Suvardio film-coated tablets 10 mg blister No. 28

Instructions Suvardio film-coated tablets 10 mg blister No. 28

Composition

active ingredient: rosuvastatin;

1 tablet contains 5 mg or 10 mg or 20 mg of rosuvastatin (as rosuvastatin calcium);

excipients: anhydrous lactose, colloidal anhydrous silicon dioxide, silicified microcrystalline cellulose, corn starch, talc, sodium stearyl fumarate;

shell: hypromellose, mannitol (E 421), macrogol 6000, titanium dioxide (E 171), iron oxide yellow (E 172), iron oxide red (E 172), talc.

Dosage form

Film-coated tablets.

Main physicochemical properties:

5 mg tablets: round, light brown, film-coated tablets, embossed with “RSV 5” on one side;

10 mg tablets: round brown film-coated tablets, embossed with “RSV 10” on one side;

20 mg tablets: round brown film-coated tablets, embossed with “RSV 20” on one side.

Pharmacotherapeutic group

Lipid-lowering agents. HMG-CoA reductase inhibitors. ATC 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 to mevalonate, a precursor of cholesterol. The primary site of action of rosuvastatin is the liver, the target organ for cholesterol lowering.

Rosuvastatin increases the number of low-density lipoprotein (LDL) receptors on the surface of liver cells, increasing the uptake and catabolism of LDL, which in turn leads to inhibition of the synthesis of very low-density lipoprotein (VLDL), thereby reducing the total amount of LDL and VLDL. Rosuvastatin reduces elevated levels of LDL-cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) and increases the level of high-density lipoprotein (HDL-C). It also reduces the amount of apolipoprotein B (ApoB), non-HDL-C, VLDL-C, VLDL-TG and increases the level of apolipoprotein A-I (ApoA-I). Rosuvastatin also reduces the LDL-C/HDL-C ratio, total-C/HDL-C and non-HDL-C/HDL-C ratios, and the ApoB/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 is usually achieved after 4 weeks and is continuously maintained thereafter.

Pharmacokinetics

Absorption: Peak plasma concentrations of rosuvastatin are reached approximately 5 hours after oral administration. Absolute bioavailability is approximately 20%.

Distribution: Rosuvastatin is extensively taken up by the liver, which is the main site of cholesterol synthesis and LDL-C clearance. The volume of distribution of rosuvastatin is approximately 134 L. About 90% of rosuvastatin is bound to plasma proteins, mainly albumin.

Metabolism. Rosuvastatin undergoes minor metabolism (approximately 10%). In vitro metabolism studies using human hepatocytes indicate that rosuvastatin is a poor substrate for metabolism by cytochrome P450 enzymes. The main isoenzyme involved is CYP2C9, with 2C19, 3A4 and 2D6 playing a somewhat smaller role. The main identified metabolites are the N-desmethyl and lactone metabolites. The N-desmethyl metabolite is approximately 50% less active than rosuvastatin, the lactone metabolite is considered clinically inactive. Rosuvastatin accounts for more than 90% of the circulating HMG-CoA reductase inhibitory activity.

Elimination: Approximately 90% of the rosuvastatin dose is excreted unchanged in the feces (absorbed and unabsorbed active substance combined), the remainder is excreted in the urine. Approximately 5% is excreted unchanged in the urine. The plasma half-life is approximately 19 hours and does not increase with increasing dose. The geometric mean plasma clearance of the drug is approximately 50 l/h (coefficient of variation 21.7%). As with other HMG-CoA reductase inhibitors, hepatic uptake of rosuvastatin occurs with the participation of the membrane transporter OATP-C, 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 repeated daily administration.

Special patient groups.

Age and gender: There was no clinically significant effect of age or gender on the pharmacokinetics of rosuvastatin in adults. The pharmacokinetics of rosuvastatin in children and adolescents with heterozygous familial hypercholesterolemia were similar to those in adult volunteers (see section "Children").

Renal impairment. In a study of patients with varying degrees of renal impairment, no changes in plasma concentrations of rosuvastatin or its N-desmethyl metabolite were observed in subjects with mild or moderate renal impairment. In patients with severe renal impairment (creatinine clearance, N-desmethyl metabolite) the plasma concentrations were 9 times higher than in healthy volunteers. Steady-state plasma concentrations of rosuvastatin in patients on hemodialysis were approximately 50% higher than in healthy volunteers.

