Rosart - instructions for use, analogs, reviews and release forms (5 mg, 10 mg, 20 mg and 40 mg tablets) of the statin drug for lowering cholesterol in adults, children and pregnancy. Composition and alcohol

In this article, you can read the instructions for using the drug Rosart. There are reviews of visitors to the site - consumers of this medication, as well as opinions of physicians specialists on the use of a statin Rosart in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Rosart analogues in the presence of existing structural analogs. Use to reduce cholesterol and prevent cardiovascular diseases in adults, children, as well as during pregnancy and breast-feeding.Composition and interaction of the drug with alcohol.

Rosart - a hypolipidemic drug from the group of statins. A selective competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme that converts HMG-CoA to mevalonate, the precursor of cholesterol.

Increases the number of low-density lipoprotein (LDL) receptors on the surface of hepatocytes, which leads to increased capture and catabolism of LDL, inhibition of the synthesis of very low density lipoproteins (VLDL), reducing the total number of LDL and VLDL. Reduces the high cholesterol-LDL, low-density cholesterol-lipoprotein (LDL), cholesterol-VLDL, total cholesterol, triglycerides (TG), TG-VLDL, apolipoprotein B (ApoV), lowers the ratio of cholesterol-LDL cholesterol, total cholesterol / cholesterol-HDL cholesterol-non-HDL / cholesterol-HDL, Apov / apolipoprotein A-1 (ApoA-1), increases the concentration of cholesterol-HDL, the level of ApoA-1.

The hypolipidemic effect is directly proportional to the magnitude of the prescribed dose. The therapeutic effect appears within 1 week after the initiation of therapy, after 2 weeks reaches 90% of the maximum, reaches a maximum at 4 weeks, and then remains constant.Effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia (regardless of race, gender or age), incl. in patients with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with hypercholesterolemia 2a and 2b type (Fredrickson classification) with an average baseline LDL cholesterol index of about 4.8 mmol / l, the cholesterol-LDL level reaches values ​​below 3 mmol / L when taking the drug at a dose of 10 mg. In patients with homozygous familial hypercholesterolemia, taking the drug at a dose of 20 mg and 40 mg, the average decrease in the level of cholesterol-LDL is 22%.

Additive effect is noted in combination with fenofibrate (in terms of decreasing TG concentration) and with nicotinic acid in lipid-lowering doses of more than 1 g per day (for increasing cholesterol-HDL-C).

Composition

Calcium Rosuvastatin + excipients.

Pharmacokinetics

The systemic exposure of rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily intake. Penetrates through the placental barrier. Rosuvastatin is absorbed mainly by the liver, which is the main site for the synthesis of cholesterol and the metabolism of LDL-C.Binding to plasma proteins (predominantly with albumin) is approximately 90%. Biotransformed in the liver to a small extent (about 10%), being a non-core substrate for cytochrome P450 isoenzymes. As with other HMG-CoA reductase inhibitors, a specific membrane transporter-a polypeptide transporting an organic anion (AATP) 1B1, which plays an important role in its hepatic elimination-is involved in the hepatic capture process. The main isoenzyme involved in the metabolism of rosuvastatin is CYP2C9. Isozymes CYP2C19, CYP3A4 and CYP2D6 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 of inhibiting the circulating HMG-CoA reductase is provided by rosuvastatin, the rest - by its metabolites. About 90% of the dose of rosuvastatin is excreted unchanged through the intestine, the rest - by the kidneys. T1 / 2 - approximately 19 hours, does not change with increasing dose of the drug.The average value of plasma clearance is approximately 50 l / h (coefficient of variation of 21.7%). Sex and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin.

Indications

• primary hypercholesterolemia (type 2a according to Fredrickson classification), including heterozygous hereditary hypercholesterolemia) or mixed (combined) hyperlipidemia (type 2b by Fredrickson), as a supplement to the diet and other non-medicamentous measures (physical activity and weight loss);
• homozygous form of hereditary hypercholesterolemia with insufficient effectiveness of diet therapy and other treatments aimed at reducing lipid concentrations (eg, LDL-apheresis) or if such treatments are not suitable for the patient;
• hypertriglyceridemia (type 4 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 cholesterol;
• prevention of major cardiovascular complications (stroke, heart attack,arterial revascularization) in adults without clinical signs of coronary artery disease, but with an increased risk of developing it (age over 50 for men and over 60 for women, increased concentration of C-reactive protein (more than 2 mg / L) if at least one of additional risk factors, such as hypertension, low concentration of cholesterol-HDL, smoking, family history of early onset of CHD).

