Redistatin 10 mg tablet number 30

Author Ольга Кияница

2017-05-11

Amount in a package 30
Product form Pills
Manufacturer -
Registration certificate UA/14948/01/02
The main medicament -
morion code 392635

Redistatin (REDISTATIN) instructions for use

Composition

active ingredient: rosuvastatin; 1 coated tablet contains rosuvastatin calcium equivalent to rosuvastatin 5 mg or 10 mg or 20 mg or 40 mg

Excipients:

tablets of 5 mg: cellulose microcrystalline lactose monohydrate, crospovidone; meglumine; magnesium stearate Opadry II Yellow 32 K520046 (titanium dioxide (E 171), quinoline yellow (E 104), red charming AC (E 129), indigo (E 132));

tablets of 10 mg, 20 mg and 40 mg: cellulose microcrystalline lactose monohydrate, crospovidone; meglumine;magnesium stearate Opadry II Pink 32 K540017 (titanium dioxide (E 171), red charming AC (E 129), indigo (E 132), yellow sunset FCF (E 110)).

Dosage form

Film-coated tablets.

Basic physical and chemical properties:

5 mg tablets : pills from light yellow to yellow, round, film-coated, with "5" on one side and "company logo" on the other side;

tablets of 10 mg biconvex tablets from light pink to pink, round, film-coated, with "10" on one side and "company logo" on the other side;

tablets of 20 mg biconvex tablets from light pink to pink, round, film-coated, with "20" on one side and "company logo symbol" on the other side;

tablets of 40 mg biconvex tablets from light pink to pink, oval, film-coated, with a "40" on one side and a "company logo symbol" on the other side.

Pharmacological group

Lipid-lowering drugs. Inhibitors of HMG-CoA reductase. ATX code. C10A A07.

Pharmacological properties

Pharmacodynamics.

Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A into mevalonate, the precursor of cholesterol. The primary site of rosuvastatin is the liver - the target organ for lowering cholesterol.

Rosuvastatin increases the number of hepatic low-density lipoprotein (LDL) receptors on the cell surface, 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. Rosuvastatin reduces the increased amount of LDL cholesterol (LDL-C), total cholesterol, triglycerides and increases the amount of high-density lipoprotein (HDL-C) cholesterol. It also reduces the amount of apolipoprotein B (ApoB), high-density non-lipoprotein cholesterol (XC-non-HDL), cholesterol-VLDL, very low density lipoprotein triglycerides (TG-VLDL) and increases the level of apolipoprotein A-I (ApoA-I).Rosuvastatin also reduces the ratio of LDL cholesterol / HDL cholesterol, total cholesterol and HDL-C, low-density non-lipoprotein cholesteryl (CS-non-LDLP) / HDL-C and the Apov / ApoA-I ratio.

The therapeutic effect is achieved within 1 week after the start of therapy, and after 2 weeks of treatment the effect reaches 90% of the maximum possible. The maximum effect, as a rule, is achieved after 4 weeks and after that is permanently preserved.

Pharmacokinetics.

Suction.

After taking the maximum concentration of rosuvastatin in the blood plasma is reached at 5:00. Absolute bioavailability is about 20%.

Distribution.

Rosuvastatin accumulates in the liver, which is the site of primary cholesterol synthesis and clearance of LDL cholesterol. The volume distribution of rosuvastatin is approximately 134 liters. Approximately 90% of rosuvastatin binds to plasma proteins, mainly albumin.

Metabolism.

Rosuvastatin experiences limited biological transformation (about 10%). Investigation of the metabolic transformation and in vitro using human hepatocytes suggests that rosuvastatin is a non-core substrate for cytochrome P450 isoenzymes. The main isoenzyme involved in the metabolic conversion of rosuvastatin is the CYP2C9 enzyme, whereas the 2C19, 3A4 and 2D6 isoenzymes are less involved in the process. The main revealed metabolites of rosuvastatin are N-dysmethyl and lactone metabolites. Metabolite N-dimethyl is about 50% less active than rosuvastatin, and lactone metabolites are considered clinically inactive. Rosuvastatin provides an inhibition of more than 90% of the circulating HMG-CoA reductase.