Hepatic impairment. In a study of patients with varying degrees of hepatic impairment, there was no evidence of increased exposure to rosuvastatin in patients with Child-Pugh scores of 7 or less. However, in two patients with Child-Pugh scores of 8 and 9, systemic exposure was at least twice as high as in patients with lower scores. There is no experience with rosuvastatin in patients with Child-Pugh scores greater than 9.

Genetic polymorphism. The distribution of HMG-CoA reductase inhibitors, including rosuvastatin, occurs with the participation of transport proteins OATP1B1 and BCRP. Patients with genetic polymorphisms of SLCO1B1 (OATP1B1) and/or ABCG2 (BCRP) are at risk of increased exposure to rosuvastatin. With certain forms of the SLCO1B1 p.521CC and ABCG2 p.421AA polymorphisms, rosuvastatin exposure (AUC) is increased compared with the SLCO1B1 p.521TT or ABCG2 p.421CC genotypes. Specific genotyping is not provided in clinical practice, but patients with such polymorphisms are recommended to use a lower daily dose of the drug.

Children: Two pharmacokinetic studies of rosuvastatin in children with heterozygous familial hypercholesterolemia aged 10 to 17 years and 6 to 17 years (total of 214 patients) showed that exposure in children was similar to or lower than that in adults. Exposure to rosuvastatin was predictable over a two-year period in terms of dose and time.

Indication

Treatment of hypercholesterolemia.

Adults, adolescents and children aged 10 years and over with primary hypercholesterolemia (type IIa) (excluding familial heterozygous hypercholesterolemia) or mixed dyslipidemia (type IIb) as an adjunct to diet therapy when diet or other non-pharmacological treatments (e.g. exercise, weight loss) are inadequate.

In homozygous familial hypercholesterolemia, as an adjunct to diet and other lipid-lowering measures (e.g., low-density lipoprotein apheresis) or in cases where such therapy is inappropriate.

Prevention of cardiovascular disorders.

Prevention of major cardiovascular events in patients estimated to be at high risk of a first cardiovascular event (see section 5.1), as an adjunct to correction of other risk factors.

Contraindication

- Hypersensitivity to rosuvastatin or to any of the excipients in the drug.

- Active liver disease, including persistent elevations of serum transaminases of unknown etiology, as well as elevations of serum transaminases exceeding the upper limit of normal (ULN) by more than 3 times.

- Severe renal impairment (creatinine clearance

- Myopathy.

- Concomitant use of cyclosporine.

- During pregnancy or breastfeeding, as well as for women of reproductive age who do not use appropriate contraception.

The 40 mg dose is contraindicated in patients with a predisposition to myopathy/rhabdomyolysis.

Such risk factors include:

- moderate renal impairment (creatinine clearance

- hypothyroidism;

- personal or family history of hereditary muscle diseases;

- history of muscle toxicity with other HMG-CoA reductase inhibitors or fibrates;

- alcohol abuse;

- situations that may lead to an increase in the concentration of the drug in the blood plasma;

- belonging to the Mongoloid race;

- concomitant use of fibrates.

Interaction with other medicinal products and other types of interactions

Effect of concomitant medications on rosuvastatin.

Inhibitors of transport proteins: Rosuvastatin is a substrate for certain transport proteins, including OATP1B1, which provides hepatic transport, and the efflux transporter BCRP. Co-administration of rosuvastatin with drugs that are inhibitors of these transport proteins may lead to increased plasma concentrations of rosuvastatin and an increased risk of myopathy (see Table 1).

Protease inhibitors. Although the exact mechanism of interaction is unknown, concomitant administration of protease inhibitors may result in a significant increase in rosuvastatin exposure. It is known that co-administration of rosuvastatin 10 mg with a combination of two protease inhibitors (300 mg atazanavir/100 mg ritonavir) to healthy volunteers resulted in a 2-fold increase in steady-state AUC(0-24) and a 7-fold increase in Cmax. Therefore, co-administration of rosuvastatin in HIV-infected patients receiving protease inhibitors is not recommended. Co-administration of rosuvastatin and some combinations of protease inhibitors may be considered after careful consideration of dose adjustments based on the expected increase in rosuvastatin exposure.

