Rosart, 40 mg 30 pcs.

Pharmacotherapeutic group

Hypolipidemic drug – HMG-CoA reductase inhibitor

ATX code: C10AA07

Pharmacological Properties

.Pharmacodynamics

Hypolipidemic drug from the group of statins. Selective competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase – the enzyme that converts HMG-CoA to mevalonate, a precursor of cholesterol.

increases the number of low-density lipoprotein (LDL) receptors on the surface of hepatocytes, which leads to increased capture and catabolism of LDL, inhibiting the synthesis of very low-density lipoprotein (VLDL), reducing the total amount of LDL and VLDL. Reduces elevated concentrations of LDL cholesterol, low-density lipoprotein cholesterol (non-LDL), LDL cholesterol, total cholesterol, triglycerides (TG), TG-LDL, apolipoprotein B (ApoB), decreases ratios of cholesterol-LDL/cholesterol-LDL, total cholesterol/cholesterol-LDL, cholesterol-non-LDL/cholesterol-LDL, apoB/apolipoprotein A-I (apoA-I), increases the concentration of cholesterol-LDL and apoA-I.

The hypolipidemic effect is directly proportional to the dose prescribed. The therapeutic effect appears within 1 week after the start of therapy, after 2 weeks it reaches 90% of the maximum, by 4 weeks it reaches the maximum and after that it remains constant. Effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia (regardless of race, sex or age), including patients with diabetes and familial hypercholesterolemia. In 80% of patients with hypercholesterolemia of IIa and IIb types (Fredrickson classification) with a mean baseline LDL-cholesterol index of about 4.8 mmol/l against the background of taking this medicine in dose 10 mg, LDL-cholesterol concentration reached values less than 3 mmol/l. In patients with homozygous familial hypercholesterolemia taking the drug in doses of 20 mg and 40 mg the average decrease of LDL-cholesterol concentration is 22%.

Additive effect is noted in combination with fenofibrate (with respect to decrease in TG concentration) and with nicotinic acid in lipid-lowering doses ≥1 g/day (with respect to increase in HDL cholesterol concentration).

Pharmacokinetics

Intake

The maximum concentration (C_max) of rosuvastatin in plasma is reached approximately 5 h after drug administration. Absolute bioavailability is approximately 20%. Systemic exposure of rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily administration.

Distribution

Rosuvastatin penetrates the placental barrier. Rosuvastatin is absorbed primarily by the liver, which is the main site of cholesterol synthesis and metabolism of LDL-C. The volume of distribution is 134 l. Binding to plasma proteins (predominantly to albumin) is approximately 90%.

Metabolism

Biotransformation in the liver is low (about 10%), being a non-core substrate for cytochrome P450 system isoenzymes. As in the case of other HMG-CoA reductase inhibitors, a specific membrane transporter, polypeptide transporting organic anion (OATP) 1B1, is involved in the hepatic uptake of the drug, which plays an important role in its hepatic elimination. The main isoenzyme involved in the metabolism of rosuvastatin is CYP2C9. CYP2C19, CYP3A4 and CYP2D6 isoenzymes are less involved in metabolism.

The main metabolites of rosuvastatin are N-desmethyl and lactone metabolites. N-desmethyl is about 50% less active than rosuvastatin; lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity for inhibition of circulating HMG-CoA reductase is provided by rosuvastatin, the rest by its metabolites.

Elimation

About 90% of the dose of rosuvastatin is excreted unchanged through the intestine, the remainder – by the kidneys. The elimination half-life (T_1/2) is approximately 19 h and does not change with increasing dose of the drug. Mean plasma clearance is approximately 50 l/h (coefficient of variation 21.7%).

In patients with mild to moderately severe renal impairment plasma concentrations of rosuvastatin or N-desmethyl do not change significantly. In patients with severe renal impairment (creatinine clearance (CK) less than 30 ml/min), plasma concentrations of rosuvastatin are 3 times higher and N-desmethyl are 9 times higher than in healthy volunteers. Plasma concentrations of rosuvastatin in patients on hemodialysis are approximately 50% higher than in healthy volunteers.