Forms of release

Tablets coated with 5 mg, 10 mg, 20 mg and 40 mg.

Instructions for use and dosage

The drug is taken orally, without chewing or chopping, swallowing whole, with water, regardless of time of day and food intake.

Before starting therapy with Rosart, the patient should begin to follow the standard lipid-lowering diet and continue to observe it during treatment.

The dose of the drug should be selected 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 who start taking the drug, or for patients transferred from other HMG-CoA reductase inhibitors, is 5 or 10 mg once daily.When choosing the initial dose should be guided by the concentration of cholesterol in the patient and take into account the risk of cardiovascular complications, as well as the potential risk of adverse reactions. 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, the final titration to a maximum dose of 40 mg should be performed only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia ), who, when taking a dose of 20 mg, did not achieve the target concentration of cholesterol, and which will be under medical supervision.

It is 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, control of lipid metabolism parameters 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 on the Child-Pugh scale below 7, dose adjustment is not required. In patients with values ​​of 8 and 9 on the Child-Pugh scale, a preliminary assessment of renal function should be performed. Experience with rosuvastatin in patients with hepatic insufficiency above 9 points on the Child-Pugh scale is not available. Rosuvastatin is contraindicated in patients with liver disease in the active phase.

With renal failure of mild or moderate severity, dose adjustment is not required. The initial dose of 5 mg is recommended for patients with moderate renal insufficiency (CC less than 60 ml / min). Patients with renal insufficiency of moderate severity (CK less than 30-60 ml / min) administration of the drug in a dose of 40 mg is contraindicated. Taking Rosalt is contraindicated in any dose to patients with severe renal failure (QC 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 in such patients is contraindicated.

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 in a dose of 40 mg in such patients is contraindicated.

Combination Therapy

Rosuvastatin is a substrate for various transport proteins (eg, OATP1B1 and BCRP). Increased risk of myopathy, including rhabdomyolysis, while taking rosuvastatin with medications that increase the concentration of rosuvastatin in blood plasma due to their interaction with transport proteins. This group of substances include cyclosporine, HIV protease inhibitors, including a combination of ritonavir with atazanavir, lopinavir and / or tipranavir. In the event that it may be necessary to decide on the appointment of alternative therapy and, if necessary, temporarily stop taking rosuvastatin. In the case when simultaneous reception can not be avoided,should carefully evaluate the possible risk of interaction and the potential benefits of joint treatment.

Side effect

• thrombocytopenia;
• headache;
• dizziness;
• asthenic syndrome;
• polyneuropathy;
• decreased memory;
• depression;
• peripheral neuropathy;
• sleep disorders, including insomnia and nightmares;
• constipation, diarrhea;
• nausea;
• abdominal pain;
• pancreatitis;
• hepatitis;
• jaundice;
• cough;
• dyspnea;
• interstitial lung disease;
• diabetes;
• myalgia;
• myopathy (including myositis);
• rhabdomyolysis;
• arthralgia;
• itching;
• rash;
• hives;
• hypersensitivity reactions, including angioedema;
• Stevens-Johnson syndrome;
• hematuria (blood in the urine);
• gynecomastia;
• transient increase in AST and ALT activity;
• peripheral edema.

Contraindications

For the preparation Rosart in a daily dose of 5, 10 and 20 mg:

• liver diseases in the active phase, including persistent increase in serum activity of hepatic transaminases (more than 3 times as compared with IGN);
• severe renal dysfunction (KK less than 30 ml / min);
• myopathy;
• simultaneous administration of cyclosporine;
• use in women of reproductive age who do not use adequate methods of contraception;
• pregnancy and the period of breastfeeding;
• age under 18 years (effectiveness and safety not established);
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption (the preparation contains lactose monohydrate);
• increased sensitivity to rosuvastatin or other components of the drug.

