Rosuvastatin-SZ, pills 10mg, 60pcs

Composition

Active ingredient:  

rosuvastatin calcium in terms of rosuvastatin -10 mg.

Auxiliary substances:

core – lactose monohydrate (milk sugar) – 44,3 mg;

calcium hydrogen phosphate dihydrate – 10.0 mg;

povidone (polyvinylpyrrolidone middle) – 6.0 mg;

sodium krikellos (lamellosa) – 4.0 mg;

sodium fumarate to 1.2 mg;

silicon dioxide colloidal (Aerosil) – 0.5 mg;

cellulose microcrystalline – 44,0 mg;

shell Opadry II (polyvinyl alcohol, partially hydrolyzed – 1,76 mg; macrogol (polyethylene glycol) 3350 – 0,494 mg; talc – 0.8 mg; titanium dioxide E 171 – 0,7668 mg; soy lecithin E 322 – 0,14 mg; aluminum lacquer based on the dye Indigo Carmine – 0,0024 mg;aluminum lacquer dye azorubin – 0,0204 mg, aluminum lacquer based on dye crimson [Ponceau 4R] – 0,0164 mg).

Pharmacological action

Pharmacodynamics

Mechanism of action

Rosuvastatin is a selective, competitive inhibitor of HMG-CoA reductase, an enzyme that converts Z-hydroxy-Z-methylglugaryl coenzyme A to mevalonic acid, a precursor of cholchterin. The main target of rosuvastatin action is the liver, where the synthesis of cholesterol (cholesterol) and catabolism of low-density lipoproteins (LDL) is carried out.

Rosuvastatin increases the number of “hepatic” 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.

Pharmacodynamics

Rosuvastatin-SZ reduces elevated concentrations of LDL cholesterol (LDL-C), total cholesterol, triglycerides (TG), increases the concentration of high-density lipoprotein cholesterol (HDL-C), and also reduces the concentration of apolipoprotein B (apoB), HDL-C, VLDL – C, TG-VLDL and increases the concentration of apolipoprotein A-1 (ApoA-1), reduces the cx ratio of LDL-C/HDL-C, total cholesterol/HDL-C and non-HDL-C/HDL-C, and the apoB/ApoA-1 ratio.

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

Rosuvastatin-SZ is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia, regardless of race, gender or age, including in patients with diabetes mellitus and familial hypercholesterolemia.

In 80% of patients with hypercholesterolemia of Ha and HB type according to Fredrickson (the average initial concentration of LDL-C is about 4.8 mmol/l) against the background of taking the drug at a dose of 10 mg, the concentration of LDL-C dx reaches values of less than 3 mmol/l.

In patients with heterozygous familial hypercholesterolemia receiving Rosuvastatin-SZ at a dose of 20-80 mg, there is a positive dynamics in the lipid profile indicators. After titration to a daily dose of 40 mg (12 weeks of therapy), the LDL-C concentration decreased by 53%. In 33% of patients, an LDL-C concentration of less than 3 mmol/l is achieved.

In patients with homozygous familial hypercholesterolemia, taking Rosuvastatin-SZ at a dose of 20 mg and 40 mg, the average decrease in LDL-C concentration is 22%.

In patients with hypertriglyceridemia with an initial TG concentration of 273 to 817 mg/dp, who received Rosuvastatin-SZ at a dose of 5 mg to 40 mg once a day for 6 weeks, the concentration of TG in blood plasma significantly decreased.

An additive effect is observed in combination with fenofibrate in relation to the content of triglycerides and with nicotinic acid in lipid-lowering doses in relation to the content of HDL-C (see also the section “Special instructions”).

Based on the results of clinical studies, patients with severe hypercholesterolemia and a high risk of cardiovascular diseases (CVD) should be prescribed a dose of Rosuvastatin-SZ 40 mg.