In patients with various stages of hepatic failure with a Child-Pugh score of 7 or lower, no increase in T_1/2 rosuvastatin; in patients with Child-Pugh scores 8 and 9 there was a prolongation of T_1/2 by 2 times. There is no experience of using the drug in patients with more severe liver dysfunction.

Gender and age have no clinically significant effect on the pharmacokinetics of rosuvastatin. Pharmacokinetic parameters depend on race: the area under the curve “concentration-time” (AUC) in Japanese and Chinese is 2 times higher than that in Europe and North America. The average value of AUC and C_max increases by a factor of 1.3 for mongoloids and Indians.

Indications

Active ingredient

Composition

1 tablet 5 mg contains:

Active substance: Calcium rosuvastatin 5.21 mg (in terms of rosuvastatin 5.00 mg);

Associated substances: Microcrystalline cellulose, type 102 11.55 mg, crospovidone, type A 3.50 mg, calcium hydrophosphate dihydrate 17.15 mg, lactose monohydrate 31.71 mg, magnesium stearate 0.88 mg;

Opadray white II 33G28435 ≈ 2.10 mg (hypromellose-2910 0.8400 mg, titanium dioxide 0.5250 mg, lactose monohydrate 0.4410 mg, macrogol-3350 0.1680 mg, triacetin 0.1260 mg).

1 tablet 10 mg contains:

The active ingredient: Calcium rosuvastatin 10.42 mg (in terms of rosuvastatin 10.00 mg);

Ancillary substances: Microcrystalline cellulose, type 102 23.10 mg, crospovidone, type A 7.00 mg, calcium hydrophosphate dihydrate 34.30 mg, lactose monohydrate 63.42 mg, magnesium stearate 1.76 mg;

Opadray pink II 33G240007 ≈ 4.20 mg (hypromellose-2910 1.6800 mg, titanium dioxide 1.0441 mg, lactose monohydrate 0.8820 mg, macrogol-3350 0.3360 mg, triacetin 0.2520 mg, carmine red dye 0.0059 mg).

1 tablet 20 mg contains:

Active substance: rosuvastatin calcium 20.84 mg (in terms of rosuvastatin 20.00 mg);

Associated substances: Microcrystalline cellulose, type 102 46.20 mg, crospovidone, type A 14.00 mg, calcium hydrophosphate dihydrate 68.60 mg, lactose monohydrate 126.84 mg, magnesium stearate 3.52 mg;

Opadray pink II 33G240007 ≈ 8.40 mg (hypromellose-2910 3.3600 mg, titanium dioxide 2.0882 mg, lactose monohydrate 1.7640 mg, macrogol-3350 0.6720 mg, triacetin 0.5040 mg, carmine red dye 0.0118 mg).

1 tablet 40 mg contains:

Active substance: rosuvastatin calcium 41.68 mg (in terms of rosuvastatin 40.00 mg);

Associated substances: Microcrystalline cellulose, type 102 92.40 mg, crospovidone, type A 28.00 mg, calcium hydrophosphate dihydrate 137.20 mg, lactose monohydrate 253.68 mg, magnesium stearate 7.04 mg;

Opadray pink II 33G240007 ≈ 16.80 mg (hypromellose-2910 6.7200 mg, titanium dioxide 4.1765 mg, lactose monohydrate 3.5280 mg, macrogol-3350 1.3440 mg, triacetin 1.0080 mg, carmine red dye 0.0235 mg).

How to take, the dosage

Overly, without chewing or crushing, swallowed whole with water, regardless of the time of day or meal.