Gemfibrozil and other lipid-lowering agents. Simultaneous use of rosuvastatin and gemfibrozil leads to a 2-fold increase in Cmax and AUC of rosuvastatin.

Based on specific studies, no pharmacokinetically significant interaction is expected with fenofibrate, but a pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates, and niacin (nicotinic acid) in lipid-lowering doses (> or equal to 1 g/day) increase the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors, possibly because they can also cause myopathy when used alone. The use of the drug at a dose of 40 mg is contraindicated with simultaneous use of fibrates. It is recommended to start taking the drug in such patients with a dose of 5 mg per day.

Ezetimibe. Co-administration of rosuvastatin 10 mg and ezetimibe 10 mg in patients with hypercholesterolemia resulted in a 1.2-fold increase in rosuvastatin AUC. A pharmacodynamic interaction between rosuvastatin and ezetimibe, which could lead to adverse events, cannot be excluded.

Antacids. Co-administration of rosuvastatin with an antacid suspension containing aluminum and magnesium hydroxide resulted in a decrease in plasma concentrations of rosuvastatin by approximately 50%. This effect was reduced when the antacid was taken 2 hours after rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin. Concomitant use of rosuvastatin and erythromycin resulted in a 20% decrease in AUC(0-t) and a 30% decrease in Cmax of rosuvastatin. This interaction is likely due to increased intestinal motility caused by erythromycin.

Cytochrome P450 enzymes. In vitro and in vivo studies have shown that rosuvastatin has neither an inhibitory nor a stimulating effect on cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these isoenzymes. No clinically significant interaction was observed between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4 enzymes) or ketoconazole (an inhibitor of CYP2A6 and CYP3A4 enzymes).

Interactions requiring dose adjustment of rosuvastatin. When it is necessary to use rosuvastatin together with other drugs that increase its exposure, the dose of rosuvastatin should be adjusted. It should be started with a dose of 5 mg 1 time per day if an increase in exposure (AUC) of approximately 2 times or more is expected. The maximum daily dose of rosuvastatin should be adjusted so that the expected exposure does not exceed the concentration observed when taking a daily dose of 40 mg of rosuvastatin in the absence of drug interactions. For example, a dose of 5 mg of rosuvastatin with simultaneous use with cyclosporine (7.1-fold increase in exposure), a dose of 10 mg of rosuvastatin with simultaneous use with a combination of ritonavir/atazanavir (3.1-fold increase), and a dose of 20 mg of rosuvastatin with simultaneous use with gemfibrozil (1.9-fold increase).

Table 1

Effect of concomitant medications on rosuvastatin exposure (AUC; in descending order)

* Data presented as x-fold change represents the ratio between rosuvastatin in combination and alone. Data presented as % change represents the % difference relative to rosuvastatin alone.

Increase is indicated by the ↑ icon, no change is indicated by the ↔ icon, and decrease is indicated by the ↓ icon.

** Several interaction studies were conducted at different doses of the drug, the most significant ratio is presented in the table.

Effect of rosuvastatin on concomitant medications.

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 are simultaneously receiving vitamin K antagonists (for example, warfarin or other coumarin anticoagulants), an increase in the International Normalized Ratio (INR) may occur. Discontinuation of rosuvastatin therapy or dose reduction may result in a decrease in the INR. In such cases, appropriate monitoring of INR is recommended both at the beginning of treatment with rosuvastatin and after discontinuation or with subsequent changes in its dosage.

Oral contraceptives/hormone replacement therapy (HRT). Concomitant administration of rosuvastatin and oral contraceptives resulted in an increase in the AUC of ethinylestradiol and norgestrel by 26% and 34%, respectively. This increase in plasma concentrations should be considered when selecting an appropriate dose of oral contraceptive. Pharmacokinetic data on the use of rosuvastatin in combination with hormone replacement therapy (HRT) are not available, therefore a similar effect cannot be excluded. However, this combination has been widely used in women included in clinical trials and was well tolerated.

Other medicines.

Digoxin: Based on specific studies, no clinically significant interaction with digoxin is expected.

In clinical studies, rosuvastatin was used concomitantly with antihypertensives, antidiabetic agents, and hormone replacement therapy. These studies did not show any evidence of clinically significant adverse interactions.