The results of a clinical study (Justification for the use of statins for primary prevention: an interventional study evaluating rosuvastatin) showed that rosuvastatin significantly reduced the risk of developing cardiovascular complications. Pharmacokinetics Absorption and distribution

The maximum concentration of rosuvastatin in blood plasma is reached approximately 5 hours after oral use. The absolute bioavailability is approximately 20%. Rosuvastatin is primarily metabolized by the liver, which is the main site of cholesterol synthesis and LDL-C metabolism. The volume of distribution of rosuvastatin is approximately 134 liters. Approximately 90% of rosuvastatin binds to plasma proteins, mainly albumin.

Metabolism

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

The main identified metabolites of rosuvastatin are N-desmethylrosuvastagine and lactone metabolites. N-desmethylrosuvastatin is approximately 50% less active than rosuvastatin, and the lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity in inhibiting circulating HMG-CoA reductase is provided by rosuvastatin, the rest by its metabolites.

Deduction

Approximately 90% of the rosuvastatin dose is excreted unchanged through the intestine (including absorbed and unabsorbed rosuvastatin). The remaining part is excreted by the kidneys. The plasma half-life (Ti) is approximately 19 hours.

The half-life does not change with increasing dose of the drug. The average geometric plasma clearance is approximately 50 l / h (coefficient of variation 21.7%). As with other HMG-CoA reductase inhibitors, the process of” hepatic ” uptake of rosuvastatin involves a membrane cholesterol transporter, which plays an important role in the hepatic elimination of rosuvastatin.

Linearity

Systemic exposure to rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily use.

Special patient populations.

Age and gender

Gender and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin. Ethnic group

Pharmacokinetic studies showed approximately two-fold increase in median AUC (area under the curve “concentration-time”) and Cmax (maximum concentration in plasma) of rosuvastatin in patients of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with Caucasians; the Indians have shown an increase in median AUC and Cmax by 1.3 times. Pharmacokinetic analysis revealed no clinically significant differences in pharmacokinetics between Caucasians and Negroes.

Kidney failure

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

Liver failure

In patients with various stages of hepatic insufficiency, there was no increase in the half-life of rosuvastatin in patients with 7 points or lower on the Child-Pugh scale. In two patients with Child-Pugh scores 8 and 9, the elimination half-life increased by at least 2-fold. There is no experience of using rosuvastatin in patients with more than 9 points on the Child-Pugh scale.

Genetic polymorphism

HMG-CoA reductase inhibitors, including rosuvastatin, bind to the transport proteins OATP 1 In 1 (an organic anion transport polypeptide involved in the uptake of statins by hepatocytes) and BCRP (efflux transporter), and carriers of genotypes SLC01B1 (OATP 1 In 1) with 521 CC and ABCG2 (BCRP) with 421 AA showed an increase in exposure (AUC) to rosuvastatin increased by 1.6 and 2.4 times, respectively, compared with carriers of the SLC01B1 c. 521 TT and ABCG2 C. 421CC genotypes.

Indications

• Primary hypercholesterolemia according to the Fredrickson classification (type Na, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type HB) as an adjunct to diet, when diet and other non-drug treatments (for example, exercise, weight loss) are insufficient,

• Familial homozygous hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (for example, LDL apheresis), or in cases where such therapy is not effective enough,

• Hypertriglyceridemia (Fredrickson type IV) as a dietary supplement.

• To slow the progression of atherosclerosis as an adjunct to diet in patients who are indicated for therapy to reduce the concentration of total cholesterol and LDL-C.

• Primary prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of CHD, but with an increased risk of its development (age over 50 years for men and over 60 years for women, increased concentration of C-reactive protein (more than 2 mg / l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low HDL-C concentration, smoking, family history of early

Use during pregnancy and lactation

Rosuvastatin-SZ is contraindicated during pregnancy and lactation. Women of reproductive age should use adequate methods of contraception. Since cholesterol and other products of cholesterol biosynthesis are important for fetal development, the potential risk of HMG-CoA reductase inhibition exceeds the benefit of using the drug in pregnant women.

If pregnancy occurs during therapy, the drug should be discontinued immediately.

There are no data on the excretion of rosuvastatin in breast milk, so the drug should be discontinued during breastfeeding (see the section “Contraindications”).

