Expiration date: 04/2025

Clinico-pharmacological group

(Lipid lowering drug)

Release form, composition and packaging

Tablets, film-coated white color, round, lenticular, with beveled, labeled "5," printed by stamping, on one side, in cross section are visible two layers, the core is white.

Excipients: cellulose microcrystalline - 95.08 mg lactose 40 mg, crospovidon - 7.5 mg; silicon dioxide colloidal - 0.33 mg, magnesium stearate - 1.88 mg.

The composition of the film shell: butylmetacrylate, dimethylaminoethylmethacrylate and methyl methacrylate copolymer (1:2:1) - 1.1 mg, macrogol 6000 - 0.9 mg titanium dioxide 0.5 mg, lactose monohydrate - 2 mg.

10 PCs. - blisters (1) - packs of cardboard.

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

10 PCs. - blisters (3) - packs cardboard.

10 PCs. - blisters (6) - packs cardboard.

10 PCs. - blisters (9) - packs of cardboard.

14 PCs. - blisters (1) - packs of cardboard.

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

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

14 PCs. - blisters (6) - packs cardboard.

Tablets, film-coated white color, round, lenticular, with beveled, labeled "10" applied by stamping, on one side, in cross section are visible two layers, the core is white.

1 tablet contains:

rosuvastatin calcium 5.21 mg,

that corresponds to the content of rosuvastatin 5 mg

Excipients: cellulose microcrystalline - 89.87 mg lactose 40 mg, crospovidon - 7.5 mg; silicon dioxide colloidal - 0.33 mg, magnesium stearate - 1.88 mg.

The composition of the film shell: butylmetacrylate, dimethylaminoethylmethacrylate and methyl methacrylate copolymer (1:2:1) - 1.1 mg, macrogol 6000 - 0.9 mg titanium dioxide 0.5 mg, lactose monohydrate - 2 mg.

10 PCs. - blisters (1) - packs of cardboard.

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

10 PCs. - blisters (3) - packs cardboard.

10 PCs. - blisters (6) - packs cardboard.

10 PCs. - blisters (9) - packs of cardboard.

14 PCs. - blisters (1) - packs of cardboard.

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

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

14 PCs. - blisters (6) - packs cardboard.

Tablets, film-coated white color, round, lenticular, with beveled, labeled "15", caused by stamping, on one side, in cross section are visible two layers, the core is white.

1 tablet contains:

rosuvastatin calcium 10.42 mg,

that corresponds to the content of rosuvastatin 10 mg

Excipients: cellulose microcrystalline - 134.81 mg, lactose 60 mg, crospovidon - 11.25 mg, silica colloidal anhydrous - 0.5 mg, magnesium stearate - 2.82 mg.

The composition of the film shell: butylmetacrylate, dimethylaminoethylmethacrylate and methyl methacrylate copolymer (1:2:1) - 1.65 mg, macrogol 6000 - 1.35 mg, titanium dioxide - 0.75 mg lactose monohydrate - 3 mg.

10 PCs. - blisters (1) - packs of cardboard.

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

10 PCs. - blisters (3) - packs cardboard.

10 PCs. - blisters (6) - packs cardboard.

10 PCs. - blisters (9) - packs of cardboard.

14 PCs. - blisters (1) - packs of cardboard.

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

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

14 PCs. - blisters (6) - packs cardboard.

Tablets, film-coated white color, round, lenticular, with facet, in the cross-section are visible two layers, the core is white.

1 tablet contains:

rosuvastatin calcium 15.62 mg,

that corresponds to the content of the rosuvastatin 15 mg

Excipients: cellulose microcrystalline - 179.75 mg lactose 80 mg, crospovidone 15 mg, silicon dioxide colloidal - 0.66 mg, magnesium stearate - 3.76 mg.

The composition of the film shell: butylmetacrylate, dimethylaminoethylmethacrylate and methyl methacrylate copolymer (1:2:1) - 2.2 mg, macrogol 6000 - 1.8 mg titanium dioxide 1 mg, lactose monohydrate 4 mg.