For the preparation Rosart in a daily dose of 40 mg:

• liver diseases in the active phase, including persistent increase in serum activity of hepatic transaminases (more than 3 times as compared with IGN);
• myopathy;
• simultaneous administration of cyclosporine;
• use in women of reproductive age who do not use adequate methods of contraception;
• pregnancy and the period of breastfeeding;
• age under 18 years (effectiveness and safety not established);
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption (the preparation contains lactose monohydrate);
• myotoxicity on the background of taking other inhibitors of HMG-CoA reductase or fibrates in anamnesis;
• hypothyroidism;
• renal failure of severe or moderate severity (SC less than 60 ml / min);
• excessive use of alcohol;
• conditions that may lead to an increase in the plasma concentration of rosuvastatin;
• simultaneous reception of fibrates;
• use in patients of the Mongoloid race;
• family or personal history of hereditary muscle diseases;
• increased sensitivity to rosuvastatin or other components of the drug.

Application in pregnancy and lactation

The drug Rosart is contraindicated in pregnancy and lactation.

The use of Rosart in women of reproductive age is possible only if reliable methods of contraception are used and if the patient is informed of the possible risk of treatment for the fetus.

Because cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of inhibiting HMG-CoA reductase exceeds the benefit of using the drug during pregnancy. In the case of diagnosing pregnancy during the treatment with Rosart, the drug should be stopped immediately, and the patients are warned about the potential risk to the fetus.

Data on the allocation of rosuvastatin to breast milk are not available, therefore, when it is necessary to use the drug during lactation, taking into account the possibility of undesirable phenomena in infants, the question of stopping breastfeeding should be addressed.

Use in children

Contraindicated in children and adolescents under the age of 18 years (efficacy and safety not established).

Application in elderly patients

In elderly patients, dose adjustment is not required.

special instructions

Effect on kidney function

In patients who received high doses of rosuvastatin (mainly 40 mg), tubular proteinuria was observed in the urine test strip, which in most cases was transient. Such proteinuria did not indicate an acute kidney disease or progression of kidney disease. The frequency of reports of the development of serious adverse reactions from the kidneys in the postmarketing period was higher in patients taking rosuvastatin at a dose of 40 mg.

When using the drug Rosart at a dose of 40 mg, it is recommended to monitor the indices of kidney function during treatment.

Effect on the musculoskeletal system

With the use of all doses of rosuvastatin and, in particular, when doses exceeding 20 mg were reported, the development of myalgia, myopathy and, in rare cases, rhabdomyolysis. In very rare cases, the development of rhabdomyolysis with simultaneous administration of inhibitors of HMG-CoA reductase and ezetimibe has been reported. In this case, pharmacodynamic interaction can not be ruled out, so caution should be exercised when they are taken together. As with the administration of other inhibitors of HMG-CoA reductase, the frequency of postmarketing observation about the development of rhabdomyolysis associated with rosuvastatin was higher with a dose of 40 mg.

Determination of CKK activity

Determination of the activity of CKK should not be performed after intensive physical exertion or in the presence of other possible causes of an increase in its activity, which may lead to incorrect interpretation of the results. In case the initial activity of CK is significantly increased, after 5-7 days a repeated measurement should be performed - do not start therapy if the repeated test confirms the initial activity of CK (5 times higher than normal).

Before the start of therapy

Caution should be exercised when prescribing Rosart, as well as with the administration of other HMG-CoA reductase inhibitors, to patients with existing risk factors for myopathy / rhabdomyolysis. It is necessary to consider the ratio of expected benefits from therapy and potential risk and to conduct clinical follow-up throughout the course of treatment. In the event that the initial activity of CK is significantly increased (5 times higher than ULN), then do not start treatment with the drug.

During treatment

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 the CK is significantly increased (more than 5 times compared with the IGN) or if the muscular symptoms are pronounced and cause daily discomfort (even if the CKK activity is 5 times less than the VLN). If symptoms disappear and CPK activity returns to normal, re-administration of Rosart or other HMG-CoA reductase inhibitors in smaller doses should be considered with careful monitoring of the patient.Routine monitoring of the activity of CKK in the absence of symptoms is inexpedient.

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 blood serum during treatment or discontinuation of statin use were noted. rosuvastatin.