Contraindications

For the drug Rosuvastatin-SZ in a daily dose of 5 mg. 10 mg and 20 mg:

• hypersensitivity to rosuvastatin or any of the components of the drug

• lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose)

• children under 18 years

• of age liver diseases in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times compared to the upper limit of normal)

• severe renal insufficiency (creatinine clearance less than 30 ml / min)

• myopathy

• concomitant use of cyclosporine

• in women: pregnancy; breastfeeding, lack of adequate methods of contraception

• increase the concentration of creatine phosphokinase (CPK) in the blood more than 5 times compared with the upper limit of normal

• combined use of inhibitors of the HIV protease

• patients predisposed to the development of myotoxicity complications of the drug Rosuvastatin-Sz in a daily dose of 40 mg:

• hypersensitivity to rosuvastatin or to any component of the drug

• lactose intolerance, lactase deficiency or glucose-galactose malabsorption (product contains lactose)

• children up to age 18 years,

• concomitant use of cyclosporine

• in women: pregnancy, breastfeeding, lack of adequate methods of contraception

• increase the concentration of creatine phosphokinase (CPK) in the blood more than 5 times compared with the upper limit of normal

• combined use of inhibitors of the HIV protease

• renal nedostatochno moderate and severe (CC less than 60 ml/min)

• liver diseases in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times the upper limit of normal) in patients with risk factors for myopathy/rhabdomyolysis, namely::

• hypothyroidism

• myotoxicity with other HMG-CoA reductase inhibitors or fibrates in the anamnesis

• excessive alcohol

• consumption conditions that may lead to increased plasma concentrations of rosuvastatin

• concomitant use of fibrates

• myopathy

• personal or family history of muscle diseases

• in patients of the Mongolian race

WITH CAUTION

For the drug Rosuvastatin-SZ in a daily dose of 5 mg,10 mg and 20 mg:

Risk of developing myopathy/rhabdomyolysis – renal failure, hypothyroidism, personal or family history of inherited muscle diseases and a previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates; excessive alcohol consumption; age over 65 years; conditions with increased plasma concentrations of rosuvastatin; race (Mongoloid race); concomitant use with fibrates (see the section “Risk factors”). Pharmacokinetics”); a history of liver disease; sepsis; hypotension; extensive surgery, trauma, severe metabolic, endocrine or electrolyte disorders, or uncontrolled seizures.

Concomitant use with colchicine and ezetimibe (see section “Interactions with other medicinal products”).

For the drug Rosuvastatin-SZ in a daily dose of 40 mg:

Mild renal insufficiency (creatinine clearance greater than 60 ml / min); age over 65 years; a history of liver disease; sepsis; hypotension; extensive surgery, trauma, severe metabolic, endocrine, or electrolyte disturbances, or uncontrolled seizures.

Concomitant use with colchicine and ezetimibe (see section “Interactions with other medicinal products”).

Patients with hepatic insufficiency

There are no data or experience of using the drug in patients with more than 9 points on the Child-Pugh scale (see the sections “Pharmacodynamics” and “Special instructions”).

Side effects

Side effects observed when taking the drug Rosuvastatin-SZ, usually expressed slightly and go away on their own. As with other HMG-CoA reductase inhibitors, the frequency of side effects is mainly dose-dependent. The frequency of occurrence of undesirable effects is presented as follows: often (> 1/100,1/1000,1/10000, >< 1/1000); very rare ( 

The immune system

Rarely: hypersensitivity reactions, including angioedema.

Endocrine System

Common: Type 2 diabetes mellitus

From the central nervous system

Often: headache, dizziness

From the digestive tract

Often: constipation, nausea, abdominal pain Rarely: pancreatitis

From the side of the skin

Infrequently: pruritus, rash, urticaria

Musculoskeletal disorders

Common: myalgia Rare: myopathy (including myositis), rhabdomyolysis

Other

Common: asthenic syndrome

From the urinary system

Patients treated with Rosuvastatin-SZ may develop proteinuria. Changes in the amount of protein in the urine (from no or trace amounts to ++ or more) are observed in less than 1% of patients receiving 10-20 mg of the drug, and in approximately 3% of patients receiving 40 mg of the drug. A slight change in the amount of protein in the urine was observed when taking a dose of 20 mg. In most cases, proteinuria decreases or disappears during therapy and does not indicate the occurrence of acute or progressive existing kidney disease.