Conclusion.

About 90% of the dose of rosuvastatin is excreted unchanged with feces (in the form of absorbed and unadsorbed active substance), the rest is excreted in the urine. Approximately 5% is excreted unchanged in the urine. The half-life of the plasma is approximately 19 hours. The duration of the half-life does not change with increasing dose. The geometric mean of the plasma clearance is approximately 50 l / h (coefficient of variation 21.7%). As in the case of other HMG-CoA reductase inhibitors, the membrane transporter OATP-C is involved in the process of getting rosuvastatin in the liver. This transporter plays an important role in the hepatic elimination of rosuvastatin.

Linearity.

The indicators of the systemic effect of rosuvastatin increase in proportion to the dose. With repeated daily administration of the drug, no change in pharmacokinetic parameters occurs.

Special populations of patients.

Age and sex.

Clinically significant effect of age and sex of patients on the pharmacokinetic parameters of rosuvastatin was not found.

Ethnic groups.

Comparative data of pharmacokinetic studies indicate an increase of about 2-fold in the values of AUC and C max when taking the drug by patients of Asian descent (Japanese, Chinese, Filipino, Vietnamese and Korean) compared with patients of the Caucasoid race; for those from India, the average values of AUC and C max increase approximately 1.3-fold. Pharmacokinetic analysis among different ethnic groups did not reveal clinically significant differences in the pharmacokinetics of Europeans and black patients.

Renal failure.

The data of the study with participation of patients with renal insufficiency of various severity indicate that the kidney disease from low to moderate severity does not affect the concentration of rosuvastatin and its metabolite N-dimethyl, in blood plasma. In patients with a high degree of severity (KlKp <30 ml / min), the concentration of rosuvastatin in blood plasma is 3 times higher, and the concentration of N-dimethyl is 9 times higher than in healthy volunteers. The concentration of rosuvastatin in a state of dynamic equilibrium in the blood plasma of patients on hemodialysis is approximately 50% higher than that of healthy volunteers.

Liver failure.

Data from studies with patients with hepatic insufficiency of varying severity indicate that there is no increase in the effects of rosuvastatin in patients whose severity is estimated to be no higher than 7 on the Child-Pugh scale. However, in 2 patients with hepatic insufficiency of 8 and 9 on the Child-Pugh scale, there was an increase in the effect of rosuvastatin at least twice that of patients whose incidence is lower. The experience of using the drug in the therapy of patients with hepatic insufficiency of 9 points and higher on the Child-Pugh scale is absent.

Genetic polymorphism.

HMG-CoA reductase inhibitors, including rosuvastatin, bind to transport proteins OATP1B1 and BCRP. Patients with polymorphism of SLCO1B1 (OATP1B1) and / or ABCG2 (BCRP) genes have a risk of increased exposure to rosuvastatin. Individual polymorphism SLCO1B1 c.521CC and ABCG2 c.421AA associated with a corresponding increase in the exposure of rosuvastatin (AUC) is approximately 1.7 and 2.4 times compared with the genotypes SLCO1B1 c.521TT or ABCG2.

Application in pediatric practice.

Pharmacokinetic parameters when used in pediatric practice, namely when taken by patients aged 10 to 17 years with heterozygous familial hypercholesterolemia, are not exhaustively characterized. In a limited pharmacokinetic study using rosuvastatin (in tablets) to 18 pediatric patients, the impact indicators were consistent with those in adults. In addition, the results obtained indicate that there is no significant deviation from proportionality when taken in different doses.

Clinical characteristics

Indications

Adults

Treatment of hypercholesterolemia.

Primary hypercholesterolemia (type Iaa, including heterozygous familial hypercholesterolemia) or mixed dyslipidemia (type IIb) - as a supplement to a diet, when the effectiveness of a diet or other non-medicament means (eg exercise, weight loss) is not enough.

