Expiration date: 11/2026

Clinico-pharmacological group

(Lipid lowering drug)

Release form, composition and packaging

Tablets, film-coated white or almost white, round, lenticular, with engraving "E" on one side and the number "591" on the other, without or almost without smell.

Excipients: ludipress - 65.16 mg (lactose monohydrate - 93%, povidone - 3.5%, crospovidon - 3.5%), crospovidone - 3.75 mg, magnesium stearate - 0.75 mg.

The composition of the shell: Opadry II white 85F18422 - 1.9 mg (polyvinyl alcohol - 40%, titanium dioxide 25%, macrogol 3350 - 20.2%, talc - 14.8%).

7 PCs. - blisters (2) - packs of cardboard.

7 PCs. - blisters (4) - packs of cardboard.

7 PCs. - blisters (8) - packs of cardboard.

Tablets, film-coated white or almost white, round, lenticular, with engraving "E" on one side and the number "592" on the other, without or almost without smell.

1 tablet contains:

rosuvastatin zinc 5.34 mg,

that corresponds to the content of rosuvastatin 5 mg

Excipients: ludipress - 130.32 mg (lactose monohydrate - 93%, povidone - 3.5%, crospovidon - 3.5%), crospovidone - 7.5 mg, magnesium stearate - 1.5 mg.

The composition of the shell: Opadry II white 85F18422 - 3.8 mg (polyvinyl alcohol - 40%, titanium dioxide 25%, macrogol 3350 - 20.2%, talc - 14.8%).

7 PCs. - blisters (2) - packs of cardboard.

7 PCs. - blisters (4) - packs of cardboard.

7 PCs. - blisters (8) - packs of cardboard.

Tablets, film-coated white or almost white, round, lenticular, with engraving "E" and the number "593" on one side, without or almost without smell.

1 tablet contains:

rosuvastatin zinc 10.68 mg,

that corresponds to the content of rosuvastatin 10 mg

Excipients: ludipress - 260.64 mg (lactose monohydrate - 93%, povidone - 3.5%, crospovidon - 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%).

7 PCs. - blisters (2) - packs of cardboard.

7 PCs. - blisters (4) - packs of cardboard.

7 PCs. - blisters (8) - packs of cardboard.

Tablets, film-coated white or almost white, oval, biconvex, engraved with "E" and the number "594" on one side, without or almost without smell.

1 tablet contains:

rosuvastatin zinc 21.36 mg,

that corresponds to the content of rosuvastatin 20 mg

Excipients: ludipress - 521.28 mg (lactose monohydrate - 93%, povidone - 3.5%, crospovidon - 3.5%), crospovidone - 30 mg, magnesium stearate - 6 mg.

The composition of the shell: Opadry II white 85F18422 - 15 mg (polyvinyl alcohol - 40%, titanium dioxide 25%, macrogol 3350 - 20.2%, talc - 14.8%).

7 PCs. - blisters (2) - packs of cardboard.

7 PCs. - blisters (4) - packs of cardboard.

7 PCs. - blisters (8) - packs of cardboard.

Pharmacological action

Rosuvastatin is a selective and competitive inhibitor of HMG-COA reductase, the enzyme catalyzing the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, which is a precursor of cholesterol (CH). Rosuvastatin increases the number of LDL receptors on the surface of liver cells, thereby increases the uptake and catabolism of LDL and inhibiting the synthesis of VLDL in the liver. This reduces the total number of particles of VLDL and LDL.

Reduces the increased concentration of cholesterol low-density lipoprotein (TC-LDL), total cholesterol and triglycerides, and also increases the concentration of cholesterol high density lipoproteins (HDL-C). In addition, rosuvastatin reduces the concentration of apolipoprotein b (Apob), cholesterol delpup (XC-nelup), cholesterol very low density lipoproteins (XC-VLDL), triglycerides of very low density lipoproteins (TG-VLDL) and increases the amount of apolipoprotein A-I (Apoa-I).