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

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

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

7 PCs. - blisters (12) - packs of cardboard.

10 PCs. - blisters (1) - packs of cardboard.

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

10 PCs. - blisters (3) - packs cardboard.

10 PCs. - blisters (6) - packs cardboard.

10 PCs. - blisters (9) - packs of cardboard.

Tablets, film-coated white color, capsuleline, lenticular, scored on both sides, in the cross-section are visible two layers, the core is white.

1 tablet contains:

rosuvastatin calcium 20.83 mg,

that corresponds to the content of rosuvastatin 20 mg

Excipients: cellulose microcrystalline - 269.62 mg lactose 120 mg, crospovidon - 22.50 mg, silicon dioxide colloidal - 0.99 mg, magnesium stearate - 5.64 mg.

The composition of the film shell: butylmetacrylate, dimethylaminoethylmethacrylate and methyl methacrylate copolymer (1:2:1) - 3.3 mg, macrogol 6000 - 2.7 mg titanium dioxide 1.5 mg, lactose monohydrate - 6 mg.

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

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

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

7 PCs. - blisters (12) - packs of cardboard.

10 PCs. - blisters (1) - packs of cardboard.

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

10 PCs. - blisters (3) - packs cardboard.

10 PCs. - blisters (6) - packs cardboard.

10 PCs. - blisters (9) - packs of cardboard.

Tablets, film-coated white color, capsuleline, lenticular, cross section are visible two layers, the core is white.

1 tablet contains:

rosuvastatin calcium 31.25 mg,

that corresponds to the content of the rosuvastatin 30 mg

Excipients: cellulose microcrystalline - 359.50 mg lactose 160 mg, crospovidon - 30 mg, silicon dioxide colloidal - 1.32 mg, magnesium stearate - 7.52 mg.

The composition of the film shell: butylmetacrylate, dimethylaminoethylmethacrylate and methyl methacrylate copolymer (1:2:1) - 4.4 mg, macrogol 6000 - 3.6 mg titanium dioxide 2 mg, lactose monohydrate - 8 mg.

Pharmacological action

Hypolipidemic drug. The active ingredient of the drug - rosuvastatin is a selective, competitive inhibitor of HMG-COA reductase, the enzyme that turns 3-hydroxy-3-methylglutarylcoenzyme And mevalonova acid - a precursor of cholesterol. The main target of action of rosuvastatin is the liver, where the synthesis of cholesterol (Cs) catabolism and low density lipoprotein (LDL). Increases the number of hepatic receptors for LDL on the cell surface, increasing the capture and catabolism of LDL, which in turn leads to inhibition of the synthesis of very low density lipoproteins (VLDL), thereby reducing the total number of LDL and VLDL.

Rosuvastatin reduces elevated plasma concentrations of LDL cholesterol (CH-LDL), total Cholesterol, triglycerides (TG), increases the concentration of cholesterol high density lipoproteins (HDL-C). It also reduces the concentration of apolipoprotein b (Apob), HS-elpvp, XC-VLDL, TG-VLDL and increases the concentration of apolipoprotein A-I in plasma. Rosuvastatin reduces the ratio of Cholesterol-LDL/HDL-C, total Cholesterol/HDL-C and HS-elpvp/ HDL-C ratio and Apob/Apoa-1.

The therapeutic effect develops within one week after the start of therapy, after 2 weeks of treatment reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved by 4 weeks of therapy and maintained with continued regular administration of the drug.

Clinical efficacy

Rosuvastatin is effective in adults with hypercholesterolemia with concomitant hypertriglyceridemia, regardless of race, gender or age, including patients with diabetes mellitus or familial hypercholesterolemia.

In 80% of patients with hypercholesterolemia IIA and IIb type according to Fredrickson (middle initial concentration of Cholesterol-LDL, approximately 4.8 mmol/l) in patients receiving rosuvastatin at a dose of 10 mg concentration of XC-LDL reaches values of less than 3 mmol/L.

In patients with homozygous familial hypercholesterolemia rosuvastatin was used in doses of 20-40 mg, the average decrease was 22%.

The additive effect observed in combination with fenofibrate in relation to the content of TG and with nicotinic acid in lipidemias doses in the ratio of the concentration of HDL-C.