The patient should start a standard hypolipidemic diet before starting therapy with Rosart and continue this diet during treatment. The dose of the drug should be adjusted individually depending on the indication and therapeutic response, taking into account current generally accepted recommendations for target lipid concentrations. The recommended starting dose of Rosart for patients starting to take the drug or for patients transferred from other HMG-CoA reductase inhibitors is 5 or 10 mg once daily. When choosing the initial dose, the patient’s cholesterol concentration should be guided and the risk of cardiovascular complications should be taken into account, and the potential risk of adverse reactions should be assessed. If necessary, the drug dose may be increased after 4 weeks.

With regard to the possible development of side effects at a dose of 40 mg compared to lower doses of the drug (see section “Side effects”).

Particularly in patients with severe hypercholesterolemia and high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia) who have not reached their target cholesterol concentration on the 20 mg dose and who will be under medical supervision, final titration to the maximum dose of 40 mg should only be performed.

Particular close monitoring of patients receiving the drug at a dose of 40 mg is recommended. After 2-4 weeks of therapy and/or increasing the dose of the drug, monitoring of lipid metabolism parameters is necessary.

In Elderly patients over 70 years of age, the recommended starting dose of Rosart is 5 mg; no other dose adjustment is required.

In patients with hepatic impairment with a Child-Pugh score less than 7, no dose adjustment is required. In patients with Child-Pugh scores 8 and 9 a preliminary assessment of renal function should be performed. There is no experience of using rosuvastatin in patients with hepatic impairment above a Child-Pugh score of 9. Rosuvastatin is contraindicated in patients with active liver disease.

In mild to moderate renal failure no dose adjustment is required. The recommended initial dose of the drug is 5 mg for patients with moderate renal failure (CKR less than 60 ml/min). Patients with moderate renal failure (CKD less than 30-60 ml/min) administration of the drug in dose of 40 mg is contraindicated. Administration of the drug Rosart is contraindicated in any dose in patients with severe renal failure (CKD less than 30 ml/min).

Ethnic groups

Mongoloid patients may have increased systemic rosuvastatin concentrations. Initial recommended dose of the drug for patients of mongoloid race is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in these patients.

Genetic polymorphism

Various genetic polymorphisms are known that may lead to increased systemic concentration of rosuvastatin. Lower daily doses of rosuvastatin are recommended in patients with identified specific polymorphisms.

Patients susceptible to myopathy

The initial recommended dose for these patients is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in these patients.

Combination therapy

Rosuvastatin is a substrate for various transport proteins (e.g., OATP1B1 and BCRP). The risk of myopathy, including rhabdomyolysis, increases with concomitant use of rosuvastatin with drugs that increase plasma concentrations of rosuvastatin due to their interaction with transport proteins. This group of substances includes cyclosporine, HIV protease inhibitors, including the combination of ritonavir with atazanavir, lopinavir and/or tipranavir; see sections Special indications and Interaction with other medicinal products). Whenever possible, a decision should be made to prescribe alternative therapy and, if necessary, temporarily discontinue rosuvastatin. If concomitant administration cannot be avoided, the possible risk of interaction and the potential benefit of concomitant treatment should be carefully evaluated (see section Interaction with other medicinal products).

Interaction

Influence of the use of other drugs on rosuvastatin

.Inhibitors of transport proteins

Rosuvastatin binds to some transport proteins, in particular OATP1B1 and BCRP. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by increased plasma concentrations of rosuvastatin and an increased risk of myopathy (see Table 1 and sections “Administration and Dose” and “Precautions”).

Cyclosporine

In concomitant use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was, on average, 7 times higher than that observed in healthy volunteers (see Table 1). Rosuvastatin has no effect on the plasma concentration of cyclosporine. Rosuvastatin is contraindicated in patients taking cyclosporine (see section “Contraindications”).

