    - Primary hypercholesterolemia according to Fredrickson classification (type Pa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type Hb) as a supplement to the diet, when the diet and other non-pharmacological methods of treatment (for example, physical exercises, weight loss) are insufficient.

    - Family homozygous hypercholesterolemia as a supplement to a diet and other lipid-lowering therapy (eg, LDL-apheresis), or in cases when such therapy is not effective enough.

    - 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 are shown therapy to reduce the concentration of total cholesterol and LDL-C.

    - Primary prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adults without clinical signs of coronary heart disease (CHD), but with an increased risk of its development (age over 50 for men and over 60 for women, increased concentration C-reactive protein (> 2 mg / L) with at least one of additional risk factors, such as hypertension, low concentration of HDL-C, smoking, family history of early onset of coronary artery disease).
    Contraindications:

    For use in a daily dose of 5 mg, 10 mg and 20 mg:

    - increased sensitivity to rosuvastatin or any of the components of the drug;

    - liver diseases in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times the upper limit of the norm);

    - patients with hepatic insufficiency;

    - severe impairment of kidney function (QC less than 30 ml / min.);

    - myopathy;

    - simultaneous administration of cyclosporine;

    - children and adolescents under 18;

    - in women: pregnancy, the period of breastfeeding, the lack of adequate methods of contraception;

    - patients who are predisposed to the development of myotoxic complications;

    - lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the preparation contains lactose).

    For use in a daily dose of 40 mg:

    - increased sensitivity to rosuvastatin or any of the components of the drug;

    - simultaneous administration of cyclosporine;

    - liver diseases in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times the upper limit of the norm);

    - patients with hepatic insufficiency;

    - patients with risk factors for myopathy / rhabdomyolysis, namely:

    - renal failure of moderate severity (CC less than 60 ml / min);

    - hypothyroidism;

    - personal or family anamnesis of muscular diseases;

    - myotoxicity on the background of taking other inhibitors of HMG-CoA reductase or fibrates in the anamnesis;

    - in women: pregnancy, the period of breastfeeding, the lack of adequate methods of contraception;

    - excessive use of alcohol;

    - conditions that may lead to an increase in the plasma concentration of rosuvastatin;

    - simultaneous reception of fibrates;

    - patients of the Mongoloid race;

    - lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the preparation contains lactose).

    Carefully:

    For use in a daily dose of 5 mg, 10 mg and 20 mg:

    Presence of a risk of myopathy / rhabdomyolysis - renal failure, hypothyroidism, personal or family history of hereditary muscle diseases and a previous history of muscle toxicity when using other inhibitors of HMG-CoA reductase or fibrates; excessive use of alcohol; age over 65; conditions in which there was an increase in the plasma concentration of rosuvastatin; race (Mongoloid race); simultaneous appointment with fibrates; liver disease in history; sepsis; arterial hypotension; extensive surgical interventions, trauma, severe metabolic, endocrine or electrolyte disorders, or uncontrolled convulsive seizures.

    For use in a daily dose of 40 mg:

    Renal insufficiency of mild severity (QC more than 60 ml / min); age over 65; liver disease in history; sepsis; arterial hypotension; extensive surgical interventions, trauma, severe metabolic,endocrine or electrolyte disorders, or uncontrolled convulsive seizures.

    Application in pediatric practice

    The effectiveness and safety of the drug in children under 18 years of age is not established. The experience of using the drug in pediatric practice is limited to a small number of children (8 years and older) with family homozygous hypercholesterolemia. Currently, it is not recommended to apply Rosuvastatin in children under 18 years.

    Pregnancy and lactation:
    Rosuvastatin is contraindicated in pregnancy and during breastfeeding. Women of reproductive age should apply adequate methods of contraception against the background of Rosuvastatin treatment.

    Since cholesterol and other cholesterol biosynthesis products are important for fetal development, the potential risk of HMG-CoA reductase inhibition is greater than the benefit of using the drug in pregnant women.

    When diagnosing pregnancy during therapy, taking the drug Rosuvastatin must be terminated immediately.

    Data on the allocation of rosuvastatin to breast milk are not available, therefore, during the period of breastfeeding, the drug should be discontinued.
    Dosing and Administration:

    Inside, do not chew and do not break, swallow whole, washing down with water. The drug can be administered at any time of the day, regardless of the time of meal. Before starting therapy with the drug Rosuvastatin-Vial, the patient should begin to observe the standard hypocholesterolemic diet and continue to observe it during treatment. The dose of the drug should be selected individually depending on the purpose of therapy and the therapeutic response to treatment, taking into account the current recommendations for the target concentration of lipids.