Pharmacokinetics

Absorption and distribution

Cmax of rosuvastatin in the blood plasma is reached after approximately 5 h after ingestion. The absolute bioavailability is approximately 20%. It is metabolized primarily by the liver, which is the main organ synthesizing and metabolizing cholesterol cholesterol-LDL. Vd of rosuvastatin is approximately 134 L. Approximately 90% of rosuvastatin is associated with blood plasma proteins, mainly to albumin.

Systemic exposure of rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters are not changed when taken daily.

Metabolism

Undergoes limited metabolism (approximately 10%). Rosuvastatin is a non-specific substrate of cytochrome P450. The main isoenzyme involved in the metabolism of rosuvastatin, is the isoenzyme CYP2C9. The isoenzymes CYP2C19, CYP3A4, CYP2D6 are involved in metabolism to a lesser extent. The main identified metabolites are N-desmethylazelastine and lactonase metabolites.

N-desmethylazelastine about 50% less active than rosuvastatin, lactonase metabolites are pharmacologically inactive. More than 90% of the pharmacological activity for the inhibition of plasma HMG-COA reductase inhibitor rosuvastatin is provided, the rest of its metabolites.

Excretion

About 90% of the rosuvastatin dose is excreted unchanged through the intestines (including the absorbed and unabsorbed rosuvastatin). The remaining part is excreted by the kidneys. T1/2 from plasma is approximately 19 hour (no change with increasing dose). The geometric mean plasma clearance is 50 l/h. 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 "liver" elimination of rosuvastatin.

Pharmacokinetics in special patient groups

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 Morozovskaya in Mongoloids (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with Caucasians, Indians have shown an increase in median AUC and Cmax 1.3 times. Pharmacokinetic analysis revealed no clinically relevant differences in pharmacokinetics among Caucasians and Negroid.

In patients with mild and moderate renal failure, the magnitude of the plasma concentration of rosuvastatin or the N-desmethylazelastine 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-desmethylazelastine 9 times higher than in healthy volunteers. The concentration of rosuvastatin in plasma in patients undergoing hemodialysis, approximately 50% higher than in healthy volunteers.

In patients with chronic alcoholic liver disease, plasma concentrations of rosuvastatin increased moderately. Compared to patients with normal hepatic function patients with hepatic insufficiency (class A according to child-Pugh) the AUC and Cmax of rosuvastatin increased by 60 and 5%, respectively, in patients with hepatic impairment (class b child-Pugh), these figures increased 100% and 21%, respectively. Experience with the use of rosuvastatin in patients with hepatic insufficiency (class C according to child-Pugh (over 9 points)).

Dosage

The drug is taken orally. Tablet do not chew or crush, swallow whole with water, reception is possible at any time of the day regardless of the meal.

Before the start of drug therapy Roxera the patient should follow standard cholesterol-lowering diet and continue to observe her during treatment. The dose should be chosen individually depending on the goals of therapy and therapeutic response to treatment, taking into account national guidelines for target concentrations of lipids in plasma.

The recommended initial dose for patients who start taking the drug or for patients transferred from the reception of other inhibitors of HMG-COA reductase, should be 5 or 10 mg 1 times/day.

While the use of the drug with gemfibrozil, fibrates, nicotinic acid in a dose of 1 g/day patients recommended initial dose of the drug 5 mg. When selecting the starting dose should be guided by the individual concentration of cholesterol in plasma and to take into account the possible risk of cardiovascular complications, you must also consider the potential risk of side effects. If necessary, the dose may be increased after 4 weeks.

In connection with the possible development of side effects at a dose of 40 mg/day compared with lower doses, increase the dose to 40 mg/day after an additional application of doses higher than recommended initial doses for 4 weeks of therapy, 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 therapy at a dose of 20 mg/day, and who will be under the supervision of a physician. Especially advised careful monitoring of patients receiving the drug in a dose of 40 mg/day.

Not recommended dose of 40 mg/day in patients not previously treated by the doctor. After 2-4 weeks of therapy and/or with increasing doses of the drug Roxera necessary control of lipid metabolism (if necessary, dose adjustment is required).