Homozygous familial hypercholesterolemia - as a supplement to the diet and other lipid-lowering medications (eg, low-density lipoprotein apheresis), or in cases where such treatments are not appropriate.

Prevention of cardiovascular disorders

Redistatin is indicated to reduce the risk of serious cardiovascular events in adults with an increased risk of developing atherosclerotic cardiovascular diseases, as evidenced by the presence of risk factors such as advanced age, hypertension, low HDL cholesterol, elevated C-reactive protein, smoking or having a family history of early development of coronary heart disease.

Treatment of atherosclerosis

The drug is prescribed to slow or stop the progression of the disease in patients who are shown to have lipid-lowering drugs.

Children and adolescents (from 10 to 17 years: boys - stage II and above on the Tanner scale, girls - at least one year after the first menstruation).

Treatment of primary hypercholesterolemia (type Pa) or mixed dyslipidemia (type IBb) due to heterozygous familial hypercholesterolemia is in addition to a diet when the effectiveness of a diet or other non-medicament methods (eg exercise, weight loss) is not enough.

Contraindications

  • Hypersensitivity to rosuvastatin or to any of the excipients;
  • liver disease in the active phase, including unknown etiology, persistent increase in the level of transaminases in the blood serum and the level of any transaminase more than 3 times higher than the upper limit of the norm (VMN)
  • severe renal dysfunction (creatinine clearance <30 mL / min);
  • myopathy;
  • simultaneous application of cyclosporine;
  • during pregnancy and lactation, as well as women of childbearing age who do not use appropriate contraceptives.

A dose of 40 mg is contraindicated in patients with factors contributing to the development of myopathy / rhabdomyolysis. These include:

  • impaired renal function of moderate severity (creatinine clearance <60 ml / min);
  • hypothyroidism
  • presence in an individual or family anamnesis of hereditary muscle diseases;
  • presence in the anamnesis of myotoxicity caused by other inhibitors of HMG-CoA reductase or fibrates;
  • alcohol abuse;
  • situations that may lead to an increase in the concentration of the drug in the plasma;
  • the patient's belonging to the Asian race;
  • simultaneous application of fibrates.

Interaction with other drugs and other interactions

Fenofibrates, derivatives of fibrous acid. Although no pharmacokinetic interaction between rosuvastatin and fenofibrate has been observed, pharmacodynamic interaction may occur. Gemfibrozil, fenofibrate and other fibroblasts of acid, including nicotinic acid, increase the risk of myopathy while being administered with HMG-CoA reductase inhibitors.

Cyclosporine. With simultaneous application of rosuvastatin and cyclosporine, the AUC (area under the curve) of rosuvastatin was on average 7 times higher than that of healthy volunteers. The concentration of cyclosporine in the blood plasma did not change at the same time.

Vitamin K antagonists. As with other HMG-CoA reductase inhibitors, at the beginning of therapy or with an increase in the dose of rosuvastatin in patients who simultaneously receive vitamin K antagonists (for example, warfarin or other indirect anticoagulants), PV may increase. The abolition of therapy with rosuvastatin or a reduced dose may provide a reduction in the international standardized ratio (INR). In such cases, it is recommended that the INR indicators be properly monitored.

Gemfibrozil and other lipid-lowering drugs. Simultaneous application of rosuvastatin and gemfibrozil leads to an increase in the values of C max and AUC rosuvastatin in 2 times.

According to the data of studies of specific interactions with drugs, no significant pharmacokinetic interaction with fenofibrate is expected, but pharmacodynamic interaction is not excluded. Gemfibrozil, fenofibrates, other fibrates and niacin (nicotinic acid) in a dose that is used to reduce the lipid content (≥ 1 g / day) increase the risk of myopathy with concomitant use with HMG-CoA reductase inhibitors, that these drugs themselves can cause myopathy. The use of the drug in a dose of 40 mg is contraindicated in the simultaneous administration of fibrates. Such patients are advised to start taking the drug at a dose of 5 mg per day.