    The recommended initial dose for patients starting to take the drug, or for patients transferred from other HMG-CoA reductase inhibitors, should be 5 or 10 mg of the drug Rosuvastatin-Vial 1 time per day. When choosing the initial dose should be guided by individual cholesterol concentration and take into account the possible risk of cardiovascular complications, as well as assess the potential risk of side effects. If necessary, the dose may be increased to greater after 4 weeks.

    In connection with the possible development of side effects when taking a dose of 40 mg,compared with lower doses of the drug, an increase in the dose to 40 mg after additional doses above the recommended initial dose for 4 weeks of therapy can be performed only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) who did not achieve the desired result of therapy when taking a dose of 20 mg and which will be monitored by a specialist. It is recommended especially careful monitoring of patients receiving the drug in a dose of 40 mg.

    Do not administer a dose of 40 mg to patients who have not previously consulted a doctor. After 2-4 weeks of therapy and / or with an increase in the dose of the drug Rosuvastatin-Vial, control of lipid metabolism parameters is necessary (if necessary, dose adjustment is required).

    Elderly patients

    The initial recommended dose in patients over the age of 70 is 5 mg, otherwise no dosage adjustment is needed depending on age.

    Patients with renal insufficiency

    In patients with mild or moderate renal insufficiency, dose adjustment is not required.Contraindicated the use of all dosages of the drug Rosuvastatin-Vial in patients with severe renal failure (QC less than 30 ml / min.) (See section "Contraindications"). Contraindicated use of the drug at a dosage of 40 mg in patients with moderate impaired renal function (CC less than 60 ml / min.). Patients with moderate renal dysfunction (CC less than 60 mL / min.) Are recommended an initial dose of 5 mg.

    Patients with hepatic insufficiency

    The drug Rosuvastatin-Vial is contraindicated in patients with liver disease in the active phase.

    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. This fact should be taken into account when prescribing the drug Rosuvastatin-Vial to these patient groups. When appointing doses of 10 and 20 mg, the recommended initial dose for patients of the Mongoloid race is 5 mg. Contraindicated appointment of the drug in a dose of 40 mg to patients of the Mongoloid race (see the section "Contraindications").

    Patients who are predisposed to myopathy

    Contraindicated the appointment of the drug in a dose of 40 mg to patients with factors that may indicate a predisposition to the development of myopathy (see section "Contraindications"). When appointing doses of 10 and 20 mg, the recommended initial dose for this group of patients is 5 mg.

    Genetic polymorphism

    In carriers of genotypes SLCO1B1 (OATP1B1) p.521N and ABCG2 (BCRP) p.421AA there was an increase in exposure (AUC) to rosuvastatin in comparison with carriers of genotypes SLCO1B1 P.521TT and ABCG2 C.421SS. For patients carriers of genotypes с.521СС or С.421АА the recommended maximum dose of the drug Rosuvastatin-Vial is 20 mg once a day.

    Concomitant therapy

    Rosuvastatin binds to various transport proteins (in particular, to OATP1B1 and BCRP). With the simultaneous use of the drug Rosuvastatin with medicines (such as ciclosporin, some HIV protease inhibitors, including a combination of ritonavir with atazanavir, lopinavir and / or tipranavir), which increase the concentration of rosuvastatin in blood plasma due to interaction with transport proteins, may increase the risk of myopathy (including rhabdomyolysis).You should read the instructions for the use of these drugs before they are administered concomitantly with the drug Rosuvastatin-Vial. In such cases, the possibility of prescribing alternative therapy or temporary discontinuation should be assessed reception of the drug Rosuvastatin-Vial. If the use of the above drugs is necessary, the ratio of benefit and risk of concomitant therapy with Rosuvastatin-Vial should be assessed and the possibility of reducing its dose should be considered (see "Interactions with Other Drugs").

    Side effects:

    Side effects observed with the use of rosuvastatin, usually expressed slightly and pass independently. As with other inhibitors of HMG-CoA reductase, the incidence of side effects is dose-dependent.

    The frequency of undesirable effects is as follows,

    according to the classification of the World Health Organization:

    Often (> 1/100, <1/10); Infrequently (> 1/1000, <1/100); Rarely (> 1/10 000 <1/1 000); Rarely

    (<1/10 000), including individual reports; Frequency is not set (can not be

    calculated according to available data).