In patients with renal insufficiency mild or moderate severity dose adjustment is not required. In patients with severe renal insufficiency (KK less 30 ml/min) the drug is contraindicated Roxera. The use of the drug in a dose of 30 mg/day to patients with renal insufficiency moderate and severe (KK less 60 ml/min) is contraindicated. Patients with renal insufficiency average degree recommended starting dose is 5 mg/day.

Roxera the drug is contraindicated in patients with liver disease in the active phase. The experience of the drug in patients with hepatic impairment than 9 points (class C) on a scale child-Pugh missing.

Patients over 65 years of age is recommended to start the drug at a dose of 5 mg/day.

Special populations

In the study of pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, the marked increase in systemic concentrations of rosuvastatin among Japanese and Chinese. You should consider this fact when using the drug Roxera these groups of patients. In the application of doses of 10 and 20 mg/day the recommended initial dose for patients of the Mongoloid race is 5 mg/day. Patients of the Mongoloid race, the use of the drug in a dose of 40 mg is contraindicated.

The use of the drug in a dose of 40 mg patients predisposed to the development of myotoxicity complications is contraindicated. If necessary, use doses 10 and 20 mg/day the recommended initial dose for this group of patients is 5 mg.

When applying gemfibrozilom dose Roxera should not exceed 10 mg/day.

Overdose

The clinical picture of overdose not described.

With one taking multiple daily doses of the drug the pharmacokinetic parameters of rosuvastatin are not changed.

Treatment: symptomatic, requires monitoring of liver function and activity of ck, there is no specific antidote, hemodialysis is ineffective.

Drug interactions

Cyclosporine

While the use of rosuvastatin and ciclosporin, rosuvastatin AUC on average 7 times higher than that observed in healthy volunteers. Plasma concentrations of rosuvastatin increased 11 times.

Concurrent use of rosuvastatin does not affect the concentration of cyclosporine in the blood plasma.

Indirect anticoagulants

As in the case of other inhibitors of HMG-COA reductase, the beginning of rosuvastatin therapy or increase in dose in patients concurrently receiving indirect anticoagulants (e.g., warfarin) may lead to an increase in MHO. Cancellation of rosuvastatin or reduction of the dose may lead to a decrease in MHO. In such cases, monitoring of the MHO.

Ezetimib

Concomitant use of rosuvastatin and ezetimibe not accompanied by changes in the AUC or Cmax of both drugs. However, we cannot exclude a pharmacodynamic interaction between rosuvastatin and ezetimibe, manifested by increased risk of developing adverse reactions from the muscles.

Gemfibrozil and other lipid-lowering means

Concomitant use of rosuvastatin and gemfibrozil increases the AUC and Cmax of rosuvastatin by 2 times. Gemfibrozil, fenofibrate, other fibrates and lipidnami doses of nicotinic acid (large doses or the equivalent of 1 g/day) increased the risk of myopathy with concomitant use with inhibitors of HMG-COA reductase (possibly due to the fact that they can cause myopathy and when used in monotherapy).

The simultaneous use of fibrates and of rosuvastatin at a daily dose of 30 mg is contraindicated. In these patients, therapy should begin with a dose of 5 mg/day.

HIV protease inhibitors

The simultaneous use of HIV protease inhibitors can significantly increase plasma concentration of rosuvastatin. Simultaneous application of 20 mg rosuvastatin and a combination of two HIV protease inhibitors (400 mg lopinavir/100 mg ritonavir) accompanied by an increase in the equilibrium AUC(0-24 h) and Cmax of rosuvastatin by 2 and 5 times, respectively.

Antacids

Concomitant use of rosuvastatin and antacids containing aluminium and magnesium hydroxide, leads to a decrease in plasma concentrations of rosuvastatin by about 50%. This effect is expressed weaker, if antacids are applied through 2 h after administration of rosuvastatin.

Erythromycin

Concomitant use of rosuvastatin and erythromycin leads to a decrease in AUC(0-t) of rosuvastatin by 20% and Cmax by 30%. Such interaction may occur as a result of increased intestinal motility caused by the use of erythromycin.

Hormonal contraceptives/hormonal replacement therapy (HRT)

Concomitant use of rosuvastatin and hormonal contraceptives increases the AUC of ethinyl estradiol and norgestrel 26% and 34%, respectively. This increase the concentration in blood plasma should be taken into account when choosing doses of hormonal contraceptives.