Ezetimi would. With simultaneous administration of rosuvastatin and ezetimibe, AUC and C max of one of the drugs do not change. However, the possibility of pharmacodynamic interaction between rosuvastatin and ezetimibe, which leads to the development of side effects, is not ruled out.

Protease inhibitors. Although the exact mechanism of interaction is unknown, with the simultaneous administration of protease inhibitors, a significant increase in the effects of rosuvastatin is possible. According to the pharmacokinetic study, with simultaneous administration of rosuvastatin 20 mg and a combined preparation containing two protease inhibitors (400 mg of lopinavir / 100 mg of ritonavir), healthy volunteers showed an increase in the AUC (0-24) of rosuvastatin in a state of dynamic equilibrium in half, and of the C max index - 5 times. Thus, simultaneous use of rosuvastatin in the therapy of HIV patients receiving protease inhibitors is not recommended.

Antacids. The simultaneous administration of rosuvastatin and a suspension of antacids containing aluminum and magnesium hydroxide led to a 50% drop in rosuvastatin in the blood plasma. This effect is less pronounced if antacids are taken at 2:00 after taking rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin. Simultaneous application of rosuvastatin and erythromycin leads to a 20% decrease in AUC (0-t), and rosuvastatin C max value by 30%. This interaction is probably the result of increased intestinal motility caused by the administration of erythromycin.

Oral contraceptives / hormone replacement therapy (HRT). The simultaneous administration of rosuvastatin and oral contraceptives leads to an increase in the AUC value of ethinylestradiol and norgestrel by 26% and 34%, respectively.Such an increase in plasma concentration should be considered when choosing the appropriate dose of a contraceptive for oral use. Pharmacokinetic data on the administration of rosuvastatin against hormone replacement therapy (HRT) are absent, therefore, a similar effect is not excluded. However, this combination was widely used by women in clinical trials and was well tolerated.

Other medicines. According to studies of specific interaction with drugs, clinically significant interaction with digoxin is not expected.

Enzymes of the cytochrome P450 system. The results of in vitro and in vivo studies indicate that rosuvastatin does not cause an inhibitory or stimulating effect on cytochrome P450 isoenzymes. In addition, rosuvastatin is a poor substrate for these isoenzymes. There was no clinically significant interaction between rosuvastatin and fluconazole (an inhibitor of the enzymes CYP2C9 and CYP3A4) or ketoconazole (inhibitor of the enzymes CYP2A6 and CYP3A4). With simultaneous application of rosuvastatin and itraconazole (inhibitor of CYP3A4 enzymes), the values of AUC of rosuvastatin increase by 28%. Such a slight increase is not considered clinically significant. Thus, the drug interactions caused by changes in the activity of the enzymes of the cytochrome P450 system are not expected.

Application features

From the side of the kidneys

Proteinuria of tubular origin, determined from the analysis, was observed with rosuvastatin in high doses, especially 40 mg, although in most cases the disturbances were temporary. It is proved that proteinuria is not evidence of the development of acute or progression of the existing kidney disease. The frequency of serious violations in the kidneys is increased taking the drug at a dose of 40 mg. In the case of drug administration at a dose of 40 mg in the standard monitoring program must necessarily include a check renal function.

On the part of the skeletal muscles

On the part of the skeletal muscles, such as myalgia, myopathy and, often, rhabdomyolysis, have been observed in patients receiving rosuvastatin patients at any dose, usually when taken in doses> 20 mg. Very rarely reported cases of rhabdomyolysis the combined use of ezetimibe and HMG-CoA reductase inhibitors. Not excluded pharmacodynamic interaction therefore the combined use of preparations need special care.

As in the case of other HMG-CoA reductase, the incidence of rhabdomyolysis while taking rosuvastatin increases when it is applied in a dose of 40 mg. There are reports of rare cases of immune-mediated necrotizing myopathy manifested clinically resistant proksizmalnoyu muscle weakness and increased levels of serum CK, during treatment or after discontinuation of treatment with statins, including rosuvastatin. In this case, you may need additional neuromuscular and serologic studies, treatment with immunosuppressive drugs.