Human immunodeficiency virus (HIV)protease inhibitors

While the exact mechanism of interaction is unknown, concomitant use of HIV protease inhibitors and rosuvastatin may result in a significant increase in rosuvastatin exposure (see Table 1). A pharmacokinetic study of the 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 twofold and fivefold increases in AUC(0-24) and Cmax rosuvastatin, respectively. Therefore, concomitant use of rosuvastatin and HIV protease inhibitors is not recommended (see Table 1 and sections “Administration and Doses”, “Special Precautions”).

Hemfibrozil and other hypolipidemic agents

Concomitant use of rosuvastatin and gemfibrozil leads to a 2-fold increase in plasma Cmax and AUC of rosuvastatin (see sect. section “Special Indications”). Based on the data on specific interactions, no pharmacokinetic interaction is expected between rosuvastatin and fenofibrate, but pharmacodynamic interaction is possible.

Hemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid increased the risk of myopathy when used simultaneously with HMG-CoA reductase inhibitors, possibly due to the fact that these agents may cause myopathy when used in monotherapy (see section “Special Indications”). When concomitant administration of rosuvastatin with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g/day), a starting dose of 5 mg is recommended. It is contraindicated to take rosuvastatin in dose of 40 mg concomitantly with fibrates (see sections “Contraindications”, “Dosage and administration”, “Special indications”).

Ezetimibe

The concomitant use of rosuvastatin in dose of 10 mg and ezetimibe in dose
10 mg in patients with hypercholesterolemia resulted in increased AUC of rosuvastatin (see Table 1). An increased risk of side effects due to pharmacodynamic interaction between rosuvastatin and ezetimibe cannot be excluded.

Antacids

Concomitant use of rosuvastatin and suspensions of antacids containing magnesium hydroxide and aluminum hydroxide leads to a decrease in plasma concentration of rosuvastatin by approximately 50%. This effect is weaker if antacids are used 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.

Eritromycin

The concomitant use of rosuvastatin and erythromycin resulted in a 20% decrease in AUC of rosuvastatin and a 30% decrease in Cmax of rosuvastatin. This interaction may result from increased intestinal motility caused by taking erythromycin.

Cytochrome P450

The results of studies conducted in vivo and in vitro showed that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, no interaction of rosuvastatin with other drugs at the level of metabolism involving cytochrome P450 isoenzymes is expected. No clinically significant interaction of rosuvastatin with fluconazole (inhibitor of CYP2C9 and CYP3A4 isoenzymes) and rosuvastatin with ketoconazole (inhibitor of CYP2A6 and CYP3A4 isoenzymes) was observed.

Fusic acid

There have been no studies on the interaction between rosuvastatin and fusic acid. As with other statins, there have been post-marketing reports of cases of rhabdomyolysis when co-administering rosuvastatin and fusidic acid. Close monitoring of patients is necessary. If necessary, temporary discontinuation of rosuvastatin is possible.

Interaction with drugs requiring dose adjustment of rosuvastatin (see. Table 1)

If rosuvastatin must be used together with other drugs that increase rosuvastatin exposure, the dose of rosuvastatin should be adjusted. Read the instructions for use for these drugs before prescribing them together with rosuvastatin. The starting dose of rosuvastatin should be 5 mg once daily if the exposure (AUC) to rosuvastatin is expected to increase by a factor of 2 or more. The maximum daily dose of rosuvastatin should also be adjusted so that the expected exposure of rosuvastatin does not exceed that of a 40 mg dose taken without concomitant administration of drugs that interact with rosuvastatin. For example, when used concomitantly with gemfibrozil, the maximum daily dose of rosuvastatin is 20 mg (1.9-fold increase in exposure), when used with the combination ritonavir/atazanavir – 10 mg (3.1-fold increase in exposure).

Table 1. Effect of co-administered drugs on rosuvastatin exposure (AUC, in descending order of magnitude), according to published clinical trials.