Rosuvastatin also reduces the ratio of Cholesterol-LDL/HDL-C, total cholesterol/HDL-C, HS-elpvp/HDL-C and Apob/Apoa-I.

The therapeutic effect of the drug occurs within one week after the start of treatment. 2 weeks of therapy effectiveness achieves a level that is 90% of the maximum possible. The maximum therapeutic effect is usually achieved by 4 weeks of therapy and maintained with regular admission.

The safety and efficacy of rosuvastatin in pediatric populations has not been proven. For this category of patients experience with the drug is limited to a small number of patients (aged 8 years and older) with homozygous hereditary hypercholesterolemia.

Pharmacokinetics

Suction

Cmax of rosuvastatin in the blood plasma is reached after approximately 5 h after ingestion. The absolute bioavailability of the drug is about 20%.

Distribution

Rosuvastatin intensively absorbed by the liver, where it is the main cholesterol synthesis and excretion of Cholesterol-LDL. Vd reaches 134 L. rosuvastatin

Approximately 90% of rosuvastatin is associated with blood plasma proteins, mainly to albumin.

Metabolism

Rosuvastatin undergoes limited metabolism (approximately 10%) in the liver. Is a non-core substrate for isoenzymes of cytochrome P450. The main isoenzyme involved in the metabolism of rosuvastatin, a is CYP2C9. The isoenzymes CYP2C19, CYP3A4 and CYP2D6 involved in the metabolism to a lesser extent. The main identified metabolites of rosuvastatin are N-desmethyl and lactonase metabolites. N-desmethyl about 50% less active than rosuvastatin, lactonase metabolites are pharmacologically inactive. More than 90% of the pharmacological activity for the inhibition of circulating HMG-COA reductase inhibitor rosuvastatin is provided, the rest of its metabolites.

Excretion

Approximately 90% of the rosuvastatin dose is excreted unchanged through the intestines.

Approximately 5% of the dose appears kidneys in an unmodified form. T1/2 of the drug from plasma is approximately 19 hours and does not change with increasing doses of the drug. Plasma clearance of rosuvastatin reaches an average of 50 l/h (coefficient of variation 21.7%).

As in the case of other inhibitors of HMG-COA reductase in the process of "liver" capture of rosuvastatin involved membrane Transporter of cholesterol and performs 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 pharmacokinetic parameters are not changed.

Pharmacokinetics in special clinical cases

Gender and age do not have a clinically meaningful effect on the pharmacokinetics of rosuvastatin.

Pharmacokinetic studies showed approximately a twofold increase in median AUC and Cmax of rosuvastatin in plasma in patients of Asian ethnicity (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with representatives of the European race, in Indian patients shows the increase in median AUC and Cmax 1.3 times. The analysis did not reveal clinically important differences in pharmacokinetics among Caucasians and blacks.

In patients with mild and moderate renal failure, the magnitude of the plasma concentration of rosuvastatin or the N-desmethyl does not change significantly. In patients with severe renal insufficiency (KK less 30 ml/min), the concentration of rosuvastatin in plasma is 3 times higher, and the concentration of N-desmethyl 9 times higher than in healthy volunteers. The concentration of rosuvastatin in plasma of patients on hemodialysis were approximately 50 % higher than in healthy volunteers.

In patients with different stages of hepatic insufficiency is not revealed increasing T1/2 of rosuvastatin (patients with score 7 and below on a scale child-Pugh). 2 patients with scores of 8 and 9 on a scale child-Pugh noted an increase in T1/2, at least 2 times. Experience with the use of rosuvastatin in patients with a score above 9 on a scale child-Pugh missing.

Dosage

Inside, do not chew or crush the tablet, swallow whole with water. The drug Rosolie can be taken any time of the day, regardless of meals. Before you start treatment with Rosalie, the patient must assign a standard diet low in cholesterol. The patient needs to follow a diet throughout the course of therapy. The dose should be selected individually depending on indications and therapeutic response to treatment, taking into account the current recommendations for target levels of lipids.