There were no signs of an increase in the effect on skeletal musculature when taking rosuvastatin and concomitant therapy. However, there have been reports of 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), cyclosporine, nicotinic acid in lipid-lowering doses greater than 1 g per day, azole antifungals, inhibitors protease and macrolide antibiotics. Gemfibrozil increases the risk of myopathy with simultaneous administration with certain HMG-CoA reductase inhibitors, so simultaneous use of gemfibrozil and rosuvastatin is not recommended. We should carefully weigh the ratio of expected benefits and potential risks in the joint use of Rosart and fibrates or nicotinic acid in lipid-lowering doses of more than 1 g per day.

Contraindicated taking RosArt in a dose of 40 mg at the same time as fibrates.

During treatment, especially during the dosage adjustment period of Rosart, every 2-4 weeks the lipid profile should be monitored and, if necessary, the dose of the drug should be changed.

Rosart should not be taken to patients with acute or severe myopathy or risk factors predisposing to the development of renal dysfunction and secondary rhabdomyolysis (eg, sepsis, arterial hypotension, extensive surgery, trauma, severe metabolic disorders, severe endocrine disorders, and severe violations of water-electrolyte balance, uncontrolled convulsions).

Effects on liver function

As with other HMG-CoA reductase inhibitors, rosuvastatin should be used with caution in patients who have abused alcohol and / or have a history of liver disease. 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. Acceptance of the drug Rosart should stop or reduce the dose of the drug if the level of activity of hepatic transaminases in the serum is 3 times higher than VGN.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, the treatment of underlying diseases should be performed prior to treatment with Rosart. In post-marketing surveillance of rosuvastatin, the frequency of reports on the development of serious impairments of liver function (expressed mainly in an increase in hepatic transaminase activity) was higher with a dose of 40 mg.

Ethnic groups

In the course of pharmacokinetic studies among the patients of the Mongoloid race, in comparison with the Caucasoid race, an increase in the systemic concentration of rosuvastatin was noted.

HIV protease inhibitors

In the course of combined administration of rosuvastatin and a combination of different inhibitors of HIV proteases with ritonavir, an increase in the systemic concentration of rosuvastatin is observed. Careful evaluation should be made of a reduction in blood lipid concentrations, and also consider a possible increase in rosuvastatin in 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 for rosuvastatin.

Interstitial lung disease

Some inhibitors of HMG-CoA reductase, especially for a long time, reported single cases of interstitial lung disease. Manifestations of the disease can be shortness of breath, unproductive cough and deterioration in overall health (weakness, weight loss and fever). If suspicion of interstitial lung disease should be discontinued therapy with HMG-CoA reductase inhibitors.

Diabetes mellitus type 2

Some data confirm that HMG-CoA reductase inhibitors increase blood glucose concentration 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 vascular complications, so this fact is not a reason to interrupt the treatment with rosuvastatin. Clinical observation and biochemical blood testing should be performed according to national standards in patients at risk of developing hyperglycemia (blood glucose concentration 5.6-6.9 mmol / L, body mass index over 30 kg / m2, triglyceridemia, hypertension).In one study of rosuvastatin, the overall incidence of diabetes mellitus was reported: 2.8% in the rosuvastatin group and 2.3% in the placebo group, mainly in fasting glucose 5.6-6.9 mmol / l.

Lactose intolerance

The drug Rosart should not be taken to patients with lactose intolerance, lactase deficiency and glucose-galactose malabsorption, since it contains lactose monohydrate.

Impact on the ability to manage vehicles and mechanisms

There have been no studies to study the effect of rosuvastatin on the ability to drive vehicles and mechanisms. When driving vehicles and engaging in potentially hazardous activities, patients should be careful, as dizziness may occur during therapy.

Drug Interactions

Inhibitors of transport proteins

Rosuvastatin is a substrate for some transport proteins, including the membrane transporter OATP1B1 involved in the hepatic capture process, and the transport protein BCRP. The simultaneous administration of rosuvastatin with drugs that inhibit these transport proteins can lead to an increase in the concentration of rosuvastatin in the blood plasma and increase the risk of myopathy.

The simultaneous use of rosuvastatin and cyclosporine does not affect the plasma concentration of cyclosporine, but enhances the effect of rosuvastatin (slowing down its excretion, AUC increases 7-fold, Cmax-11-fold). Simultaneous administration of cyclosporine and rosuvastatin is contraindicated.