.The dosing regimen of the interacting drug

Rosuvastatin dosing regimen

Change AUC

rosuvastatin

Cyclosporine 75-200 mg 2 times daily, 6 months

10 mg once daily, 10 days

7.1-fold increase

Regorafenib 160 mg once daily, 14 days

5 mg once

Increased 3.8 times

Atazanavir 300 mg/ritonavir 100 mg once daily, 8 days

10 mg once

A 3.1-fold increase

/td>

Simeprevir 150 mg once daily, 7 days

/p>

10 mg once

2.8-fold increase

Velpatasvir 100 mg once daily

10 mg once

Increase 2.8-fold.7 times

5 mg once

Increase 2.6 times

Grazoprevir 200 mg/ elbasvir 50 mg once daily, 11 days

/p>

10 mg once

Increase 2.3x

Glecaprevir 400 mg/pibrentasvir 120 mg once daily, 7 days

/p>

5 mg once daily, 7 days

Increase by 2.2 times

Lopinavir 400 mg/ritonavir 100 mg 2 times daily, 17 days

20 mg once, 7 days

2.1-fold increase

Clopidogrel 300 mg (loading dose) followed by 75 mg 24 hours later

20 mg once

Increase 2.0 times

Hemfibrozil 600 mg 2 times daily, 7 days

80 mg

once

1.9-fold increase

Eltrombopag 75 mg once daily, 10 days

/p>

10 mg once

Increased 1.6-fold

Darunavir 600 mg/ritonavir 100 mg 2 times daily, 7 days

10 mg once daily, 7 days

Increased 1.5 times

Tipranavir 500 mg/ritonavir 200 mg 2 times daily, 11 days

10m annually

1.4-fold increase

dronedarone 400 mg 2 times daily

No data

1.4-fold increase

Itraconazole 200 mg once daily, 5 days

10 mg or 80 mg once

1.4-fold increase

Ezetimibe 10 mg once daily, 14 days

/p>

10 mg once daily, 14 days

1.2-fold increase

Fosamprenavir 700 mg/ritonavir 100 mg twice daily, 8 days

10 mg once

No change

Aleglitazar 0.3 mg, 7 days

40 mg, 7 days

No change

Silymarin 140 mg 3 times daily, 5 days

10m annually

No change

Fenofibrate 67 mg 3 times daily, 7 days

/p>

10 mg, 7 days

No change

Rifampin 450 mg once daily, 7 days

20 mg once

No change

Ketoconazole 200 mg 2 times daily, 7 days

/p>

80 mg once

No change

Fluconazole 200 mg once daily, 11 days

80 mg once

/td>

No change

Erythromycin 500 mg 4 times daily, 7 days

/p>

80 mg once

28% reduction

Baicalin 50 mg 3 times daily, 14 days

20 mg once

47% reduction

.Effect of rosuvastatin use on other drugs

Vitamin K antagonists

The initiation of therapy with rosuvastatin or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (e.g., warfarin) may result in an increase in the international normalized ratio (INR). Discontinuation of rosuvastatin or reduction of its dose may lead to a decrease in INR. INR control is recommended in such cases.

The oral contraceptive/ hormone replacement therapy (HRT)

The concomitant use of rosuvastatin and oral contraceptives increases AUC of ethinylestradiol and AUC of norgestrel by 26% and 34%, respectively. This increase in plasma concentration should be considered when selecting a dose of oral contraceptives. There are no pharmacokinetic data on concomitant use of rosuvastatin and GZT, therefore, the occurrence of a similar effect cannot be excluded. However, this combination was widely used during clinical trials and was well tolerated by patients.

Other medications

No clinically significant interaction of rosuvastatin with digoxin is expected.

Special Instructions

Influence on renal function

In patients receiving high-dose rosuvastatin (mainly 40 mg), urinalysis with test strips showed tubular proteinuria, which in most cases was transient. Such proteinuria was not indicative of acute kidney disease or progression of renal disease. The frequency of reports of serious adverse renal reactions in the post-marketing period was higher in patients taking rosuvastatin at a dose of 40 mg.

When using Rosart in a dose of 40 mg, it is recommended to monitor renal function parameters during treatment.