The recommended initial dose of the drug Rosolie for patients who start taking the drug or for patients transferred from the reception of other inhibitors of HMG-COA reductase is 5 or 10 mg 1 times/day. When selecting the starting dose should be guided by the content of cholesterol in a patient and to take into account the risk of developing cardiovascular complications, and to assess the potential risk of side effects. If necessary after 4 weeks, the dose may be increased.

After intake for 4 weeks of doses in excess of recommended starting, then increase to 40 mg can be carried out only in patients with severe hypercholesterolemia and high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) who have not achieved the desired result of the therapy when taken in a dose of 20 mg and who will be under the supervision of a specialist. Especially advised careful monitoring of patients receiving the drug in a dose of 40 mg.

For patients over 65 years of age the recommended starting dose of 5 mg. the Need for other changes in the drug dose related to age of the patients was missing.

Patients with renal insufficiency mild or moderate severity dose adjustment is not required. Patients with moderate impaired renal function (KK less 60 ml/min) the recommended initial dose of the drug 5 mg. Dose of 40 mg is contraindicated in patients umerennye with impaired renal function. In renal failure, severe drug Rosolie is contraindicated at any dose.

When assigning doses of 10 mg and 20 mg the recommended starting dose for patients of Asian race is 5 mg. Contraindicated use of the drug at a dose of 40 mg to patients of Asian race.

When assigning doses of 10 mg and 20 mg the recommended starting dose for patients predisposed to myopathy, Achatina recommended dose is 5 mg. Contraindicated use of the drug at a dose of 40 mg patients with factors that may indicate a predisposition to the development of myopathy.

After 2-4 weeks of therapy and/or with increasing doses of the drug Rosolie necessary control of lipid metabolism, if necessary, dose adjustment is required.

Overdose

Treatment: no specific antidote. Recommended symptomatic treatment and measures aimed at maintaining the functions of vital organs and systems. Requires monitoring of liver function and CPK level in the blood serum. The effectiveness of hemodialysis is unlikely.

Drug interactions

Ciclosporin: during concomitant use of rosuvastatin and cyclosporine AUC of rosuvastatin was on average 7 times higher than the value which was observed in healthy volunteers. Joint application increases the concentration of rosuvastatin in plasma at 11 times the plasma concentration of cyclosporine is not changed.

Vitamin K antagonists: the beginning of rosuvastatin therapy or increase in dosage in patients receiving both vitamin K antagonists (e.g. warfarin) may cause an increase in prothrombin time and MHO. Cancellation of rosuvastatin or reduction of the dose may lead to a decrease in MHO. In such cases, control MHO.

Gemfibrozil and lipid-lowering means: the combined use of rosuvastatin and gemfibrozil leads to an increase of 2 times the Cmax in plasma and AUC of rosuvastatin. Possible pharmacodynamic interaction. Gemfibrozil, other fibrates and nicotinic acid in lipidemias doses (more 1 g/day) increased the risk of myopathy during concomitant use with other inhibitors of HMG-COA reductase, possibly due to the fact that they can cause myopathy and when used as monotherapy. While taking the drug with gemfibrozil, fibrates, nicotinic acid in lipidemias doses (more 1 g/day) patients recommended initial dose of the drug 5 mg. rosuvastatin Therapy in dose of 40 mg is contraindicated with concomitant use of fibrates.

Ezetimib: simultaneous use of the drug Rosalie and ezetimibe was not accompanied by a change in AUC and Cmax of both drugs. However, between rosuvastatin and ezetimibe we cannot exclude a pharmacodynamic interaction with the development of side effects.