Lopinavir/ritonavir: In a pharmacology study, co-administration of rosuvastatin and a combination product containing two protease inhibitors (lopinavir 400 mg/ritonavir 100 mg) in healthy volunteers was associated with an approximately two-fold and five-fold increase in steady-state AUC(0-24) and Cmax of rosuvastatin, respectively. Interactions between rosuvastatin and other protease inhibitors have not been studied.

Fusidic acid: The risk of myopathy, including rhabdomyolysis, may be increased when fusidic acid is administered concomitantly with statins. The mechanism of this interaction (pharmacodynamic, pharmacokinetic, or both pharmacodynamic and pharmacokinetic) is still unknown. There have been reports of rhabdomyolysis (including rare fatal cases) in patients receiving this combination.

If systemic use of fusidic acid is necessary, rosuvastatin treatment should be discontinued for the duration of fusidic acid administration (see section 4.4).

Children: Interaction studies have only been conducted in adults. The extent of interaction in children is unknown.

Application features

Kidney disorders.

Proteinuria of tubular origin, determined by the results of the analysis, was observed when using rosuvastatin in high doses, especially 40 mg, although in most cases the disorders were temporary and transient. It has been proven that proteinuria is not evidence of the development of acute or progression of existing kidney disease. The frequency of serious cases of renal impairment increases when taking the drug in a dose of 40 mg. When prescribing the drug in a dose of 40 mg, it is necessary to include a check of renal function in the standard monitoring program.

Skeletal muscle disorders.

Skeletal muscle disorders, such as myalgia, myopathy and, rarely, rhabdomyolysis, have been observed in patients taking rosuvastatin at all doses, most often at doses > 20 mg. Very rare cases of rhabdomyolysis have been reported with the combined use of ezetimibe and HMG-CoA reductase inhibitors. A pharmacodynamic interaction cannot be ruled out, therefore, special caution is required when using the drugs in combination.

As with other HMG-CoA reductase inhibitors, the incidence of rhabdomyolysis with rosuvastatin increases with a dose of 40 mg.

Creatine kinase (CK) levels should not be measured after significant exercise or in the presence of other probable causes of elevated CK levels, which may complicate interpretation of the results. In the event of a significant elevation of CK levels prior to initiation of therapy (> 5×ULN), a repeat test should be performed 5–7 days later to verify the result. If the results of the repeat test confirm the previous result of an elevation of CK levels > 5×ULN, treatment should not be initiated.

Before starting therapy.

Rosuvastatin, like other HMG-CoA reductase inhibitors, should be used with caution in patients with a predisposition to myopathy/rhabdomyolysis. Risk factors for the development of myopathy/rhabdomyolysis include: impaired renal function, hypothyroidism, personal or family history of hereditary muscle diseases, history of muscle toxicity with other HMG-CoA reductase inhibitors or fibrates, chronic alcoholism, age > 70 years, situations in which plasma concentrations of the drug may increase, concomitant use of fibrates. When prescribing the drug to such patients, the risk-benefit ratio of therapy should be carefully weighed; constant clinical monitoring is recommended. In the case of a significant increase in CK levels before the start of therapy (> 5 × ULN), treatment should not be started.

During therapy.

Patients should be advised to immediately report to their doctor any unexplained muscle pain, weakness or cramps, especially if accompanied by malaise or fever. In such cases, CK levels should be monitored. Therapy should be discontinued if CK levels are significantly elevated (> 5×ULN) or if muscle symptoms are severe enough to cause discomfort (even if CK levels are ≤ 5×ULN). Once symptoms have resolved and creatine kinase levels have returned to normal, resumption of therapy with rosuvastatin or alternative HMG-CoA reductase inhibitors at the lowest dose and with appropriate monitoring of the patient's condition may be considered. Continuous monitoring of CK levels is not necessary in the absence of symptoms.

Very rare cases of immune-mediated necrotizing myopathy (IMNM) have been reported during or after treatment with statins, including rosuvastatin. Clinical manifestations of IMM include proximal muscle weakness and elevated serum creatine kinase, which persist even after discontinuation of statins. In such cases, additional neuromuscular and serological studies, and treatment with immunosuppressive drugs may be necessary.