From the musculoskeletal system

The following effects on the musculoskeletal system have been reported when Rosuvastatin-SZ is used in all doses and, in particular, when taking doses of the drug exceeding 20 mg: myalgia, myopathy (including myositis), in rare cases – rhabdomyolysis with or without acute renal insufficiency. A dose-dependent increase in creatine phosphokinase (CPK) activity is observed in a small number of patients taking rosuvastatin. In most cases, it was minor, asymptomatic, and temporary. In case of an increase in CPK activity (more than 5 times compared to the upper limit of normal), therapy should be suspended (see the section “Special instructions”).

From the liver

When using rosuvastatin, a dose-dependent increase in the activity of “hepatic” transaminases is observed in a small number of patients. In most cases, it is minor, asymptomatic, and temporary.

Laboratory parameters

When using Rosuvastatin-SZ, the following changes in laboratory parameters were also observed: increased glucose concentration, bilirubin, gamma-glutamyltranspeptidase activity, alkaline phosphatase, and thyroid function disorders.

Post-marketing application

The following side effects have been reported in post-marketing use of Rosuvastatin-SZ:

From the digestive tract

Very rare: jaundice, hepatitis Rare: increased activity of “hepatic” transaminases. Frequency unknown: diarrhea, fatal and non-fatal liver failure

From the musculoskeletal system

Very rare: arthralgia. Frequency unknown: immune-mediated necrotizing myopathy

From the central nervous system

Very rare: polyneuropathy, forgetfulness, amnesia, memory loss, respiratory confusion Frequency unknown: cough, shortness of breath

From the urinary system

Very rare: hematuria, microhematuria

From the skin and subcutaneous fat

Frequency unknown: Stevens-Johnson syndrome From the reproductive system and breast Frequency unknown: gynecomastia 

Other

Frequency unknown: peripheral edema; thrombocytopenia; interstitial lung disease. The following side effects have been reported with some statins: depression, sleep disorders including insomnia and nightmares, and sexual dysfunction.