Musculoskeletal effects

When using all doses of rosuvastatin and especially when taking doses greater than 20 mg, the development of myalgia, myopathy and, rarely, rhabdomyolysis has been reported. In very rare cases, the development of rhabdomyolysis has been reported when concomitant administration of HMG-CoA reductase inhibitors and ezetimibe. In this case, pharmacodynamic interaction cannot be excluded, so caution should be exercised when taking them together. As with other HMG-CoA reductase inhibitors the frequency of reports in the post-marketing period of observation about the development of rhabdomyolysis associated with taking rosuvastatin was higher with the dose of 40 mg.

Creatine phosphokinase determination

The determination of CPK activity should not be performed after intense physical activity or in the presence of other possible causes of increase in its activity, which may lead to misinterpretation of the obtained results. If the baseline CPK activity is significantly elevated, a repeat measurement should be performed after 5-7 days – therapy should not be started if the repeat test confirms the baseline CPK activity (5 times higher than normal).

Before initiating therapy

. Caution should be exercised when prescribing Rosart, as with other HMG-CoA reductase inhibitors, in patients with existing risk factors for myopathy/ rhabdomyolysis (see section Cautions). It is necessary to consider the ratio of the expected benefit of therapy to the potential risk and to conduct clinical monitoring throughout the course of treatment. If baseline CPK activity is significantly elevated (5-fold higher than VGN), treatment should not be initiated with the drug.

At the time of treatment

The patient should be informed of the need to immediately inform the physician if muscle pain, muscle weakness or cramps occur unexpectedly, especially if combined with malaise and fever. In such patients, CPK activity should be determined. Therapy should be discontinued if CPK activity is significantly increased (more than 5 times that of IGN) or if muscle symptoms are severe and cause daily discomfort (even if CPK activity is 5 times that of IGN). If symptoms disappear and CPK activity returns to normal, re prescription of Rosart or other HMG-CoA reductase inhibitors at lower doses with close monitoring of the patient should be considered. Routine monitoring of CPK activity in the absence of symptoms is inappropriate.

There have been very rare cases of immune-mediated necrotizing myopathy with clinical manifestations as persistent proximal muscle weakness and increased serum CPK activity during treatment or discontinuation of statins, including rosuvastatin.

There have been no indications of increased skeletal muscle effects with rosuvastatin and concomitant therapy. However, an increase in myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibrin acid derivatives (including gemfibrozil), cyclosporine, nicotinic acid in lipid-lowering doses >1 g/day, azole antifungals, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when concomitantly taken with some HMG-CoA reductase inhibitors, therefore concomitant use of gemfibrozil and rosuvastatin is not recommended. The ratio of expected benefit to potential risk when co-administering Rosart and fibrates or nicotinic acid at lipid-lowering doses of >1 g/day should be carefully weighed.

The use of the drug Rosart in a dose of 40 mg at the same time as fibrates is contraindicated (see sections Interaction with other medicinal products and Contraindications).

When treating, and especially during dose adjustment of the drug Rosart, the lipid profile should be monitored every 2-4 weeks and the dose of the drug should be changed accordingly, if necessary. Rosart should not be used in patients with acute and severe symptoms of myopathy or with the presence of risk factors predisposing to the development of renal dysfunction and secondary rhabdomyolysis (e.g. sepsis, arterial hypotension, extensive surgery, trauma, severe metabolic disorders, marked endocrine and electrolyte balance disorders, uncontrolled convulsions).

Influence on liver function

Like other HMG-CoA reductase inhibitors, rosuvastatin should be used with caution in patients who abuse alcohol and/or have a history of liver disease. It is recommended to determine the liver function parameters before the start of therapy and 3 months after the start of therapy. Administration of Rosart should be discontinued or the dose of the drug should be reduced if the serum level of “hepatic” transaminases exceeds 3 times the BHN.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, therapy for the underlying disease should be performed prior to starting treatment with Rosart. In the post-marketing follow-up of rosuvastatin, the incidence of reports of serious liver function abnormalities (manifested primarily by increased hepatic transaminase activity) was higher with the 40 mg dose.