Determination of CK levels

Determination of CK should not be performed after vigorous exercise or the presence of other possible causes of increased CPK concentrations, which may distort the results. In the case of increasing concentrations of CPK (CPK) before therapy (> 5 × BMH) redetermine to verify the result should be conducted after 5-7 days. If the re-analysis results confirm the preliminary results upconcentration CPK (> 5 × BMH), treatment should not begin.

Prior to initiating therapy

Rosuvastatin, as well as other HMG-CoA reductase inhibitor should be used with caution in patients undergoing therapy prone to myopathy / rhabdomyolysis. Risk factors for developing myopathy / rhabdomyolysis are:

  • impaired renal function;
  • hypothyroidism
  • in the presence of a personal or family history of hereditary muscular diseases;
  • a history of muscle toxicity cases when using other HMG-CoA reductase inhibitors or fibrates;
  • alcohol abuse;
  • age> 70 years;
  • the situation in which may increase the plasma concentration
  • concurrent use of fibrates.

Assigning a drug to such patients should be carefully weighed risk ratio resulting from therapy, and the possible use; constant recommended clinical monitoring. In case of increase of CPK concentration before treatment (> 5 × BMH) treatment should not begin.

During therapy

Patients should inform the doctor immediately in case of obscure muscle pain, muscle weakness or cramps, especially if these phenomena are accompanied by malaise or fever. In such cases, the need to check the level of CK. Therapy should cancel with a significant increase in the concentration level of CK (> 5 × BMH) or high severity symptoms of the muscles which cause discomfort (even at a concentration level of CK (≤ 5x BMH). After elimination of symptoms and return the contents of CK within the rules can consider resuming therapy rosuvastatin or alternative drugs inhibitors of HMG-CoA reductase in most dose and when properly monitoring the patient. Constant monitoring CPK levels at absence of symptoms is not necessary.

An increased incidence of myopathy and myositis patients treated with other inhibitors of HMG-CoA reductase inhibitors together with fibric acid derivatives including gemfibrozil, cyclosporin, nicotinic acid preparations, azole antifungal agents, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy while the use of some HMG-CoA reductase. Thus, the simultaneous use of rosuvastatin and gemfibrozil is not recommended. The expediency of simultaneous reception of rosuvastatin and fibrates or niacin should be carefully weighed considering the potential risk. Purpose of the drug at a dose of 40 mg while receiving fibrates contraindicated.

Rosuvastatin should not be applied in the case of acute conditions, characteristic myopathy, or renal failure caused by rhabdomyolysis (e.g., in sepsis, hypotension, conducting extensive surgery, trauma, metabolic disorders, endocrine disorders, disorders of electrolyte balance-severe or uncontrolled epilepsy).

Liver

As with other inhibitors of HMG-CoA reductase Redistatin should be used with caution in the treatment of patients abusing alcohol and / or a history of liver disease have.

It is recommended to carry out analyzes to determine liver functions prior to as well as after 3 months after initiation of therapy. Further reception of rosuvastatin should cancel or reduce the dose of the drug in cases where the level of serum transaminases to more than 3 times the upper limit of normal. The incidence of serious disorders of the liver (which is preferably displays increased liver transaminase) in the period after the registration of the drug in patients receiving the above formulation at a dose of 40 mg.

If a patient secondary hypercholesterolemia due to hypothyroidism or nephrotic syndrome before treatment with rosuvastatin should cure the underlying disease.

Race

In pharmacokinetic studies there was an increase of systemic exposure in patients Asian race compared with Europeans.

protease inhibitors

Simultaneous application of the drug to the protease inhibitors are not recommended.

lactose intolerance

Redistatin formulation contains lactose. Patients with rare hereditary disorders such as galactose intolerance, lactase deficiency or malabsorption of glucose-galactose, should not be given this drug.