Pharmacokinetic data on the simultaneous use of rosuvastatina and hormone replacement therapy do not exist, therefore, we cannot exclude a similar effect with the use of this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.

Digoxin

Clinically significant interactions of rosuvastatin with digoxin is expected.

The cytochrome P450 isoenzymes

Rosuvastatin is neither an inhibitor nor inducer of cytochrome P450. In addition, rosuvastatin is a poor substrate for this isoenzyme system. Clinically significant interaction between rosuvastatin and fluconazole (an inhibitor of isoenzymes CYP2C9 and CYP3A4) and ketoconazole (an inhibitor of CYP2A6 and CYP3A4 isoenzymes) is not marked. Concomitant use of rosuvastatin and Itraconazole (inhibitor of CYP3A4) increases the AUC of rosuvastatin at 28%, which is clinically insignificant. Thus, it is not expected interactions associated with cytochrome P450.

Pregnancy and lactation

Roxera the drug is contraindicated in pregnancy and lactation.

Women of childbearing age should use adequate methods of contraception.

Because cholesterol and cholesterol substances, synthesized from cholesterol important for the development of the fetus, the potential risk of inhibition of HMG-COA reductase to the fetus is greater than the benefit derived from the use of the drug during pregnancy.

In the case of pregnancy during therapy the drug should be immediately discontinued.

Data concerning the allocation of rosuvastatin in breast milk is not available (it is known that other inhibitors of HMG-COA reductase is able to stand out with breast milk), so breast-feeding, the drug should be discontinued.

Side effects

Classification of frequency of side effects: very often (>, 1/10), often (>,1/100, but <,1 10="">,1/1000, but <,1 100="">,1/10 000, but <,1 1000="" 1="" 10="" 000="" p="">,

The frequency of side effects depends on the received dose.

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

CNS: frequently - headache, dizziness, very rarely, polyneuropathy, memory loss.

From the digestive system: often - constipation, nausea, abdominal pain, rarely - pancreatitis, increased liver transaminases; very rarely jaundice, hepatitis, diarrhea.

With the skin: rarely - itching, rash, urticaria, very rare - Stevens-Johnson syndrome.

From the side of musculoskeletal system: often - myalgia, rarely - myopathy (including myositis) and rhabdomyolysis, is very rare - arthralgia. A dose-dependent increase in the activity of CPK is observed in a small number of patients taking rosuvastatin. In most cases it is minor, asymptomatic and transient. In the case of increasing the activity of the KLF more than 5 times the ULN therapy should be suspended.

From the urinary system: often - proteinuria (less than 1% of patients receiving a dose of 10-20 mg/day, and about 3% of patients receiving a dose of 40 mg/day). In most cases, proteinuria decreases or disappears during therapy and does not mean the occurrence of acute or progressive concomitant disease of the kidneys. Very rarely - hematuria.

General disorders: common - asthenia.

Laboratory parameters: increased activity of KFK, the concentration of glucose, bilirubin, activity of GGT, alkaline phosphatase, the change in plasma concentrations of thyroid hormones.

Terms and conditions storage

The drug should be stored out of reach of children at temperature not exceeding 30°C, in original packaging. Shelf life - 2 years.

Testimony

• primary hypercholesterolemia (type IIA according to Fredrickson) or mixed dyslipidemia (type IIb according to Frederickson) as a Supplement to the diet with inefficiency diet and other non-pharmacological treatments (e.g. exercise, weight loss),
  
• family homozygous hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (eg, LDL apheresis) or if such treatment is 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 who have shown therapy to reduce plasma concentrations of Cholesterol and Cholesterol-LDL,
  
• primary prevention of major cardiovascular complications (stroke, myocardial infarction, arterial revascularization) in adults without clinical signs of CHD, but with an increased risk of its development (age older than 50 years for men and over 60 for women, increased plasma concentration of C-reactive protein (?2 g/l) in the presence of at least one of additional risk factors such as hypertension, low plasma concentration of HDL-C, Smoking, early onset coronary artery disease in family anamnesis).
  