Inhibitors of HIV protease: despite the fact that the exact mechanism of interaction is unknown, the co-administration of inhibitors of the HIV protease can result in a significant increased exposure of rosuvastatin. Pharmacokinetic study on the simultaneous application of 20 mg rosuvastatin with combination drug containing two protease inhibitors (400 mg lopinavir/100 mg ritonavir) in healthy volunteers resulted in approximately twofold and fivefold increase in AUC(0-24) and Cmax of rosuvastatin, respectively. Therefore it is not recommended concomitant use of rosuvastatin and protease inhibitors in the treatment of patients with HIV

Antacids: concurrent use of rosuvastatin and suspensions of antacids containing aluminum and magnesium hydroxide, leads to a decrease in plasma concentrations of rosuvastatin by about 50%. This effect is expressed weaker, if antacids suspension is applied through 2 h after administration of rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin: concomitant use of rosuvastatin and erythromycin reduces the rosuvastatin AUC by 20% and Morozovskaya 30%, probably due to increased intestinal motility caused by erythromycin reception.

Oral contraceptives/hormone replacement therapy (HRT):concomitant use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol was norgestrel and AUC of 26% and 34%, respectively. This increase in the plasma concentration should be taken into account in the selection of dose oral contraceptives on the background of the application Rosalia. Pharmacokinetic data on the simultaneous use of Rosolia of HRT do not exist and, therefore, we cannot exclude a similar effect when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.

Other drugs: not expected to be clinically significant interactions of rosuvastatin with digoxin.

The cytochrome P450 isoenzymes: the results of studies in vivo and in vitro showed that rosuvastatin is neither an inhibitor or inducer of isozymes of cytochrome P450. In addition, rosuvastatin is a poor substrate for these isoenzymes. Was not observed clinically significant interactions between rosuvastatin and fluconazole (an inhibitor of isoenzymes CYP2C9 and CYP3A4) and ketoconazole (an inhibitor of isoenzymes CYP2A6 and CYP3A4). The combined use of rosuvastatin and Itraconazole (inhibitor of CYP3A4) increases the AUC of rosuvastatin by 28% (clinically insignificant). Thus, it is not expected interactions associated with cytochrome P450.

Pregnancy and lactation

Rosalie contraindicated during pregnancy and lactation (breastfeeding). When the diagnosis of pregnancy in the course of therapy, the drug should be discontinued immediately.

Women of childbearing age should use adequate methods of contraception.

As Cholesterol and products of its biosynthesis are important for the development of the fetus, the potential risk of inhibition of HMG-COA reductase is greater than the benefit derived from the use of the drug.

Data on the allocation of rosuvastatin in breast milk is not available, so if you need the use of the drug during lactation breastfeeding should be discontinued.

Side effects

Against the background of rosuvastatin therapy were recorded mainly light and transient adverse events. Similar to other inhibitors of HMG-COA reductase, the frequency of adverse reactions associated with treatment with rosuvastatin, characterized by dose-dependency.

Classification of adverse reactions according to frequency of occurrence: often (?1/100 to <,1 10="" 1="" 1000="" 100="" 000="" p="">,

The immune system: rarely - hypersensitivity reactions, including angioedema.

From the nervous system: often - headache, dizziness, very rarely, polyneuropathy, memory loss.

From the digestive system: often - constipation, nausea, abdominal pain, infrequently, minor asymptomatic transient elevation of transaminases, rarely pancreatitis; very rarely jaundice, hepatitis, unspecified frequency - diarrhea.

The skin and subcutaneous structures: infrequently - itching, rash, and urticaria, unspecified frequency - Stevens-Johnson syndrome.

From the side of musculoskeletal system: often - myalgia, rarely - myopathy (including myositis) and rhabdomyolysis with acute renal failure. A dose-dependent increase in the concentration of CPK is observed in a small number of patients taking rosuvastatin. In most cases it was insignificant, asymptomatic and transient. In the case of increasing the concentration of CPK, more than 5 times the ULN therapy should be suspended. Very rare - 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 decreases or disappears during therapy and does not mean the occurrence of acute or progression of existing renal diseases. Very rarely - hematuria.

The respiratory system: frequency unknown cough, shortness of breath.

From the laboratory parameters: increase in the concentration of glucose, bilirubin, activity of GGT, alkaline phosphatase.