Interstitial lung disease

There have been reports of isolated cases of interstitial lung disease while taking certain drugs from the statins group, especially during prolonged therapy. Symptoms of the disease may be shortness of breath, nonproductive cough and deterioration of general health (fatigue, weight loss and fever). For suspected development of interstitial lung disease therapy with statins should be canceled.

Diabetes

As is the case with other inhibitors of HMG-CoA reductase inhibitor rosuvastatin observed when applying growth HbA1c and glucose level in blood serum. In some cases, these figures may exceed the limit value for the diagnosis of diabetes, especially in patients at high risk of developing diabetes.

from 10 to 17 years, children and adolescents

Determination of growth, weight, BMI (body mass index) and the formation of secondary signs of sexual development at Tanner scale in adolescents aged 10 to 17 years in patients receiving rosuvastatin is limited to a period of 1 year. After completion of 52 weeks of treatment with growth rates of deviation, body weight, BMI, and sex development have not been marked. Experience in the use of rosuvastatin in clinical studies involving children and adolescents is limited, the impact of the drug on the sexual development of long-term use (more than 1 year) is not known.

allergic reactions

Redistatin Tablets 10 mg, 20 mg and 40 mg contain in their composition the dye sunset yellow FCF, which may cause allergic reactions.

Use during pregnancy or lactation.

The use of rosuvastatin during pregnancy and breast-feeding is contraindicated.

Women of childbearing age should use reliable contraceptives.

Since cholesterol and other products of cholesterol biosynthesis are important for the development of the fetus, the potential risk of inhibition of HMG-CoA reductase inhibitors in pregnancy prevails benefit from therapy. The data obtained from the results of animal studies suggest a limited delayed toxic effects. In the case of pregnancy further therapy during treatment should be discontinued immediately.

Data on contact with the drug in breast milk are no women.

The ability to influence the reaction rate when driving vehicles or other mechanisms.

Investigation of the effect of the drug on Redistatin ability to drive or other mechanism is not performed. When driving vehicles or using other mechanisms should take into account the possibility of dizziness, which sometimes occurs during therapy.

Dosing and Administration

Before treatment, the patient must assign a standard holesterinsnizhayuschey diet to be followed and during therapy. Dose picked individually, taking into account the goal of therapy and response to it, following the current recommendations.

Redistatin can be taken at any time of the day, regardless of meals.

treatment of hypercholesterolemia

The recommended starting dose is 5 mg or 10 mg orally once a day for patients not treated with statin drugs earlier and patients previously treated with other inhibitors of HMG-CoA reductase. When selecting the initial dose should be taken into account individual indicators such as cholesterol levels and the risk of side effects from the cardiovascular system, as well as the risk of side effects. dosage adjustment is carried with its increase at 4 weeks as needed. Because of the increased incidence of adverse reactions when taking the drug at a dose of 40 mg compared with lower doses before dose escalation to 40 mg is recommended only in patients with high severity hypercholesterolemia are at high risk from the effects of the cardiovascular system,when the drug at a dose of 20 mg per day, does not provide the desired result, provided that the regular medical supervision. The drug in a dose of 40 mg is recommended to carry out under the supervision of a specialist.

Prevention of violations of the cardiovascular system

In a study on the risk of reducing the impact of drug complications from cardiovascular medication was applied at a dose of 20 mg per day. In patients with hypercholesterolemia necessary to carry out a standard definition of lipid levels, will also need to comply with dosing recommendations for the treatment of hypercholesterolemia.

The use in the treatment of elderly patients

For persons aged 70 years, the recommended dose is 5 mg. Further dose adjustment, due to the age of the patient is required.

Children aged 10 to 17 years (boys - on reaching the pubertal development stage I or higher Tanner, girl - no earlier than 1 year after menarche).

Babies are usually administered in an initial dose of 5 mg per day. The usual dosage range - 5-20 mg orally once daily. Increasing the dose is carried out with the individual response and tolerability, as recommended for use in pediatric practice. Before starting therapy with rosuvastatin child should designate the standard diet low in cholesterol; diet should be followed during the therapy. The safety and efficacy of the drug in doses of 20 mg in the treatment of this population were not investigated. Tablets of 40 mg are not intended for use in pediatric practice.