Ethnic groups

In pharmacokinetic studies in patients of mongoloid race compared to Caucasoid race an increase in systemic concentration of rosuvastatin was noted (see section Method of administration). See Term of Use and Dosage and Pharmacokinetics).

HIV protease inhibitors

The co-administration of rosuvastatin and the combination of various HIV protease inhibitors with ritonavir has increased the systemic concentration of rosuvastatin. The decrease in blood lipid concentrations should be carefully evaluated, and the possible increase in plasma rosuvastatin at the start of treatment and during dose escalation of Rosart in patients with HIV taking HIV-protease inhibitors should be taken into account. Concomitant administration of HIV protease inhibitors is not recommended without adjusting the dose of rosuvastatin (see section Method of administration and dosage and Interaction with other medicinal products).

Interstitial lung disease

In the use of some HMG-CoA reductase inhibitors, especially for long periods of time, sporadic cases of interstitial lung disease have been reported. Manifestations of the disease may include dyspnea, non-productive cough and worsening of general well-being (weakness, weight loss and fever). If interstitial lung disease is suspected, therapy with HMG-CoA reductase inhibitors should be discontinued.

Diabetes mellitus IItype

. Some evidence supports that HMG-CoA reductase inhibitors increase blood glucose concentrations and increase the likelihood of developing type II diabetes in some patients. However, this risk is outweighed by the ability of HMG-CoA reductase inhibitors to reduce the risk of vascular complications, so this fact is not a reason to discontinue treatment with rosuvastatin. Clinical follow-up and blood biochemical analysis according to national standards should be established in patients at risk of hyperglycemia (blood glucose concentration 5.6-6.9 mmol/l, body mass index >30 kg/m2, triglyceridemia, arterial hypertension). One study of rosuvastatin reported an overall incidence of diabetes mellitus: 2.8% in the rosuvastatin group and 2.3% in the placebo group mainly in patients with a fasting glucose of 5.6 to 6.9 mmol/L.

Lactose intolerance

Patients with lactose intolerance, lactase deficiency and glucose-galactose malabsorption should not take Rosart because it contains lactose monohydrate.

Influence on the ability to drive and operate vehicles

There have been no studies on the effect of rosuvastatin on the ability to drive and operate vehicles. Patients should be careful when driving vehicles and engaging in potentially dangerous activities, as dizziness may occur during therapy.

Synopsis

5 mg tablets

Circular, biconvex, film-coated white tablets with “ST 1” engraved on one side.

Tablets 10 mg

Circular, biconvex, film-coated, pink tablets with “ST 2” engraved on one side of the tablet.

Tablets 20 mg

Circular, biconvex, film-coated, pink tablets with “ST 3” engraved on one side of the tablet.

Tablets 40 mg

Oval, biconvex pink film-coated tablets with “ST 4” engraved on one side of the tablet.

Contraindications

Contraindications for Rosart in daily doses of 5, 10 and 20 mg:

Side effects

According to data from clinical studies of rosuvastatin, as well as data from its post-marketing use, the following adverse reactions have been observed in patients.

The incidence of adverse reactions is given according to the following classification: very common (³1/10); common (³1/100, < 1/10); infrequent (³1/1000, < 1/100); rare (³1/10000, < 1/1,000); very rare (< 1/10000); frequency unknown (cannot be determined based on available data).

Blood and lymphatic system disorders: frequently, thrombocytopenia.

Disorders of the immune system: rarely – hypersensitivity reactions, including angioedema.

Disorders with the endocrine system: often – diabetes mellitus1.

Mental disorders:frequency unknown – depression.