Contraindications

At a daily dose to 30 mg

• liver disease in active phase (including the persistent increase of transaminases and improvement in liver transaminases in the serum of more than 3 times compared with CAH),
  
• severe renal insufficiency (KK less 30 ml/min),
  
• myopathy,
  
• concomitant use of cyclosporine,
  
• patients predisposed to the development myotoxicity complications
  
• pregnancy,
  
• breastfeeding,
  
• use in women of childbearing age not using adequate contraceptive methods
  
• lactose intolerance, lactase deficiency, syndrome of glucose-galactose malabsorption,
  
• the age 18 years,
  
• hypersensitivity to rosuvastatin or any component of the drug.
  

At a daily dose of 30 mg or more

• liver disease in active phase (including the persistent increase of transaminases and improvement in liver transaminases in the serum of more than 3 times compared with CAH),
  
• renal insufficiency moderate and severe (KK less 60 ml/min),
  
• myopathy,
  
• concurrent use of cyclosporine,
  
• patients predisposed to the development myotoxicity complications
  
• pregnancy,
  
• breastfeeding,
  
• use in women of childbearing age not using adequate contraceptive methods
  
• hypothyroidism,
  
• muscle disease in history (incl. family),
  
• myotoxicity the use of other inhibitors of HMG-COA reductase inhibitors or fibrates,a history of
  
• excessive use of alcohol,
  
• status that can lead to increase the concentration of rosuvastatin in plasma,
  
• concomitant use of fibrates,
  
• lactose intolerance, lactase deficiency, syndrome of glucose-galactose malabsorption,
  
• patients of the Mongoloid race,
  
• the age 18 years,
  
• hypersensitivity to rosuvastatin or any component of the drug.
  

With caution

At a daily dose to 30 mg

• the risk of myopathy/rhabdomyolysis - renal failure, hypothyroidism, hereditary muscle disease in history (incl. family) and previous history of muscle toxicity with the use of other inhibitors of HMG-COA reductase inhibitors or fibrates,
  
• excessive use of alcohol,
  
• over 65 years of age,
  
• a condition in which increased plasma concentrations of rosuvastatin,
  
• race (Mongoloid race, Japanese and Chinese),
  
• concomitant use of fibrates,
  
• diseases of liver in anamnesis,
  
• sepsis
  
• hypotension,
  
• extensive surgical interventions, injuries, severe metabolic, endocrine or electrolyte disorders or uncontrolled seizures,
  
• simultaneous application with ezetimibe.
  

At a daily dose of 30 mg or more

• renal failure mild (QC than 60 ml/min),
  
• over 65 years of age,
  
• diseases of liver in anamnesis,
  
• sepsis
  
• hypotension,
  
• extensive surgical interventions, injuries, severe metabolic, endocrine or electrolyte disorders or uncontrolled seizures,
  
• simultaneous application with ezetimibe.
  

Special instructions

Violation of kidney function

Patients receiving high doses of rosuvastatin (particularly 40 mg/day) was observed tubular proteinuria, which was detected with test strips and in most cases were recurrent or transient. So proteinuria is not a sign of acute or progression of associated kidney disease. The frequency of serious renal dysfunction, observed in post-marketing study of rosuvastatin, higher when taking doses of 40 mg/day. In patients receiving the drug Roxera dose 30 or 40 mg/day, is recommended to monitor indicators of kidney function during treatment (not less than 1 time in 3 months).

Effect on musculoskeletal system

When using rosuvastatin all doses, but particularly at doses exceeding 20 mg/day, was reported the following effects on the musculoskeletal system: myalgia, myopathy, and in rare cases rhabdomyolysis. Observed very rare cases of rhabdomyolysis with concomitant administration of inhibitors of HMG-COA reductase and ezetimibe. This combination should be used with caution, because it is impossible to exclude pharmacodynamic interaction.

As in the case of other inhibitors of HMG-COA reductase, the frequency of rhabdomyolysis in post-marketing use of the drug Roxera higher when the dose of 40 mg/day.

Determination of activity of KFK

The activity of KFK is impossible to determine after intense exercise and when other possible reasons for the increase in its activity, it can lead to misinterpretation of the results. In the case that the initial activity of KFK significantly exceeded (5 times the ULN), after 5-7 days, you should retest it. You cannot start treatment if the results of the reanalysis confirmed the initial high activity of KFK (more than 5-fold excess CAH).