The use in the treatment of individuals with renal insufficiency

Adjusting the dose when using the drug in the treatment of patients with impaired kidney function or a low to moderate severity is not required.

In applying the drug therapy in patients with moderate severity of renal function (creatinine clearance <60 mL / min), the recommended initial dose should be 5 mg. Use of the drug at a dose of 40 mg is contraindicated in patients with impaired renal function moderate severity. Use of rosuvastatin in patients with impaired therapy high severity of renal function is contraindicated in any dose.

The use in the treatment of individuals with liver failure

Increased performance of the system while taking the influence of rosuvastatin in patients with hepatic insufficiency extent 7 Child-Pugh or less were not observed. However, upon receipt of patients with hepatic failure degree 8 and 9 to Child-Pugh observed increase system performance impact of rosuvastatin. In the treatment of these patients should also regularly check the kidney function. Experience with the drug in the treatment of patients with hepatic insufficiency higher degree of 9 on the scale of Child-Pugh no. The use of rosuvastatin therapy in patients with active liver disease is contraindicated. Patients with severe hepatic impairment observed increase rosuvastatin exposure, so they apply Redistatin at a dose higher than 10 mg should be cautious.

Ethnicity

In the Asian race of the patients had an increased systemic exposure of the drug. The recommended starting dose for patients of Asian origin is 5 mg. Application of a 40 mg dose is contraindicated in these patients. The maximum daily dose is 20 mg.

The dosage regimen in the treatment of patients who are prone to myopathy

The recommended initial dose therapy in patients who are prone to myopathy is 5 mg. Use of the drug at a dose of 40 mg is contraindicated in these patients. The maximum daily dose is 20 mg.

genetic polymorphism

Genotypes SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA compared with genotypes SLCO1B1 c.521TT and ABCG2 c.421CC, associated with an increase in exposure (AUC) of rosuvastatin. For patients with genotypes c.521CC or c.421AA maximum recommended daily dose is 20 mg Redistatinu.

Rosuvastatin is a substrate for various transport proteins (eg, OATP1B1 and BCRP). The risk of myopathy (including rhabdomyolysis) increases with simultaneous administration of the drug Redistatin along with certain drugs that can increase the plasma concentrations of rosuvastatin through interaction with these transport proteins (eg, cyclosporine and some protease inhibitors, including combinations of ritonavir with atazanavir, lopinavir and / or tipranavir ). In such cases, alternative treatment should be considered and, if necessary, temporarily discontinued. In situations where simultaneous administration of these drugs along with the drug Redistatin can not be avoided, it is necessary to weigh all the benefits and risks of concomitant treatment and carefully select the dose of the drug.

Children

It is not recommended to use the drug for children under 10 years.

The effect of rosuvastatin on linear growth (growth), body weight, BMI (body mass index) and the development of secondary sexual characteristics on the Tanner scores at the age of 10-17 years was estimated only for 1 year. After 52 weeks of the study drug, no effect on growth, body weight, BMI, or sexual development was detected.

Overdose

In case of an overdose, the patient should be given symptomatic treatment, if necessary, support therapy should be provided. It is necessary to monitor liver function and the level of CK. Carrying out of hemodialysis is inexpedient.

Adverse Reactions

Adverse reactions observed with the drug are usually mild and transient. Less than 4% of patients taking rosuvastatin in controlled clinical trials discontinued treatment due to the development of adverse reactions. The number of discontinuation cases was comparable to that of patients taking placebo. Adverse reactions are given below according to the frequency of occurrence: very often (≥ 1/10), often (≥ 1/100 to <1/10), infrequently (≥ 1/1000 <1/100), rarely (≥ 1/10000 <1/1000), very rarely (<1/10000), the frequency is unknown (can not be determined from available data).

From the immune system

Rarely, hypersensitivity reactions, including angioedema.

From the endocrine system

Often diabetes.

From the nervous system

Often: headache, dizziness.