Nervous system disorders: frequent – headache, dizziness, asthenic syndrome; very rare – polyneuropathy, memory impairment; frequency unknown – peripheral neuropathy, sleep disorders, including insomnia and nightmares.

Disorders with the respiratory system, chest and mediastinum organs: frequency unknown – cough, shortness of breath.

Gastrointestinal tract disorders: frequently – constipation, nausea, abdominal pain; rarely – pancreatitis; frequency unknown – diarrhea.

Liver and biliary tract disorders: rarely – increased activity of “liver” transaminases; very rarely – hepatitis, jaundice;

Disorders with the skin and subcutaneous tissue: infrequent – skin itching, rash, urticaria; frequency unknown – Stevens-Johnson syndrome.

Muscular and connective tissue disorders: frequent – myalgia; rare – myopathy (including myositis), rhabdomyolysis, lupus-like syndrome, muscle rupture; very rare – arthralgia; frequency unknown – immune-mediated necrotizing myopathy; tendon lesions, sometimes with ruptures,

Renal and urinary tract disorders: very rare – hematuria.

Disorders with the genital and mammary glands:very rarely – gynecomastia.

General disorders and disorders at the site of administration:often – asthenic syndrome; frequency unknown – peripheral edema.

1 Frequency depends on the presence of risk factors (fasting blood glucose concentration >5.6 mmol/l, body mass index >30 kg/m2, elevated TG concentration, history of arterial hypertension).

As with other HMG-CoA reductase inhibitors, the incidence of adverse reactions is dose-dependent; adverse effects are usually mild and go away on their own.

Influence on renal function

In patients receiving rosuvastatin, urinalysis with test strips revealed proteinuria, predominantly tubular. Changes in the amount of protein in the urine (from no or trace amounts to ++ or greater) were observed in less than 1% of patients receiving 10-20 mg rosuvastatin and in approximately 3% of patients receiving 40 mg rosuvastatin. Slight changes in urinary protein (from no or trace amounts to +) have been observed with the 20 mg dose. In most cases proteinuria decreases or disappears during therapy and does not indicate the occurrence of acute or progression of existing renal disease.

Hematuria has been observed in patients receiving rosuvastatin, and the available data have shown a low incidence of this adverse reaction.

Effects on the musculoskeletal system

. With all doses of rosuvastatin and especially with doses greater than 20 mg, the development of myalgia, myopathy, including myositis, and, rarely, rhabdomyolysis with or without the development of acute renal failure have been reported.

A dose-dependent increase in creatine phosphokinase (CPK) activity has been observed while taking rosuvastatin. In most cases it was insignificant, asymptomatic and temporary. In case of an increase in CPK activity (more than 5 times that of IGN), therapy should be suspended (see section Special indications).

Influence on liver function

In a small number of patients with rosuvastatin there is a dose-dependent increase in hepatic transaminase activity. In most cases it is small, asymptomatic and temporary.

When using some HMG-CoA reductase inhibitors sexual dysfunction has been observed, single cases of interstitial lung disease have been reported (see section Special indications).

The incidence of reports of rhabdomyolysis, serious renal and hepatic dysfunction (manifested mainly by increased “hepatic” transaminase activity) is higher with a dose of rosuvastatin 40 mg.

Overdose

Pregnancy use

The drug Rosart is contraindicated during pregnancy and lactation.

The use of Rosart in women of childbearing age is possible only if reliable contraceptive methods are used and if the patient is informed about the possible risks of the treatment for the fetus.

Because cholesterol and cholesterol-synthesized substances are important to fetal development, the potential risk of HMG-CoA reductase inhibition exceeds the benefits of using the drug during pregnancy. If a pregnancy is diagnosed during therapy with Rosart, the drug should be stopped immediately and patients should be warned of the potential risk to the fetus.

There are no data on excretion of rosuvastatin with breast milk; therefore, if the drug must be used during lactation, given the possibility of adverse events in breastfed children, the question of stopping breastfeeding should be considered.

Similarities