Before therapy

Depending on a daily dose of the drug Roxera should be administered with caution to patients with existing risk factors for myopathy/rhabdomyolysis, or the drug is contraindicated. These factors include:

• impaired renal function,
  
• hypothyroidism,
  
• muscle disease in history (incl. family),
  
• myotoxicity effects while taking other inhibitors of HMG-COA reductase inhibitors or fibrates,a history of
  
• excessive use of alcohol,
  
• over 65 years of age,
  
• a condition in which can increase the concentration of rosuvastatin in plasma,
  
• concomitant use of fibrates.
  

These patients should assess the risk and possible benefits of therapy. It is also recommended to conduct clinical monitoring. If the initial activity of KFK is more than 5 times compared with CAH, the treatment with the drug Roxera cannot be started.

During the period of drug therapy

Should inform the patient about the need for an immediate message to the doctor in case of sudden occurrence of muscle pain, muscle weakness or spasms, 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 symptoms from muscles are pronounced and cause daily discomfort (even if ck activity is not more than 5 times the ULN). If the symptoms disappear and the activity of CPK returns to normal, you should consider the resumption of the drug Roxera or other inhibitors of HMG-COA reductase in smaller doses, under close medical supervision. Monitor the activity of CPK in the absence of symptoms is inappropriate.

Signs of increasing effects on skeletal muscles when taking rosuvastatin and concomitant therapy were observed. However, 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 (e.g., gemfibrozil), cyclosporine, nicotinic acid lepidotrigla doses (more 1 g/day), antifungal agents - derivatives Azola, HIV protease inhibitors and macrolide antibiotics.

While the use of some inhibitors of HMG-COA reductase inhibitor gemfibrozil increases risk of myopathy. Thus, the simultaneous use of the drug Roxera and gemfibrozil is not recommended (in doses less than 30 mg/day). The benefits of further changes in the plasma concentration of lipids in the combined use of the drug Roxera with fibrates or nicotinic acid in lipidemias doses should be carefully weighed, taking into account possible risk. Rosuvastatin at a dose of 30 mg/day or more is contraindicated for combination therapy with fibrates.

In connection with the increased risk of rhabdomyolysis drug Roxera should not be applied to patients with acute conditions, which can lead to myopathy or predisposing to the development of renal failure (eg, sepsis, hypotension, extensive surgical interventions, injuries, severe metabolic, endocrine and electrolyte disorders or uncontrolled seizures).

Liver

Depending on a daily dose of the drug Roxera should care be exercised in patients with excessive alcohol consumption and/or with a history of liver disease or its use is contraindicated.

Recommended determination in liver function tests before therapy and 3 months after it started. The use of the drug Roxera should stop or reduce the dose of the drug, if the activity of liver transaminases in the blood serum in 3 times the VGN.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, before treatment with the drug Roxera should be the therapy of major diseases.

Ethnic features

During pharmacokinetic studies in Mongoloids compared to Caucasians was an increase in plasma concentrations of rosuvastatin.

Roxera the drug contains lactose, therefore it should not be used in patients with lactose intolerance, lactase deficiency, a syndrome of glucose-galactose malabsorption.

Effects on ability to drive vehicles and management mechanisms

Studies on the influence of the drug Roxera on the ability to drive vehicles and operate machinery was not carried out. However, given the possibility of developing dizziness and other side effects, it is necessary to exercise caution when driving and other mechanisms that require high concentration and psychomotor speed reactions

Use in impaired renal function

In patients with renal insufficiency mild or moderate severity dose adjustment is not required. In patients with severe renal insufficiency (KK less 30 ml/min) the drug is contraindicated Roxera. The use of the drug in a dose of 30 mg/day to patients with renal insufficiency moderate and severe (KK less 60 ml/min) is contraindicated. Patients with renal insufficiency average degree recommended starting dose is 5 mg/day.

Use in hepatic impairment

Roxera the drug is contraindicated in patients with liver disease in the active phase. The experience of the drug in patients with hepatic impairment than 9 points (class C) on a scale child-Pugh missing.