Simultaneous reception of Erythromycin and rosuvastatin leads to a decrease in AUC of rosuvastatin by 20% and increases Cmax by 30%. Such interaction can arise as a result of increased intestinal motility caused by the intake of erythromycin.

Patients receiving indirect anticoagulants (eg, warfarin) are recommended to monitor MHO, since initiating or increasing the dose of rosuvastatin may lead to an increase in MHO, and cancellation or reduction of rosuvastatin may lead to a decrease.

Gemfibrozil and other lipid-lowering agents: simultaneous administration of gemfibrozil and rosuvastatin increases Cmax and AUC of rosuvastatin by 2 times. 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 (at least 1 g per day) increased the risk of myopathy with other HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy and when used in quality of monotherapy. With simultaneous administration of rosuvastatin with one of the drugs in this group, patients are advised to take an initial dose of rosuvastatin 5 mg, a daily dose of rosuvastatin 40 mg is contraindicated in this case.

The simultaneous use of rosart and antacids containing aluminum and magnesium hydride leads to a decrease in the plasma concentration of rosuvastatin by approximately 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.

The simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinylestradiol and AUC of norgestrel by 26% and 34%, respectively, which should be taken into account when selecting a dose of oral contraceptives. Pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement therapy are not available, therefore, it is impossible to exclude a similar effect when they are used together.However, a similar combination was widely used during clinical trials of rosuvastatin and was well tolerated by patients.

The results of the studies showed that Rosart 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 such drugs as Fluconazole (inhibitor of isoenzymes CYP2C9 and CYP3A4), Ketoconazole (inhibitor of isoenzymes CYP2A6 and CYP3A4), metabolized by the cytochrome P450 system.

The combined use of 10 mg rosuvastatin and 10 mg ezetimibe in patients with hypercholesterolemia increased the rosuvastatin AUC 1.2-fold. However, the pharmacodynamic interaction between rosuvastatin and ezetimibe can not be excluded with regard to the appearance of undesirable phenomena.

Despite the fact that the exact mechanism of interaction is unknown, the use of HIV protease inhibitors with rosuvastatin can lead to a pronounced increase in the exposure of rosuvastatin. Pharmacokinetic study of simultaneous application of 20 mg rosuvastatin with a combined preparation,containing two inhibitors of HIV proteases (400 mg of lopinavir / 100 mg of ritonavir) in healthy volunteers resulted in approximately a twofold and fivefold increase in rosuvastatin AUC0-24 and Cmax, respectively. Thus, the combined use of rosuvastatin with HIV-protease inhibitors in HIV-infected patients is not recommended.

There was no clinically significant interaction between rosuvastatin and digoxin.

Analogues of the drug Rosart

Structural analogs for the active substance:

• Akorta;
• The Cross;
• Mertenil;
• Rosystark;
• Rosuvastatin;
• Rosewood;
• Rosulip;
• Roxer;
• Tevastor.

Analogues for the pharmacological group (statins):

• Akorta;
• Aktalipid;
• Anistat;
• Apexstatin;
• Atherostat;
• Atokord;
• Atomax;
• Ator;
• Atorvastatin;
• Atorvox;
• Atoris;
• The Vasator;
• Vazilip;
• Zocor;
• Zokor forte;
• Zorstat;
• Cardiostatin;
• The Cross;
• Leskol;
• Leskol Fort;
• Lipobay;
• Lipon;
• Lipostat;
• Lipofford;
• Liprimar;
• Liptonorm;
• Lovacor;
• Lovastatin;
• Lovasterol;
• Mevakor;
• Medostatin;
• Mertenil;
• Ovenkor;
• Pravastatin;
• Rovacor;
• Rosystark;
• Rosuvastatin;
• Rosewood;
• Rosulip;
• Roxer;
• Simva Hexal;
• Simvard;
• Simvakol;
• Simvale;
• Simvastatin;
• Simvastol;
• Symvor;
• Simgal;
• Simlo;
• Sinquard;
• Tevastor;
• Torvazine;
• Torvacard;
• Torvalip;
• Torvas;
• Tulip;
• Holvasim;
• Holletar.

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