    The immune system

    Rarely: hypersensitivity reactions, including angioedema

    From the endocrine system

    Often: type 2 diabetes mellitus

    From the central nervous system

    Often: headache, dizziness

    From the side of the digestive tract

    Often: constipation, nausea, abdominal pain

    Rarely: pancreatitis

    From the skin

    Infrequent: itching, rash, urticaria

    From the side of the musculoskeletal system

    Often: myalgia

    Rarely: myopathy (including myositis), rhabdomyolysis Other

    Often: asthenic syndrome

    From the side of the urinary system

    In patients who received rosuvastatin, proteinuria can be detected. Changes in the amount of protein in the urine (from absence or trace amounts to ++ or more) are observed in less than 1% of patients receiving 10-20 mg of the drug and about 3% of patients receiving 40 mg of the drug. A slight change in the amount of protein in the urine was noted with a dose of 20 mg. In most cases, proteinuria decreases or disappears during therapy and does not indicate the onset or progression of an existing kidney disease.

    From the side of the musculoskeletal system

    When using rosuvastatin in all dosages 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 or without acute renal insufficiency.

    A dose-related increase in creatine phosphokinase (CK) activity was observed in a small number of patients taking rosuvastatin. In most cases, it was insignificant, asymptomatic and temporary. In case of increased activity of CK (more than 5 times compared with the upper limit of the norm) therapy should be suspended.

    From the side of the liver

    With the use of rosuvastatin, a dose-dependent increase in the activity of "hepatic" transaminases in a small number of patients is observed. In most cases, it is insignificant, asymptomatic and temporary.

    Laboratory indicators

    Increase in the concentration of glucose, bilirubin, activity of gamma-glutamyltranspeptidase, alkaline phosphatase, thyroid dysfunction.

    Postmarketing application

    The following side effects have been reported in the post-marketing application of rosuvastatin:

    On the part of the hematopoiesis system: Frequency not established: thrombocytopenia From the side of the digestive tract Very rarely: jaundice, hepatitis

    Rarely: increased activity of "liver" transaminases Frequency not established: diarrhea

    From the side of the musculoskeletal system

    Very rarely: arthralgia

    Frequency not established: immuno-mediated necrotizing myopathy

    From the central nervous system

    Very rare: loss or loss of memory

    Frequency not established: peripheral neuropathy

    From the respiratory system

    Frequency not established: cough, dyspnea

    From the side of the urinary system

    Very rare: hematuria

    From the skin and subcutaneous fat

    Frequency not established: Stevens-Johnson syndrome

    From the side of the reproductive system

    Very rarely: gynecomastia

    Other

    Frequency not established: peripheral edema

    With the use of some statins, the following side effects have been reported: depression, sleep disturbances, including insomnia and nightmarish dreams, sexual dysfunction, hyperglycemia, increased concentrations of glycosylated hemoglobin.Single cases of interstitial lung disease have been reported, especially with prolonged use of drugs.

    Overdose:
    Symptoms: with the simultaneous administration of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change.

    Treatment: there is no specific treatment for an overdose of rosuvastatin. In case of an overdose, it is recommended to carry out symptomatic treatment and measures aimed at maintaining the functions of vital organs and systems. It is necessary to monitor liver function and the level of CK. It is unlikely that hemodialysis will be effective.
    Interaction:

    Inhibitors of transport proteins

    Rosuvastatin binds to some transport proteins, in particular, to OATP1B1 and BCRP. Concomitant use of drugs that are inhibitors of transport proteins may be accompanied by an increase in the concentration of rosuvastatin in the blood plasma and an increased risk of myopathy.

    Cyclosporine: with simultaneous application of rosuvastatin and cyclosporine AUC rosuvastatin was an average of 7 times higher than that seen in healthy volunteers. Does not affect the plasma concentration of cyclosporine.A drug Rosuvastatin contraindicated in patients receiving ciclosporin (see section "Contraindications").

    Indirect anticoagulants: the initiation of rosuvastatin therapy or an increase in the dose of the drug in patients receiving both vitamin K antagonists (for example, warfarin), can lead to an increase in prothrombin time (International Normalized Relationship - MHO). The cancellation of rosuvastatin or a decrease in the dose of the drug may lead to a decrease MHO. In such cases, control is recommended MHO.

    Gemfibrozil and other lipid-lowering drugs: the combined use of rosuvastatin and gemfibrozil leads to an increase in 2 times the maximum concentration of rosuvastatin in blood plasma and AUC rosuvastatin. Based on the data on the specific interaction, no pharmacokinetically significant interaction with fenofibrate is expected, possibly pharmacodynamic interaction. Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid (more than 1 g / day) increased the risk of myopathy with simultaneous use with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy and when used in monotherapy.If the drug is simultaneously taken with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day), the initial dose of 5 mg is recommended for patients, the dose of 40 mg is contraindicated with simultaneous appointment with fibrates (see section "Contraindications").