In clinical studies, there was no evidence of increased effects on skeletal muscle in a small number of patients taking rosuvastatin and concomitant medications. However, an increased incidence of myositis and myopathy has been reported in patients receiving other HMG-CoA reductase inhibitors in combination with fibric acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid preparations, azole antifungals, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when used concomitantly with some HMG-CoA reductase inhibitors. Therefore, concomitant use of rosuvastatin and gemfibrozil is not recommended. The benefits of further lipid-lowering effects of rosuvastatin and fibrates or niacin should be carefully weighed against the potential risks of such concomitant use. The use of the drug at a dose of 40 mg while taking fibrates is contraindicated.

Rosuvastatin should not be used concomitantly with systemic fusidic acid-containing products and within 7 days of stopping fusidic acid. Patients requiring systemic fusidic acid should discontinue statins for this period. Rhabdomyolysis (including rare fatal cases) has been reported in patients receiving fusidic acid in combination with statins. Patients should seek medical advice immediately if they experience symptoms of muscle weakness or muscle pain.

Statin therapy can be resumed 7 days after the last dose of fusidic acid.

In exceptional cases, if prolonged systemic use of fusidic acid is required, for example, for the treatment of severe infections, the need for the simultaneous use of rosuvastatin and fusidic acid should be considered in detail on a case-by-case basis under close medical supervision.

Rosuvastatin should not be used in the treatment of patients with severe acute conditions characteristic of myopathy or conditions that predispose to the development of renal failure due to rhabdomyolysis (e.g. sepsis, hypotension, major surgery, trauma, metabolic disorders, endocrine disorders, severe electrolyte imbalances or uncontrolled epilepsy).

Liver disorders.

It is recommended to conduct tests to determine liver function before the start of therapy, as well as 3 months after the start of therapy. Further use of rosuvastatin should be discontinued or the dose of the drug should be reduced in cases where the level of serum transaminases exceeds 3 times the upper limit of normal. The frequency of reports of serious liver disorders (manifested mainly by an increase in the level of hepatic transaminases) in the post-marketing period is higher when taking the drug at a dose of 40 mg.

If the patient has secondary hypercholesterolemia due to hypothyroidism or nephrotic syndrome, the underlying disease should be treated before starting rosuvastatin therapy.

In the post-marketing period, there have been rare reports of fatal or non-fatal cases of hepatic failure in patients taking statins, including rosuvastatin. If serious liver damage develops during treatment with rosuvastatin with clinical symptoms and/or hyperbilirubinemia or jaundice, the drug should be discontinued immediately. Unless other causes are identified, do not resume treatment with rosuvastatin.

Race.

In pharmacokinetic studies, an increase in systemic exposure and plasma concentrations of rosuvastatin was observed in patients of the Mongoloid race compared with Caucasians. For such patients, dosage adjustment of rosuvastatin is required; the initial dose of the drug should be 5 mg. The increased systemic exposure should be taken into account when treating patients of the Mongoloid race, in whom hypercholesterolemia is not adequately controlled with doses up to 20 mg.

Protease inhibitors.

Increased systemic exposure to rosuvastatin has been observed in subjects receiving rosuvastatin concomitantly with various protease inhibitors in combination with ritonavir. The benefit of lipid-lowering effects of rosuvastatin in HIV patients receiving protease inhibitors should be considered, as well as the possibility of increased plasma concentrations of rosuvastatin at the start of therapy and with dose increases in patients receiving protease inhibitors. Concomitant use of rosuvastatin with protease inhibitors is not recommended unless the dose of rosuvastatin is adjusted (see sections 4.2 and 4.5).

Interstitial lung disease.

There have been isolated reports of interstitial lung disease with some statins, particularly with long-term therapy. Symptoms may include shortness of breath, non-productive cough, and general ill health (fatigue, weight loss, and fever). If interstitial lung disease is suspected, statin therapy should be discontinued.

Diabetes.

There is some evidence that statins increase blood glucose levels and in some patients at high risk of future diabetes, may cause hyperglycemia to a level requiring appropriate diabetes management. However, this risk is outweighed by the reduced risk of vascular events with statins and should not be a reason to discontinue statin therapy. Patients at risk (fasting glucose 5.6-6.0 mmol/l, BMI >30 kg/m2, elevated triglycerides, hypertension) should be monitored both clinically and biochemically according to national guidelines.