Other: often - asthenic syndrome, the possible dysfunction of the thyroid gland.

The following adverse events were reported during therapy with some statins: sleep disturbances, including insomnia and nightmares, sexual dysfunction, depression, very rare cases of interstitial lung diseases, which were mainly recorded in long-term therapy with statins.

Terms and conditions storage

The drug should be stored out of reach of children at temperature not exceeding 30°C. shelf Life - 2 years.

Testimony

• primary hypercholesterolemia (type IIA according to Fredrickson, including family heterozygous hypercholesterolemia) hypercholesterolemia or mixed (type IIb according to Frederickson) as an adjunct to diet when diet and other non-pharmacological treatments (e.g. exercise, weight reduction) are inadequate,
  
• homozygous familial hypercholesterolemia as an adjunct to diet and other therapies aimed at reducing the level of lipids in blood (e.g. LDL apheresis), as well as in cases where these methods are not effective
  
•  hypertriglyceridemia (type IV according to Fredrickson) as a Supplement to the diet,
  
• to slow the progression of atherosclerosis as an adjunct to diet in patients, including which therapy is shown to reduce total Cholesterol and Cholesterol-LDL.
  

Contraindications

For tablets of 10 mg and 20 mg

• liver disease in the active phase, including a persistent increase in serum transaminases and any increase in transaminaz in the serum (more than 3 times compared with CAH),
  
• severe violations of kidney function (KK less 30 ml/min),
  
• myopathy,
  
• concomitant use of cyclosporine,
  
• pregnancy, lactation, and lack of adequate methods of contraception in women with preserved reproductive function,
  
• predisposition to developing myotoxicity complications
  
• children up to age 18 years (due to lack of sufficient clinical data the efficacy and safety of not installed),
  
• lactose intolerance, lactase deficiency or glucose-galactose malabsorption (product contains lactose),
  
• hypersensitivity to rosuvastatin and other drug ingredients.
  

For tablets 40 mg

• liver disease in the active phase, including a persistent increase in serum transaminases and any increase in transaminaz in the serum (more than 3 times compared with CAH), experience of the drug in patients with a score above 9 on the scale of child-Pugh missing,
  
• concomitant use of cyclosporine,
  
• the presence of risk factors for myopathy/rhabdomyolysis: kidney failure of moderate severity (KK less 60 ml/min),
  
• hypothyroidism,
  
• personal or family history of muscle disease,
  
• myotoxicity on a background of reception of other inhibitors of HMG-COA reductase inhibitors or fibrates,a history of
  
• excessive use of alcohol,
  
• States that may lead to increased plasma concentrations of rosuvastatin,
  
• concurrent administration of fibrates,
  
• patients of Asian race,
  
• pregnancy, lactation, and lack of adequate methods of contraception to women with intact reproductive function
  
• children up to age 18 years (due to lack of sufficient clinical data the efficacy and safety of not installed),
  
• lactose intolerance, lactase deficiency or glucose-galactose malabsorption (product contains lactose),
  
• hypersensitivity to rosuvastatin and other drug ingredients.
  

With caution the drug should be used in the form of tablets of 10 mg and 20 mg at the risk of myopathy/rhabdomyolysis - renal impairment, hypothyroidism, personal or family history of hereditary muscular diseases and previous history of muscle toxicity with the use of other inhibitors of HMG-COA reductase inhibitors or fibrates, and excessive use of alcohol in patients older than 65 years, the States, in which increased plasma concentrations of rosuvastatin in patients of Asian race, along with fibrates, liver diseases in history, sepsis, arterial hypotension, extensive surgical interventions, injuries, severe metabolic, endocrine or electrolyte disorders or uncontrolled seizures.

With caution the drug should be used in the form of tablets 40 mg in patients with renal insufficiency, mild (QC than 60 ml/min), aged over 65 years, with liver diseases in history, sepsis, arterial hypotension, extensive surgical interventions, injuries, severe metabolic, endocrine or electrolyte disorders or uncontrolled seizures.