Interaction

Effect of other drugs on Rosuvastatin transport protein inhibitors:Rosuvastatin binds to some transport proteins, in particular to OATP%^%1%^%B%^%1 and BCRP. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the concentration of rosuvastatin in plasma and an increased risk of developing myopathy (seesee table 1 and sections “Dosage and use” and “Special instructions”). Cyclosporine: when rosuvastatin and cyclosporine were co-administered, the AUC of rosuvastatin was on average 7 times higher than that observed in healthy volunteers (see table 1). It does not affect the plasma concentration of cyclosporine. Rosuvastatin-SZ is contraindicated in patients taking cyclosporine (see section “Contraindications”). Human immunodeficiency virus (HIV) protease inhibitors: Although the exact mechanism of interaction is unknown, co-use of HIV protease inhibitors can lead to a significant increase in rosuvastatin exposure. A pharmacokinetic study of concomitant use of 20 mg rosuvastatin with a combination drug containing two HIV protease inhibitors (400 mg lopinavir/100 mg ritonavir) in healthy volunteers resulted in approximately a twofold and fivefold increase in the AUC^ and Cmax of rosuvastatin, respectively. Therefore, simultaneous use of rosuvastatin and HIV protease inhibitors is not recommended (see sections “Dosage and use”, “Contraindications” and “Special instructions”). Gemfibrozil and other lipid-lowering agents: the combined use of rosuvastatin and gemfibrozil leads to a 2-fold increase in the maximum concentration of rosuvastatin in blood plasma and AUC of rosuvastatin (see the section “Special instructions”). Based on the specific interaction data, no pharmacokinetically significant interaction with fenofibrate is expected, and a pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid increased the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy when used in monotherapy (see section “Special instructions”). When taking the drug with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g/day), patients are recommended an initial dose of 5 mg, taking a dose of 40 mg is contraindicated when co-administered with fibrates (see sections “Contraindications”, “Method of use and doses”, “Special instructions”), Ezetimibe: simultaneous use of Rosuvastatin-SZ at a dose of 10 mg and ezetimibe at a dose of 10 mg It was accompanied by an increase in rosuvastatin AUC in patients with hypercholesterolemia (see Table 1). An increased risk of side effects due to the pharmacodynamic interaction between Rosuvastatin-SZ and ezetimibe cannot be excluded. Antacids: concomitant use of rosuvastatin and antacid suspensions containing aluminum and magnesium hydroxide leads to a decrease in the plasma concentration of rosuvastatin by approximately 50%. This effect is less pronounced if antacids are applied 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied. Erythromycin: concomitant use of rosuvastatin and erythromycin results in a 20% decrease in the AUC of rosuvastatin and rosuvastatin by 30%. This interaction may occur as a result of increased intestinal motility caused by taking erythromycin. Cytochrome P450 isoenzymes: In vivo and in vitro studies have shown that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, rosuvastatin is not expected to interact with other drugs at the level of metabolism involving cytochrome P450 isoenzymes. There was no clinically significant interaction of rosuvastatin with fluconazole (an inhibitor of the CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of the CYP2A6 and CYP3A4 isoenzymes). The dose of Rosuvastatin-SZ should be adjusted if it is necessary to use it together with drugs that increase exposure to rosuvastatin. If exposure is expected to increase by a factor of 2 or more, the initial dose of Rosuvastatin-SZ should be 5 mg once a day. It is also necessary to adjust the maximum daily dose of Rosuvastatin-SZ so that the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg taken without simultaneous use of drugs that interact with rosuvastatin. For example, the maximum daily dose of Rosuvastatin-SZ when used concomitantly with gemfibrozil is 20 mg (1.9-fold increase in exposure), with ritonavir/atazanavir-10 mg (3.1-fold increase in exposure). Effect of rosuvastatin on other vitamin K antagonist drugs: initiation of rosuvastatin therapy or an increase in the dose of the drug in patients receiving concomitant vitamin K antagonists (for example, warfarin) may lead to an increase in the International Normalized Ratio (INR). Discontinuation of rosuvastatin or a reduction in the dose of the drug may lead to a decrease in INR. In such cases, monitoring of INR is recommended. Oral contraceptives / hormone replacement therapy: concomitant use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively. Such an increase in plasma concentration should be taken into account when selecting the dose of oral contraceptives. Pharmacokinetic data on the simultaneous use of Rosuvastatin-SZ and hormone replacement therapy are not available, therefore, it is impossible to exclude a similar affect when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients. Other medicinal products: no clinically significant interaction of rosuvastatin with digoxin is expected.

How to take, course of use and dosage

Inside, do not chew or crush the tablet, swallow whole, filling with water. The drug can be prescribed at any time of the day, regardless of food intake.

Before starting therapy with Rosuvastatin-SZ, the patient should begin to follow a standard hypocholesterolemic diet and continue to follow it during treatment.

The dose of the drug should be selected individually, depending on the goals of therapy and the therapeutic response to treatment, taking into account current recommendations for target concentrations of lilides.

The recommended starting dose for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, should be 5 mg or 10 mg of Rosuvastatin-SZ 1 time per day. When choosing the initial dose, you should be guided by the individual cholesterol content and take into account the possible risk of cardiovascular complications, as well as the potential risk of side effects.

If necessary, the dose can be increased to a larger one after 4 weeks (see the section “Pharmacodynamics”).

Due to the possible development of side effects when taking a dose of 40 mg, compared with lower doses of the drug (see section “Side effects”), an increase in the dose to 40 mg, after an additional dose above the recommended initial dose for 4 weeks of therapy, can only be carried out in patients with severe hypercholesterolemia and at high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia), who did not achieve the desired result of therapy with a dose of 20 mg, and who will be under the supervision of a specialist (see section “Special Instructions”). Especially careful monitoring of patients receiving the drug at a dose of 40 mg is recommended.

It is not recommended to prescribe a dose of 40 mg to patients who have not previously consulted a doctor. After 2-4 weeks of therapy and/or with an increase in the dose of Rosuvastatin-SZ, monitoring of lipid metabolism parameters is necessary (if necessary, dose adjustment is required). Elderly patients Do not require dose adjustment.