In the studies, the overall incidence of diabetes mellitus was 2.8% in the rosuvastatin group and 2.3% in the placebo group, mainly in patients with fasting glucose levels between 5.6 and 6.9 mmol/L.

As with other HMG-CoA reductase inhibitors, increases in HbA1c and serum glucose levels have been observed with rosuvastatin. In some cases, these values may exceed the threshold for diagnosing diabetes mellitus, especially in patients at high risk of developing diabetes.

Studies have shown that rosuvastatin as monotherapy does not cause a decrease in basal plasma cortisol concentrations and does not affect adrenal reserve. Caution is required when rosuvastatin is used concomitantly with other drugs that may reduce the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone and cimetidine.

Children.

Assessment of linear growth (height), body weight, BMI (body mass index), and secondary Tanner puberty characteristics in children aged 10 to 17 years who received rosuvastatin was limited to a period of 1 year. After 52 weeks of study treatment, no effect on height, body weight, BMI, or puberty was observed.

In studies in children and adolescents taking rosuvastatin for 52 weeks, increases in CK levels > 10 × ULN and muscle symptoms after exercise or increased physical activity were observed more often compared to those in adults (see section "Adverse reactions").

Lactose intolerance.

This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicinal product contains sodium. Caution should be exercised when administered to patients on a controlled sodium diet.

Use during pregnancy or breastfeeding

The use of rosuvastatin during pregnancy or breastfeeding is contraindicated.

Women of reproductive age should use reliable contraception.

Since cholesterol and other cholesterol biosynthesis products are essential for fetal development, the potential risk of HMG-CoA reductase inhibition during pregnancy outweighs the benefit of therapy. Animal data suggest limited delayed toxicity. If pregnancy occurs during treatment with the drug, further therapy should be discontinued immediately.

Because another drug of this class is excreted in human milk and because HMG-CoA reductase inhibitors can cause serious adverse reactions in nursing infants, women requiring treatment with rosuvastatin should be advised to refrain from breast-feeding. There are no data on the excretion of rosuvastatin in human milk (see section 4.3).

Ability to influence reaction speed when driving vehicles or other mechanisms

Studies on the effect of rosuvastatin on the ability to drive or use machines have not been conducted. When driving or operating machinery, the possibility of dizziness during treatment should be taken into account.

Method of administration and doses

Before starting therapy, the patient should be placed on a standard cholesterol-lowering diet and should continue to follow it during therapy. Doses should be individualized according to the goal of therapy and response, in accordance with current consensus guidelines.

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

The tablet should not be chewed or crushed. The tablet should be swallowed whole with water.

Treatment of hypercholesterolemia.

The recommended starting dose is 5 or 10 mg orally once daily for patients who have not previously received statins or patients who have previously received other HMG-CoA reductase inhibitors. When choosing the starting dose, individual indicators such as cholesterol levels and the risk of future cardiovascular disorders, as well as the likelihood of developing adverse reactions, should be taken into account. Dose adjustment with an increase, if necessary, is carried out after 4 weeks. Due to the increased frequency of adverse reactions, an increase in the dose to 40 mg is recommended exclusively in the treatment of patients with severe hypercholesterolemia, at high risk of cardiovascular disorders (in particular, in patients with familial hypercholesterolemia), when taking the drug at a dose of 20 mg per day does not provide the desired result, subject to regular medical supervision.

Prevention of disorders of the cardiovascular system.

During the study of the drug's effect on reducing the risk of cardiovascular complications, the drug was used at a dose of 20 mg per day.

Elderly patients.

When using the drug in the treatment of people over 70 years of age, the recommended initial dose should be 5 mg. Further dose adjustment due to the patient's age is not required.

Patients with renal failure.

No dose adjustment is required when using the drug in the treatment of patients with mild or moderate renal impairment.

When using the drug in the treatment of patients with moderate renal impairment (creatinine clearance in the treatment of patients with severe renal impairment is contraindicated in any dose.

Patients with liver dysfunction.

In patients with hepatic impairment, assessed as 7 or less on the Child-Pugh scale, no increase in systemic exposure to rosuvastatin was observed. However, in subjects with impairment of 8