Special instructions

In applying the drug Rosalie at a dose of 40 mg is recommended to monitor indicators of kidney function.

In applying the drug Rosolie in all doses, especially more than 20 mg, reported on the development of myalgia, myopathy and rarely rhabdomyolysis.

Determination of activity of KFK should not be after intense exercise or if there are other possible reasons for the increased activity of KFK, which may lead to misinterpretation of the results. If the initial activity of CPK is significantly elevated (5 times ULN), 5-7 days should be measured again. You should not start the therapy if the second test confirms the increased activity of CPK (in 5 times above ULN).

In appointing the drug Rosalie (as well as other inhibitors of HMG-COA reductase inhibitor) in patients with existing risk factors for rhabdomyolysis it is necessary to consider the ratio of expected benefits and potential risks and conduct clinical observation.

Should inform the patient about the need for an immediate message to the doctor about the cases of sudden occurrence of muscle pain, muscle weakness or cramps, especially in combination with malaise and fever. These patients should determine the activity of KFK. Therapy should be discontinued if the CPK activity increased significantly (more than 5 times compared with CAH), or if muscle symptoms are pronounced and cause daily discomfort (even if ck activity less than 5 times compared with CAH). If the symptoms disappear, and the activity of CPK returns to normal, you should consider re-appointment Rosalia or other inhibitors of HMG-COA reductase in smaller doses with careful monitoring of the patient. Routine monitoring of CPK activity in the absence of symptoms is inappropriate. There were no signs of increased toxic effects on skeletal muscles when using the drug Rosolie in a combination therapy. There is a reported increase in the incidence of myositis and myopathy in patients taking other inhibitors of HMG-COA reductase inhibitor in combination with fibroevoy acid derivatives (including gemfibrozil), cyclosporine, nicotinic acid lepidotrigla doses (more 1 g/day), azole antifungals, inhibitors eroteis and macrolide antibiotics. Gemfibrozil increases risk of myopathy with concomitant administration with certain inhibitors of HMG-COA reductase. Thus, not recommended simultaneous with the appointment of the drug Rosalie and gemfibrozil. You should carefully weigh the ratio of expected benefits and potential risks in a joint application of the drug Rosalie and fibrates or nicotinic acid in lipidemias doses (more 1 g/day).

2-4 weeks after the start of treatment or when increasing the dose Rosolie necessary control of lipid metabolism (if necessary, dose adjustment is required).

It is recommended to determine the activity of transaminases before therapy and 3 months after initiation of therapy. The drug Rosolie should stop or reduce the dose if transaminases activity in blood serum in 3 times the VGN. In patients with hypercholesterolemia due to hypothyroidism or nefroticski syndrome therapy major diseases should be carried out before the start of drug treatment Rosalie. Clinical experience and data on the use of the drug in patients with impaired liver function, corresponding to more than 9 points on a scale child-Pugh, no. Very rare cases of interstitial lung disease were recorded in patients receiving some drugs from the group of statins. As a rule, these cases were observed during long-term therapy with statins. Interstitial lung disease manifested by shortness of breath, non-productive cough and deterioration in General condition (fatigue, weight loss and fever). If there is suspected interstitial lung disease, statin therapy should be discontinued.

The results of pharmacokinetic studies indicate that patients of Asian race the bioavailability of rosuvastatin is higher than that of Europeans.

This drug should not be taken by patients with lactose intolerance, lactase deficiency or glucose-galactose malabsorption, because the drug contains lactose.

Use in Pediatrics

The efficacy and safety of the drug in children under 18 years not installed. The experience of the drug in pediatric practice limited to a small number of children (8 years and older) family homozygous hypercholesterolemia. Currently not recommended for use in children Rosalie.

Effects on ability to drive vehicles and management mechanisms

Patients should observe caution while driving vehicles or work requiring high concentration and psychomotor speed reactions, because during treatment may occur dizziness.