From the gastrointestinal tract

Often constipation, nausea, pain in the abdomen.

Rarely pancreatitis.

From the skin and appendages

Infrequent: itching, rash, hives.

From the musculoskeletal system of connective tissues and bones

Often myalgia.

Rarely, myopathy (including myositis) and rhabdomyolysis.

Systemic disorders

Often asthenia.

As with other HMG-CoA reductase inhibitors, the incidence of adverse reactions depends on the dose of the drug.

On the part of the kidneys, when taking rosuvastatin, proteinuria of tubular origin, determined by the results of the analysis, was observed. An increase in the protein content in the urine from a complete absence or insignificant amount to ++ and more at different stages of therapy was observed in <1% of patients receiving the drug at a dose of 10 and 20 mg and approximately 3% of patients receiving the drug at a dose of 40 mg. A slight increase in the content from a complete absence or a small amount of up to + was observed when the preparation was given in a dose of 20 mg. In most cases, the manifestations of proteinuria decreased or disappeared independently on the background of continuation of therapy.

From the side of skeletal muscles: myalgia, myopathy (including myositis) and rarely rhabdomyolysis, accompanied or not accompanied by acute renal insufficiency, were observed in patients receiving rosuvastatin at any doses, in particular at doses> 20 mg.

In patients receiving rosuvastatin, there was a dose-dependent rise in the concentration of CK (CK). In most cases, the phenomenon was of low severity, was asymptomatic and of a transitory nature. If the concentration of CK is increased to> 5 × VMN, further therapy should be discontinued.

On the part of the liver: as with the administration of other HMG-CoA reductase inhibitors, an increase in transaminase activity, depending on the dose, was observed in a small number of patients receiving rosuvastatin. In most cases, the phenomenon was of low severity, was asymptomatic and of a transitory nature.

Impact on laboratory performance

As in the case of other HMG-CoA reductase inhibitors, a small number of patients taking rosuvastatin did not show a dose-proportional increase in the level of hepatic transaminases and CK. When rosuvastatin was used, there was also an increase in HbA1c levels. In a small number of patients who used Redistatin and other inhibitors of HMG-CoA reductase, pathological changes were observed in the analysis of urine (the test strip indicated proteinuria). The protein was found, as a rule, of tubular origin. In most cases, proteinuria becomes less pronounced or disappears spontaneously when continuing therapy and does not indicate an acute or progressive kidney disease.

Other effects

There is no evidence of harmful effects on the ocular lens.

In patients treated with the drug Redistatin, there was no abnormalities in the functions of the adrenal cortex.

Post-marketing experience

During the post-marketing application of rosuvastatin, the following side effects were observed.

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

On the part of the respiratory system: the frequency is unknown - cough, choking.

From the gastrointestinal tract: frequency is unknown - diarrhea.

From the hepatobiliary tract is very rare - jaundice, hepatitis is rare - increased activity of hepatic transaminases.

From the skin and subcutaneous tissue: the frequency is unknown - Stevens-Johnson syndrome.

From the musculoskeletal system: very rarely - arthralgia.

From the kidneys: rarely - hematuria.

Systemic abnormalities and disorders at the injection site: frequency unknown - swelling.

On the part of the reproductive system and mammary glands: the frequency is unknown - gynecomastia.

On the part of the blood: the frequency is unknown - thrombocytopenia.

Some statins reported such side effects:

Depression.

Sleep disturbance, including insomnia and nightmares.

Disorders of sexual function.

Individual cases of interstitial lung disease, especially in the case of prolonged therapy.

Diseases of the tendons, sometimes complicated by their rupture.

The incidence of rhabdomyolysis, severe renal and hepatic impairment (predominantly elevated transaminases) was higher with a dose of 40 mg.

Shelf life

2 years.

Storage conditions

Store at a temperature of no higher than 25 ° C, in the original packaging to protect against moisture. Keep out of the reach of children.

Packaging

10 tablets in a blister, 3 blisters in a cardboard box.

Category of leave

On prescription.


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