    Ezetimibe: simultaneous application of rosuvastatin in a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase AUC rosuvastatin in patients with hypercholesterolemia (see Table 3). It is impossible to exclude an increase in the risk of side effects due to the pharmacodynamic interaction between the drug Rosuvastatin and ezetimibe.

    HIV protease inhibitors (human immunodeficiency virus): despite the fact that the exact mechanism of interaction is unknown, joint intake of HIV protease inhibitors can lead to a significant increase in the exposure of rosuvastatin (see Table 3). The simultaneous administration of rosuvastatin and HIV protease inhibitors in the treatment of patients with HIV is not recommended.

    Antacids: simultaneous application of rosuvastatin and suspensions of antacids containing aluminum and magnesium hydroxide,leads to a decrease in the plasma concentration of rosuvastatin by about 50%. This effect is less pronounced if antacids are administered 2 hours after rosuvastatin administration. The clinical significance of this interaction has not been studied.

    Erythromycin: simultaneous application of rosuvastatin and erythromycin leads to a decrease AUC rosuvastatin by 20% and Cmrosuvastatin rose by 30%. Such interaction can arise as a result of increased intestinal motility caused by the administration of erythromycin.

    Perorach contraceptives / hormone replacement therapy: simultaneous use of rosuvastatin and oral contraceptives increases AUC ethinylestradiol and AUC norgestrel by 26% and 34%, respectively. Such an increase in plasma concentration should be taken into account when choosing a dose of oral contraceptives. Pharmacokinetic data on simultaneous use of the drug Rosuvastatin and hormone replacement therapy are absent, therefore, it is impossible to exclude a similar effect when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.

    Other medicines: no clinically significant interaction between rosuvastatin and digoxin is expected.

    Isozymes of cytochrome P450: research results in vivo and in vitro showed that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. Besides, rosuvastatin is a weak substrate for these isoenzymes. Therefore, interaction of rosuvastatin with other drugs at the metabolic level with the participation of cytochrome P450 isoenzymes is not expected.

    There was no clinically significant interaction between rosuvastatin and fluconazole (inhibitor of isozymes CYP2C9 and CYP3A4) and ketoconazole (inhibitor of isoenzymes CYP2A6 CYP3A4).

    Interaction with medicines. which requires dose adjustment for rosuvastatin (see Table 1)

    Dose of the drug Rosuvastatin should be adjusted if necessary, its simultaneous use with drugs that increase exposure to rosuvastatin. If the exposure is expected to be 2 times or more, the initial dose of the drug Rosuvastatin should be 5 mg 1 time per day.Also, the maximum daily dose of the drug should be adjusted Rosuvastatin so that the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg taken without the simultaneous administration of medications that interact with rosuvastatin. For example, the maximum daily dose of the drug Rosuvastatin at simultaneous application with gemfibrozil is 20 mg (increase in exposure by 1.9 times), with ritonavir / atazanavir - 10 mg (an increase in exposure by 3.1 times).

    Table 1

    The effect of concomitant therapy on exposure to rosuvastatin (AUC, data are listed in descending order)



    Special instructions:

    From the urinary system

    In patients receiving high doses of rosuvastatin (mainly 40 mg), tubular proteinuria was observed, which in most cases was transient. Such proteinuria did not indicate an acute kidney disease or progression of kidney disease. In patients taking the drug at a dose of 40 mg, it is recommended to monitor the performance of kidneys during treatment.

    From the side of the musculoskeletal system

    When rosuvastatin was used in all dosages and, in particular when taking doses of the drug in excess of 20 mg, the following effects on the musculoskeletal system were reported: myalgia, myopathy, in rare cases rhabdomyolysis.

    Determination of the activity of creatine phosphokinase

    Determination of CKK activity should not be performed after intensive physical exertion or in the presence of other possible causes of increased activity of CK, which may lead to incorrect interpretation of the results. If the initial activity of CK is significantly increased (5 times higher than the upper limit of the norm), after 5-7 days, a second measurement should be made. Do not start therapy if a second test confirms the baseline CK activity (more than 5 times higher than the upper limit of the norm). Before the start of therapy

    When using the drug Rosuvastatin, as well as other HMG-CoA reductase inhibitors, caution should be exercised in patients with existing risk factors for myopathy / rhabdomyolysis, the risk-to-benefit ratio of therapy should be considered and clinical observation performed.