Patients with renal insufficiency

No dose adjustment is required in patients with mild or moderate renal insufficiency. In patients with severe renal insufficiency (creatinine clearance less than 30 ml/min), the use of Rosuvastatin-SZ is contraindicated. It is contraindicated to use the drug at a dose of 40 mg in patients with moderate renal impairment (creatinine clearance 30-60 ml / min) (see sections “Special instructions” and “Pharmacodynamics”).

An initial dose of 5 mg is recommended for patients with moderate renal impairment

Patients with hepatic insufficiency

Rosuvastatin-SZ is contraindicated in patients with active liver diseases (see section “Contraindications”),

Special populations. Ethnic groups

When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, an increase in the systemic concentration of rosuvastatin among Japanese and Chinese was noted (see the section “Special instructions”).

This fact should be taken into account when prescribing Rosuvastatin-SZ to these groups of patients When prescribing doses of 10 mg and 20 mg, the recommended initial dose for patients of the Mongolian race is 5 mg. It is contraindicated to prescribe the drug at a dose of 40 mg to patients of the Mongolian race (see the section “Contraindications”),

Gdietic polymorphism

Carriers of the SLCOIBI (OATR 1V1) C. 521CC and ABCG2 (BCRP) C. 421AA genotypes showed increased exposure (AUC) to rosuvastatin compared to carriers of the SLCOIBI C. 521TT and ABCG2 C. 421 CC genotypes. For patients with C. 521 CC or C. 421 AA genotypes, the recommended maximum dose of Rosuvastatin-SZ is 20 mg once a day (see sections “Pharmacokinetics”, ” Special instructions “and”Interaction with other medicinal products”).

Patients predisposed to myopathy

It is contraindicated to prescribe the drug at a dose of 40 mg to patients with factors that may indicate a predisposition to the development of myopathy (seesection “Contraindications”). When prescribing doses of 10 mg and 20 mg, the recommended initial dose for this group of patients is 5 mg (see the section “Contraindications”),

Concomitant therapy

Rosuvastatin binds to various transport proteins (in particular, OATP1 In 1 and BCRP). When Rosuvastatin-SZ is co-administered with medicinal products (such as cyclosporine, certain HIV protease inhibitors, including ritonavir and atazanavir, lopinavir, and/or tipranavir) that increase the plasma concentration of rosuvastatin due to interaction with transport proteins, the risk of myopathy (including rhabdomyolysis) may increase (see sections “Special instructions” and “Interaction with other medicinal products”).

In such cases, the possibility of prescribing alternative therapy or temporarily stopping the use of Rosuvastatin-SZ should be evaluated. If the use of the above drugs is necessary, the benefit-risk ratio of concomitant therapy with the drug should be evaluated

Rosuvastatin-SZ and consider reducing its dose (see section “Interaction with other medicinal products”).

Overdose

With simultaneous use of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change. There is no specific treatment for rosuvastatin overdose.

In case of overdose, it is recommended to carry out symptomatic treatment and measures aimed at maintaining the functions of vital organs and systems.

Monitoring of liver function and CKD levels is necessary. It is unlikely that hemodialysis will be effective.

Special instructions

Renal effects

In patients receiving high doses of Rosuvastatin-SZ (mainly 40 mg), tubular proteinuria was observed, which in most cases was transient. Such proteinuria was not indicative of acute kidney disease or progressive kidney disease. In patients taking the drug at a dose of 40 mg, it is recommended to monitor the indicators of renal function during treatment.

From the musculoskeletal system

The following effects on the musculoskeletal system have been reported with the use of Rosuvastatin-SZ in all doses and, in particular, when taking doses of the drug exceeding 20 mg: myalgia, myopathy, and in rare cases rhabdomyolysis.

Determination of creatine phosphokinase

Determination of CKD activity should not be performed after intense physical exertion or in the presence of other possible causes of increased CKD activity, which may lead to misinterpretation of the results obtained. If the initial CPK activity is significantly increased (5 times higher than the upper limit of normal), a second measurement should be performed after 5-7 days. You should not start therapy if a repeated test confirms the initial CPK activity (more than 5 times higher than the upper limit of normal).