    During therapy

    The patient should be informed of the need to report immediately to the doctor about cases of sudden onset of muscle pain, muscle weakness, or spasms, especially in combination with malaise and fever. In such patients, the activity of CK should be determined. Therapy should be discontinued if the activity of CK is significantly increased (more than 5 times as compared to the upper limit of the norm) or if the symptoms from the muscles are pronounced and cause daily discomfort (even if the activity of CK is 5 times lower compared to the upper limit norms). If the symptoms disappear, and the activity of CPA returns to normal, consideration should be given to re-application of the drug Rosuvastatin or other HMG-CoA reductase inhibitors in smaller doses with careful monitoring of the patient. Routine monitoring of the activity of CKK in the absence of symptoms is inappropriate. Very rare cases of immuno-mediated necrotizing myopathy with clinical manifestations in the form of persistent weakness of proximal muscles and increased activity of CKK in the serum during treatment or with stopping of taking statins are noted. rosuvastatin.It may be necessary to conduct additional studies of the muscular system and nervous system, serological studies, as well as therapy with immunosuppressive drugs.

    There were no signs of an increase in the effect on skeletal musculature upon admission rosuvastatin and concomitant therapy. However, an increase in the incidence of myositis and myopathy in patients taking other HMG-CoA reductase inhibitors in combination with fibrin acid derivatives, including gemfibrozil, ciclosporin, nicotinic acid in lipid-lowering doses (more than 1 g / day), azole antifungal agents, HIV protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when combined with certain HMG-CoA reductase inhibitors. Thus, simultaneous use of the drug is not recommended Rosuvastatin and gemfibrozil. It is necessary to carefully weigh the ratio of risk and possible benefit in the joint use of the drug Rosuvastatin and fibrates or lipid-lowering doses of nicotinic acid (more than 1 g / day). Contraindicated drug intake Rosuvastatin in a dose of 40 mg together with fibrates.In 2-4 weeks after the start of treatment and / or with an increase in the dose of the drug Rosuvastatin it is necessary to monitor the lipid metabolism (if necessary, dose adjustment is required).

    Impaired liver function

    It is recommended to carry out the determination of liver function indices before the start of therapy and 3 months after the start of therapy. Reception of the drug Rosuvastatin should stop or reduce the dose of the drug if the activity of "hepatic" transaminases in the serum is 3 times higher than the upper limit of the norm.

    In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, therapy for major illnesses should be performed prior to initiating treatment with the drug Rosuvastatin. Special populations.

    Ethnic groups

    In the course of pharmacokinetic studies among Chinese and Japanese patients an increase in the systemic concentration of rosuvastatin was noted in comparison with the figures obtained among Europeans.

    HIV protease inhibitors

    It is not recommended joint use of the drug with HIV protease inhibitors.

    Lactose

    The drug should not be used in patients with lactose insufficiency,

    intolerance to lactase and glucose-galactose malabsorption.

    Benzoates

    Benzoates, which are part of the drug, may be the cause of allergic reactions (possibly delayed).

    Interstitial lung disease

    When certain statins were used, especially for a long time, single cases of interstitial lung disease were reported. Manifestations of the disease may be shortness of breath, unproductive cough and deterioration, general well-being (weakness, weight loss and fever). If suspicion of interstitial lung disease should be stopped by statin therapy.

    Diabetes mellitus type 2

    In patients with a glucose concentration of 5.6 to 6.9 mmol / L, rosuvastatin therapy was associated with an increased risk of developing type 2 diabetes.

    Effect on the ability to drive transp. cf. and fur:There have been no studies on the effect of rosuvastatin on the ability to drive a vehicle and use mechanisms. Care should be taken when driving vehicles or work associated with increased concentration of attention and psychomotor reaction (dizziness may occur during therapy).
    Form release / dosage:
    The tablets covered with a film membrane, 10 mg, 20 mg.


    Packaging:For 10 tablets in a PVC / aluminum foil blister or 40 or 50 tablets in a high-density polyethylene container with a screw cap made of the same material; 3 blisters or one container, together with instructions for use in a pack of cardboard.
    Storage conditions:Store at a temperature not higher than 25 ° C. Keep out of the reach of children.
    Shelf life:
    3 years.

    Do not use after the expiration date.
    Terms of leave from pharmacies:On prescription
    Registration number:LP-003576
    Date of registration:19.04.2016
    Date of cancellation:2021-04-19
    The owner of the registration certificate:VIAL, LLC VIAL, LLC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp21.05.2016
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