Before starting therapy

When prescribing Rosuvastatin-SZ, as well as when prescribing other HMG-CoA reductase inhibitors, caution should be exercised in patients with existing risk factors for myopathy/rhabdomyolysis (see the section “With caution”), it is necessary to consider the risk-benefit ratio of therapy and conduct clinical monitoring.

During therapy

The patient should be informed of the need to immediately inform the doctor about cases of unexpected muscle pain, muscle weakness or spasms, especially in combination with malaise and fever. In such patients, CPK activity should be determined. Therapy should be discontinued if CKD activity is significantly increased (more than 5 times higher than the upper limit of normal) or if muscle symptoms are severe and cause daily discomfort (even if CKD activity is 5 times lower than the upper limit of normal). If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing Rosuvastatin-SZ or other HMG-CoA reductase inhibitors in smaller doses, with careful monitoring of the patient.

Routine monitoring of CPK activity in the absence of symptoms is impractical.

Very rare cases of immune-mediated necrotizing myopathy have been reported with clinical manifestations of persistent weakness of the proximal muscles and increased serum creatinine clearance during treatment or upon discontinuation of statins, including rosuvastatin. Additional studies of the muscular and nervous system, serological studies, and immunosuppressive therapy may be required.

There were no signs of increased effects on skeletal muscle when taking Rosuvastatin-SZ and concomitant therapy. However, an increase in myositis and myopathy has been reported in patients treated with other HMG-CoA reductase inhibitors in combination with fibrinic acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid, azole antifungal agents, protease inhibitors, and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when co-administered with certain HMG-CoA reductase inhibitors. Therefore, the concomitant use of Rosuvastatin-SZ and gemfibrozil is not recommended. The risk-benefit ratio of Rosuvastatin-SZ and fibrate or lipid-lowering doses of nicotinic acid should be carefully weighed. It is contraindicated to take Rosuvastatin-SZ at a dose of 40 mg together with fibrates (see the sections “Interaction with other drugs” and “Contraindications”).

In 2-4 weeks after the start of treatment and/or with an increase in the dose of Rosuvastatin-SZ, monitoring of lipid metabolism parameters is necessary (if necessary, dose adjustment is required).

The liver

It is recommended to determine liver function indicators before the start of therapy and 3 months after the start of therapy. Rosuvastatin-SZ should be discontinued or the dose of the drug should be reduced if the activity of transaminases in the blood serum is 3 times higher than the upper limit of normal.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of the underlying diseases should be performed before starting treatment with Rosuvastatin-SZ.

Special populations. Ethnic groups

In the course of pharmacokinetic studies among Chinese and Japanese patients, an increase in the systemic concentration of rosuvastatin was noted compared with the indicators obtained among Caucasian patients (see the sections “Dosage and use” and “Pharmacokinetics”).

HIV protease inhibitors

Concomitant use of the drug with HIV protease inhibitors is not recommended (see the sections “Interaction with other drugs” and “Contraindications”).

Lactose

The drug should not be used in patients with lactase deficiency, galactose intolerance and glucose-galactose malabsorption.

Interstitial lung disease

Isolated cases of interstitial lung disease have been reported with the use of certain statins, especially for a long time. Symptoms of the disease may include shortness of breath, an unproductive cough, and poor overall health (weakness, weight loss, and fever). If interstitial lung disease is suspected, statin therapy should be discontinued.

Type 2 diabetes mellitus

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

Influence on the ability to drive motor vehicles and manage mechanisms

No studies have been conducted to study the effect of Rosuvastatin-SZ on the ability to drive a vehicle and use mechanisms. Caution should be exercised when driving vehicles or working at work that requires increased concentration of attention and speed of psychomotor reactions (dizziness may occur during therapy).

Form of production

Tablets covered with a film-coated pink color, round, biconvex.

On a cross-section, the tablet core is white or almost white in color.

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 30°C.

Shelf

life is 3 years. Do not use after the expiration date indicated on the package.

Active ingredient

Rosuvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets