Suvardio - instructions for use, dose, side effects, contraindications

1 tablet 5 mg contains: active substance: rosuvastatin calcium in terms of rosuvastatin - 5,000 mg; Excipients: lactose anhydrous - 58.690 mg; silicon dioxide colloidal anhydrous - 0.330 mg; cellulose microcrystalline, silicate - 27,500 mg; starch corn dry - 16,500 mg; talc - 1,100 mg; sodium stearyl fumarate - 0.880 mg; tablet shell: hypromellose-2910 - 1,860 mg; Mannitol - 0.150 mg; macrogol 6000 - 0.090 mg; titanium dioxide - 0.645 mg; iron (III) oxide, yellow - 0.056 mg; iron (III) oxide, red - 0.019 mg; talc - 0.180 mg; talc (polishing agent)² 0.057 mg.

1 tablet of 10 mg contains: active substance: rosuvastatin calcium in terms of rosuvastatin - 10,000 mg; Excipients: lactose anhydrous - 53.690 mg; silicon dioxide colloidal anhydrous - 0.330 mg; cellulose microcrystalline, silicate - 27,500 mg; starch corn dry - 16,500 mg; talc - 1,100 mg; sodium stearyl fumarate - 0.880 mg; tablet shell: hypromellose-2910 - 1,860 mg; Mannitol - 0.150 mg; macrogol 6000 - 0.090 mg; titanium dioxide - 0.420 mg; iron (III) oxide, yellow - 0.225 mg; iron (III) oxide, red - 0.075 mg; talc - 0.180 mg; talc (polishing agent)² 0.057 mg.

1 tablet of 20 mg contains: active substance: rosuvastatin calcium in terms of rosuvastatin - 20,000 mg; Excipients: lactose anhydrous - 107,380 mg; silicon dioxide colloidal anhydrous - 0.660 mg; cellulose microcrystalline, silicate - 55,000 mg; corn starch dry - 33,000 mg; talc - 2,200 mg; sodium stearyl fumarate - 1.760 mg; tablet shell: hypromellose-2910 - 3,720 mg; mannitol - 0.300 mg; macrogol 6000 - 0.180 mg; titanium dioxide - 0.840 mg; iron (III) oxide, yellow - 0.450 mg; iron (III) oxide, red - 0.150 mg; talc - 0.360 mg; talc (polishing agent)² - 0.113 mg.

1 tablet of 40 mg contains: active substance: rosuvastatin calcium in terms of rosuvastatin - 40,000 mg; Excipients: lactose anhydrous - 214.760 mg; silicon dioxide colloidal anhydrous - 1,320 mg; cellulose microcrystalline, silicified - 1 10,000 mg; starch corn dry - 66,000 mg; talc - 4,400 mg; sodium stearyl fumarate - 3.520 mg; tablet shell: hypromellose-2910 - 7.440 mg; Mannitol - 0.600 mg; macrogol 6000 - 0.360 mg; titanium dioxide - 1,680 mg; iron (III) oxide, yellow - 0.900 mg; iron (III) oxide, red - 0.300 mg; talc - 0.720 mg; talc (polishing agent)² - 0.226 mg.

²- Used to polish the tablet, the total amount is not included.

Description:

Tablets 5 mg: round biconvex tablets, film-coated, light brown with engraving "RSV 5 "on one side.

Tablets 10 mg: round biconvex tablets, film-coated, brown with engraving "RSV 10 "on one side.

Tablets 20 mg: round biconvex tablets, film-coated, brown with engraving "RSV 20 "on one side.

Tablets 40 mg: round biconvex tablets, film-coated, brown with engraving "RSV 40 "on one side.

Pharmacotherapeutic group:lipid-lowering agent of HMG-CoA reductase inhibitor.

ATX: & nbsp

C.10.A.A Inhibitors of HMG-CoA reductase

C.10.A.A.07 Rosuvastatin

Pharmacodynamics:

Rosuvastatin is a selective, competitive inhibitor of HMG-CoA reductase - enzyme, transforming

3-hydroxy-3-methylglutarylcoenzyme A in mevalonate, the precursor of cholesterol. Rosuvastatin acts on the liver, where the synthesis of cholesterol (Cholesterol) and catabolism of low-density lipoproteins (LDL). Rosuvastatin increases the number of LDL receptors on the surface of hepatocytes that increase the uptake and catabolism of LDL, and inhibits the synthesis of very low-density lipoprotein (LLDPE) proteins, thereby reducing the amount of LDL and VLDL.

Rosuvastatin reduces the concentration of low density cholesteryl lipoprotein (LDL-C), total cholesterol, triglycerides (TG), increases the concentration of high-density cholesterol (HDL-C), and also reduces the concentration of apolipoprotein B (ApoV), XC-nonLH1VP, -LVALP, T-VLDL and increases the concentration of apolipoprotein

A-1 (ApoA-1) (see Table 1), reduces the ratio of LDL-C-LH1VP-cholesterol, total cholesterol / cholesterol-HDL cholesterol and non-HDL-C-HDL cholesterol and ratio

АпоВ / АпоА-1. After the beginning of therapy with rosuvastatin, the therapeutic effect appears within one week, after 2 weeks of treatment it reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved by week 4 and is maintained with regular intake of the drug.

Table 1. The dependence of the response to treatment on the dose of rosuvastatin in patients with primary

hypercholesterolemia (types IIa and IIb according to Fredrickson) (the average adjusted percentage change relative to the initial concentration)

Dose, mg	Amount patients	LDL cholesterol	General HS	HS- lpvp	TG	Cholesterol-free HDL	APOP	AnoA1
Placebo	13	-7	-5	3	-3	-7	-3	0
5	17	-45	-33	13	-35	-44	-38	4
10	17	-52	-36	14	-10	-48	-42	4
20	17	-55	-40	8	-23	-51	-46	5
40	18	-63	-46	10	-28	-60	-54	0

Clinical efficacy

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

In 80% of patients with hypercholesterolemia IIa and IIb type (according to the average initial concentration of LDL-C, about 4.8 mmol / L), when using rosuvastatin at a dose of 10 mg, the concentration of LDL-C is less than 3 mmol / l.

In patients with heterozygous familial hypercholesterolemia who took rosuvastatin in doses from 20 to 80 mg according to the scheme of forced titration of doses, positive dynamics of indices of the lipid profile was noted. After titrating the daily dose to 40 mg per day (12 weeks of therapy), the concentration of LDL-C has decreased by 53%. In 33% of patients, the concentration of LDL-C was lower than 3 mmol / l. In patients with homozygous familial hypercholesterolemia who took rosuvastatin in doses of 20 and 40 mg, the average decrease in the concentration of LDL-C was 22%.

The additive effect is noted in combination with fenofibrate for the concentration of TG and with nicotinic acid (more than 1 g per day) for the concentration of cholesterol-HDL.

In patients with a low risk of developing coronary heart disease (CHD) (the risk of the Framingham scale is less than 10% over a period of more than 10 years), with an average LDL cholesterol concentration of 4.0 mmol / L (154.5 mg / dL) and subclinical atherosclerosis , which was assessed by the thickness of the intima-media complex of carotid arteries (TKIM), rosuvastatin in a dose of 40 mg / day significantly slowed the progression of the maximum TKIM for 12 segments of the carotid artery compared with placebo at a rate of 0.0145 mm / year (95% confidence interval (CI): -0.0196 to -0.0093, with p <0.0001). A dose of 40 mg should be given only to patients with severe hypercholesterolemia and a high risk of developing cardiovascular diseases.

Pharmacokinetics:

Absorption

The maximum concentration (C_max) rosuvastatin in the blood plasma is reached approximately 5 hours after ingestion. Absolute bioavailability is ~ 20%.

Distribution

Rosuvastatin is metabolized primarily by the liver, which is the main site for the synthesis of cholesterol and the metabolism of LDL-C. The volume of distribution of rosuvastatin is approximately 134 liters. About 90% of rosuvastatin binds to blood plasma proteins, mainly albumin.

Metabolism

Biotransformation is subject to a limited amount of rosuvastatin (approximately 10%).

The metabolism of rosuvastatin is to a small extent connected with the isoenzymes of the cytochrome P450 system. Isozyme CYP2C9 is the main isoenzyme involved in the metabolism of rosuvastatin, while isozymes CYP2C19, CYP3A4 and CYP2D6 are less involved in metabolism. The main revealed metabolites of rosuvastatin are N-dismethyl-rosuvastatin and lactone metabolites.

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

Excretion

Approximately 90% of the administered dose of rosuvastatin is excreted unchanged through the intestine (including absorbed and absorbed rosuvastatin), the rest is excreted by the kidneys. In an unchanged form, about 5% of the administered dose is excreted by the kidneys. The half-life (T_1/2) is 19 hours, 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 inhibitors of HMG-CoA reductase, the membrane transfer of cholesterol through membranes is involved in the process of "hepatic" uptake of rosuvastatin. This carrier plays an important role in the excretion of rosuvastatin by the liver.

Linearity

The systemic exposure of rosuvastatin increases in proportion to the dose. After repeated daily administration of the drug, there is no change in the pharmacokinetic parameters.

Genetic polymorphism

Inhibitors of GMC-CoA reductase, including rosuvastatin, bind to transport proteins OATP1B1 (the polypeptide of organic anion transport, involved in the capture of statins by hepatocytes) and BCRP (efflux conveyor). In carriers of genotypes SLC01B1 (OATP1B1) p.521N and ABCG2 (BCRP) p.421AA there was an increase in exposure (AUC - the area under the "concentration - time" curve) of rosuvastatin 1.6 and 2.4 times, respectively, compared with the carriers of genotypes SLC01Blc.521TT and

ABCG2 p.421AA.

Special populations of patients

Age and gender

Age and sex do not have a clinically significant effect on the pharmacokinetic parameters of rosuvastatin.

Ethnic groups

Pharmacological studies showed approximately a twofold increase in the median AUC and C_m_Oh rosuvastatin in patients of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with those of the Caucasoid race; Hindu patients showed an increase in the median AUC and C_m_Oh approximately in 1,3 times. At the same time, the analysis of the pharmacokinetics indices for the whole study population did not reveal clinically significant differences in the pharmacokinetics of the drug among representatives of the Caucasoid and Negroid races.

Renal insufficiency

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

In patients with varying degrees of hepatic insufficiency with a score of 7 or lower on the Child-Pugh scale, there was no increase in T_1/2 rosuvastatin. However, in 2 patients with scores of 8 and 9 but on the Child-Pugh scale, an elongation of T_1/2, approximately 2 times higher than that for patients with lower scores Child-Pugh. The experience with rosuvastatin in patients with a score above 9 on the Child-Pugh scale is not available.

Indications:

for a daily dose of 5 mg, 10 mg and 20 mg:

increased sensitivity to rosuvastatin or any of the components of the drug;

- liver diseases in the active phase, including persistent increase in the activity of "liver" transaminases, as well as any increase in the activity of "hepatic" transaminases in the serum of more than

3 times compared with the upper limit of the norm (VGN);

- severe renal dysfunction (CC less than 30 ml / min);

- myopathy;

- simultaneous administration of cyclosporine;

- pregnancy, the period of breastfeeding;

- use in patients predisposed to the development of myotoxic complications;

- deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome (the preparation contains lactose);

- age to 18 years (efficacy and safety not established).

- for a daily dose of 40 mg:

- increased sensitivity to rosuvastatin or any of the components of the drug;

3 times compared with the upper limit of the norm (VGN);

- presence of risk factors for myopathy / rhabdomyolysis:

- renal failure of moderate severity (CK <60 ml / min);

- hypothyroidism;

- myopathies in the anamnesis, including hereditary;

- myotoxicity on the background of taking other inhibitors of HMG-CoA reductase or fibrates in anamnesis;

- excessive use of alcohol;

- conditions that may lead to an increase in the plasma concentration of rosuvastatin;

- simultaneous reception of fibrates;

- use in patients of the Mongoloid race;

- simultaneous administration of cyclosporine;

- pregnancy, the period of breastfeeding;

- use in patients predisposed to the development of myotoxic complications;

- deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome (the preparation contains lactose);

- age under 18 years (efficiency and safety not established).

Contraindications:

for a daily dose of 5 mg, 10 mg and 20 mg:

- increased sensitivity to rosuvastatin or any of the components of the drug;

3 times compared with the upper limit of the norm (VGN);

- severe renal dysfunction (CC less than 30 ml / min);

- myopathy;

- simultaneous administration of cyclosporine;

- pregnancy, the period of breastfeeding;

- use in patients predisposed to the development of myotoxic complications;

- deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome (the preparation contains lactose);

- age to 18 years (efficacy and safety not established).

- for a daily dose of 40 mg:

- increased sensitivity to rosuvastatin or any of the components of the drug;

3 times compared with the upper limit of the norm (VGN);

- presence of risk factors for myopathy / rhabdomyolysis:

- renal failure of moderate severity (CK <60 ml / min);

- hypothyroidism;

- myopathies in the anamnesis, including hereditary;

- myotoxicity on the background of taking other inhibitors of HMG-CoA reductase or fibrates in anamnesis;

- excessive use of alcohol;

- conditions that can lead to an increase in the plasma concentration of rosuvastatin;

- simultaneous reception of fibrates;

- use in patients of the Mongoloid race;

- simultaneous administration of cyclosporine;

- pregnancy, the period of breastfeeding;

- use in patients predisposed to the development of myotoxic complications;

- deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome (the preparation contains lactose);

- age to 18 years (efficacy and safety not established).

Carefully:

For a daily dose of 5 mg, 10 mg and 20 mg: presence of risk of development of myopathy / rhabdomyolysis - renal failure, hypothyroidism; personal or family history of hereditary muscle diseases and a previous history of muscle toxicity with the use of other inhibitors of HMG-CoA reductase (statins) or fibrates; excessive use of alcohol; state,at which there was an increase in the plasma concentration of rosuvastatin; age over 65; high risk of diabetes; liver disease in history; sepsis; arterial hypotension; extensive surgical interventions; injuries; severe metabolic, endocrine or water-electrolyte disorders; uncontrolled epilepsy; race (Mongoloid race); simultaneous reception of fibrates.

For a daily dose of 40 mg: presence of myopathy / rhabdomyolysis risk - mild renal insufficiency (QC more than 60 ml / min), age over 65; high risk of diabetes; liver disease in history; sepsis; arterial hypotension; extensive surgical interventions; injuries; severe metabolic, endocrine or water-electrolyte disorders, uncontrolled epilepsy.

Pregnancy and lactation:

The drug Suvardio® is contraindicated for use during pregnancy and during breastfeeding. Women of reproductive age should use reliable and adequate contraception. Since cholesterol and the products of cholesterol biosynthesis are of great importance for fetal development,the potential risk of inhibiting HMG-CoA reductase exceeds the benefit of its use in pregnancy. If pregnancy is diagnosed, the preparation of Suvardio® should be discontinued immediately.

Data on the allocation of rosuvastatin with breast milk are absent. If it is necessary to prescribe the drug Suvardio® during lactation, it is necessary to solve the problem of stopping breastfeeding.

Dosing and Administration:

Inside. At any time of the day, regardless of food intake. The tablet can not be chewed, chopped, swallowed whole, washed down with water. Before starting therapy with Suvardio®, the patient should begin to follow the standard hypocholesterolemic diet and continue to observe it throughout the treatment period.

The dose of Suvardio® is selected individually taking into account the target values of cholesterol concentration and individual therapeutic response to the therapy.

Recommended initial dose of the Suvardio® preparation is 5 mg or 10 mg once a day for both patients who did not previously take statins and for patients who were switched to receiving this drug after treatment with other HMG-CoA reductase inhibitors.

When choosing the initial dose should be guided by the concentration of cholesterol and the possible risk of cardiovascular complications in this patient, as well as the potential risk of side effects.

If necessary, after 4 weeks, you can adjust the dose of the drug. In connection with the possible development of side effects when taking a dose of 40 mg compared with lower doses of the drug, the final titration to a maximum dose of 40 mg should be performed only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia) in whom a target concentration of cholesterol was not achieved when taking a dose of 20 mg and which will be under medical supervision. When appointing a dose of 40 mg, a thorough observation of the doctor is recommended.

Do not administer a dose of 40 mg to patients who have not previously consulted a doctor.

Elderly patients

For patients over 65 years, the recommended initial dose of Suvardio® is 5 mg. In other cases, dose adjustments due to age are not required.

Patients with renal insufficiency

In patients with mild or moderate renal insufficiency, dosage correction of the Suvardio® preparation is not required. The recommended initial dose of the drug is 5 mg for patients with moderate-grade renal failure (CC less than 60 mL / min). The use of Suvardio® in any doses is contraindicated in patients with severe renal insufficiency (QC less than 30 ml / min) (see section "Contraindications").

Patients with renal insufficiency of moderate severity are contraindicated administration of the drug in a dose of 40 mg (see the section "Contraindications").

Patients with hepatic insufficiency

An increase in the systemic concentration of rosuvastatin in patients with a Child-Pugh score of 7 or lower was not detected. However, an increase in systemic rosuvastatin concentrations was observed in patients with Child-Pugh score 8 and 9. These patients should be monitored for liver function against rosuvastatin therapy. Data on the administration of rosuvastatin in patients with a Child-Pugh score above 9 are not available. Patients with liver disease in the active phase rosuvastatin contraindicated (seesection "Contraindications").

Special Populations

Ethnic groups

In patients of the Mongoloid race, an increase in the systemic concentration of rosuvastatin in the blood plasma is possible. The recommended initial dose of Suvardio® in patients of the Mongoloid race is 5 mg. The use of the drug in a dose of 40 mg to such patients is contraindicated (see section "Contraindications").

Patients predisposing to development of myopathy

The recommended initial dose of Suvardio® for patients with predisposition to the development of myopathy is 5 mg. The use of the drug in a dose of 40 mg to such patients is contraindicated (see section "Contraindications").

Genetic polymorphism

In carriers of genotypes SLC01B1 (OATP1B1) p.521N and ABCG2 (BCRP) p.421AA there was an increase in exposure (AUC) rosuvastatin 1.6 and 2.4 times, respectively, compared with carriers of genotypes SLC01B1from.521TT and ABCG2 p.421AA. For carriers of genotypes с.521СС or с.421АА the recommended maximum dose of the drug Suvardio® is 20 mg once a day (see Section "Pharmacokinetics").

Accompanying teranand I

Rosuvastatin binds to various transport proteins (in particular, to OATP1B1 and BCRP). With the simultaneous use of the drug Suvardio® with medicines (such as ciclosporin, some human immunodeficiency virus (HIV) protease inhibitors, including a combination of ritonavir with atazanavir, lopinavir and / or tipranavir), which increase the concentration of rosuvastatin in blood plasma through interaction with transport proteins, may increase the risk of myopathy (including rhabdomyolysis) (see section "Interactions with other drugs", it is necessary to familiarize yourself with the instructions for the use of these drugs before prescribing the drug Suvardio®). In such cases, the possibility of using alternative therapy or temporary discontinuation of Suvardio® should be assessed. If it is necessary to use the above drugs, the relationship between the benefit and the risk of concomitant therapy with Suvardio® should be assessed and the possibility of reducing its dose should be considered.

Side effects:

According to the World Health Organization (WHO), adverse reactions are classified according to their frequency of development as follows: very often (>1/10), often (>1/100, <1/10), infrequently (>1/1000, <1/100), rarely (>1/10000, <1/1000) and very rarely (<1/10000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

Violations of the blood and lymphatic system frequency unknown: thrombocytopenia.

Immune system disorders

rarely: hypersensitivity reactions, including angioedema.

Disorders from the endocrine system

often: diabetes mellitus type 2.

Violations from the neutral nervous system often: headache, dizziness;

rarely: polyneuropathy, memory loss. Disturbances from the respiratory system frequency unknown: cough, shortness of breath.

Disorders from the digestive system often: constipation, nausea, pain in the abdomen; rarely: pancreatitis;

frequency unknown: diarrhea.

Disturbances from the skin infrequently: skin itching, rash, hives;

frequency is unknown: Stevens-Johnson syndrome. Laboratory indicators

Increase in activity of creatine phosphokinase (CK), glucose concentration, glycosylated hemoglobin, bilirubin in blood plasma, activity of gamma-glutamyltranspeptidase, alkaline phosphatase, thyroid dysfunction.

Other

often: asthenic syndrome, gynecomastia, peripheral edema.

Disorders from the urinary system

rarely: hematuria.

When taking rosuvastatin, proteinuria can be observed. Changes in the protein content in the urine (from absence to the presence of trace amounts to the level of ++ and higher) are observed in less than 1% of patients taking rosuvastatin in a dose of 10 mg and 20 mg, and about 3% taking the drug at a dose of 40 mg. A slight change in the amount of protein in the urine, expressed in a change from zero level or the presence of traces to the level of +, was observed when taking the drug at a dose of 20 mg. In most cases, proteinuria decreased and passed independently during the treatment. When analyzing the data of clinical studies, there is no causal relationship between proteinuria and acute or progressive kidney disease.

Disorders from the musculoskeletal system and connective tissue

often: myalgia;

rarely: Myopathy (including myositis), rhabdomyolysis;

rarely: arthralgia;

frequency is unknown: immuno-mediated necrotizing myopathy. Disturbances from the liver and bile ducts

rarely: increased activity of "liver" transaminases;

rarely: jaundice, hepatitis.

With the use of some statins reported on such side effects as: depression, sleep disturbance, including insomnia and nightmares dreams, sexual dysfunction.

Overdose:There is no specific treatment for an overdose of rosuvastatin. In case of an overdose, it is recommended to carry out symptomatic treatment and measures aimed at maintaining the function of vital organs and systems. It is necessary to monitor the liver function and the activity of CK. It is unlikely that hemodialysis will be effective.

Interaction:

With simultaneous application of rosuvastatin and cyclosporine AUC of rosuvastatin was an average of 7 times higher than that seen in healthy volunteers. Joint use of these drugs leads to an increase in the concentration of rosuvastatin in blood plasma by 11 times, while the plasma concentration of cyclosporine does not change (see the section "Contraindications").

With the use of other statins, reports of cases of rhabdomyolysis with simultaneous application of rosuvastatin and fusidic acid have been received, monitoring of patients' condition is necessary, and, if necessary, temporary interruption of rosuvastatin administration.

As with other HMG-CoA reductase inhibitors, initiation of rosuvastatin therapy or an increase in the dose of the drug in patients receiving concomitantly antagonists of vitamin K (eg, warfarin or other coumarin anticoagulants) can lead to an increase in the international normalized ratio (MHO). Cancellation or reduction of the dose of rosuvastatin may cause a decrease in MNO. In such cases, monitoring MHO.

The simultaneous use of rosuvastatin and gemfibrozil and other means that reduce the concentration of lipids, leads to an increase in C_m_Oh and AUC rosuvastatin in 2 times.

Table 2. The influence of concomitant therapy on the exposure of rosuvastatin

(AUC, data are listed in descending order)

Complementary therapy regimen		Mode of taking rosuvastatin	Change AUC rosuvastatin
Cyclosporine 75-200 mg 2 times a day, 6 months		10 mg once a day, 10 days	An increase of 7.1 times
Atazanavir 300 mg / ritonavir 100 mg once a day, 8 days		10 mg once	Increase 3.1-fold
Lopinavir 400 mg / ritonavir 100 mg twice daily, 17 days		20 mg once a day, 7 days	An increase of 2.1 times
Hemifibrozil 600 mg 2 times a day, 7 days		80 mg once	The increase in 1, 9 times
Eltrombopag 75 mg once a day, 10 days		10 mg once	Increase 1.6 times
Darunavir 600 mg / ritonavir 100 mg twice daily, 7 days		10 mg once a day, 7 days	Increase by 1.5 times
Tipranavir 500 mg / ritonavir 200 mg twice daily, 11 days		10 mg once	Increase by 1.4 times
Dronedarop 400 mg twice daily		No data	Increase by 1.4 times
Itraconazole 200 mg once daily, 5 foxes	10 mg or 80 mg once		Increase by 1.4 times
Ezetimibe 10 mg once a day, 14 days	10 mg once a day, 14 days		Increase by 1.2 times
Fosaprenavir 700 mg / ritoavir 100 mg twice daily, 8 days	10 mg once		Without changes
Aleglitazar 0.3 mg, 7 days	40 mg, 7 days		Without changes
Silymarin 140 mg 3 times a day, 5 days	10 mg once		Without changes
Fenofibrate 67 mg 3 times a day, 7 days	10 mg, 7 days		Without changes
Rifampicin 450 mg once a day, 7 days	20 mg once		Without changes
Ketoconazole 200 mg 2 times a day, 7 days	80 mg once		Without changes
Fluconazole 200 mg once a day, 11 days	80 mg once		Without changes
Erythromycin 500 mg 4 times a day, 7 days	80 mg once		Decrease by 28%
Baikalian 50 mg 3 times a day, 14 days	20 mg once		Decrease by 47%

Based on the data on the specific interaction, no pharmacokinetically significant interaction with fenofibrate, possibly pharmacodynamic interaction.

Gemfibrozil, fenofibrate, other fibrates and a nicotinic acid in lipid-lowering doses (1 g or more per day) with simultaneous use with HMG-CoA reductase inhibitors increased the risk of myopathy, possibly due to the fact that they can cause myopathy and when used in monotherapy. Simultaneous application of 40 mg rosuvastatin and fibrates is contraindicated. With the simultaneous use of the drug with gemfibrozil and other lipid-lowering agents, the initial dose of rosuvastatin is 5 mg. With simultaneous application of rosuvastatin and ezetimibe there is no change AUC or with_m_Oh both preparations. However, it is impossible to exclude the possibility of pharmacodynamic interaction between rosuvastatin and ezetimibe, which can cause undesirable phenomena. Despite the fact that the exact mechanism of interaction is unknown, simultaneous application of rosuvastatin with protease inhibitors can lead to an elongation T_1/2 rosuvastatin. In a pharmacokinetic study with simultaneous administration of 20 mg rosuvastatin and a combined preparation containing two protease inhibitors (400 mg lopinavir / 100 mg ritonavir), healthy volunteers showed a 2-fold increase AUC(o-24) and 5 times the C_max rosuvastatin, respectively. Therefore, simultaneously appoint rosuvastatin and protease inhibitors in the treatment of patients with the human immunodeficiency virus (HIV) are not recommended.

The simultaneous use of rosuvastatin and antacids in suspensions containing aluminum or magnesium hydroxide leads to a decrease in the plasma concentration of rosuvastatin by approximately 50%. This effect is less pronounced if antacids are administered 2 hours after rosuvastatin administration. The clinical significance of such an interaction is not established.

The simultaneous use of rosuvastatin and erythromycin leads to a decrease AUC_(0-24) rosuvastatin by 20% and C_m_Oh rosuvastatin by 30%. Such interaction can be caused by increased intestinal motility caused by the administration of erythromycin.

The simultaneous use of rosuvastatin and oral contraceptives increases the AUC ethinylestradiol and AUC norgestrel by 26% and 34%, respectively. Such an increase in plasma concentrations should be considered when choosing a dose of oral contraceptives.

Pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement therapy There are no, therefore, it is impossible to exclude a similar effect when applying this combination. However, this combination was widely used by women during clinical trials and was well tolerated.

No clinically significant interaction is expected with simultaneous application of rosuvastatin and digoxin.

Research results in vivo and in vitro showed that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. Besides, rosuvastatin is a weak substrate for these isoenzymes. There was no clinically significant interaction between rosuvastatin and fluconazole (inhibitor of isoenzymes CYP2C9 and CYP3A4) or ketocobalase (inhibitor of isoenzymes CYP2A6 and CYP3A4). The combined use of rosuvastatin and itraconazole (inhibitor of isoenzyme CYP3A4) increases the AUC rosuvastatin by 28% (clinically not significant). Therefore, any interaction of drugs associated with the metabolism of cytochrome P450 is not expected.

Special instructions:Proteinuria (determined using test strips), mainly of tubular origin,was noted in patients receiving high doses of rosuvastatin, in particular 40 mg, but in most cases it was periodic or short-term. It is shown that such proteinuria does not mean the emergence of acute or progressive disease of the existing kidney disease. The frequency of severe renal dysfunction increases with taking 40 mg rosuvastatin. It is recommended to monitor the parameters of kidney function during rosuvastatin therapy. When using Suvardio ® in all doses and, in particular, when taking the drug at a dose exceeding 20 mg, myalgia, myopathy and, in rare cases, rhabdomyolysis were detected. Very rarely there was rhabdomyolysis with simultaneous administration of ezetimibe and inhibitors of HMG-CoA reductase.

In this case, the pharmacological interaction of the drugs can not be ruled out, therefore, jointly the preparation of Suvardio® and ezetimibe should be used with caution.

The incidence of rhabdomyolysis with the intake of 40 mg of Suvardio® is increasing.

Determination of CKK activity should not be performed after intensive physical exertion or in the presence of other possible causes of increased activity of CK, which may lead to incorrect interpretation of the results.In the event that the activity of CKK before the start of therapy is significantly increased (5 times higher than HHV), after 5-7 days, a second measurement should be carried out. lie should start therapy with Suvardio®, if the repeated test confirms the initial activity of CKK (more than 5 times higher than that of HHV).

Rosuvastatin, like other inhibitors of HMG-CoA reductase, should be used with extreme caution in patients with existing risk factors for myopathy / rhabdomyolysis. Such factors include:

- kidney failure;

- hypothyroidism (for a dose of 40 mg);

- myopathy in the history (including hereditary) (for a dose of 40 mg);

- presence in the anamnesis of myotoxicity on the background of taking other inhibitors of HMG-CoA reductase or fibrates (for a dose of 40 mg);

- alcohol abuse (for a dose of 40 mg);

- age over 65;

- conditions, accompanied by an increase in the plasma concentration of rosuvastatin (for a dose of 40 mg);

- simultaneous reception of fibrates (for a dose of 40 mg).

In such patients, the risk-to-benefit ratio of therapy should be assessed and clinical observation performed throughout the course of therapy.

It is recommended that patients be informed of the need to report promptly to the doctor about cases of unexpected muscle pain, muscle weakness or spasms,especially when combined with a malaise or fever!

In such patients, it is necessary to monitor the activity of CK. Treatment should be discontinued if the activity of CK is more than 5 times higher than UGN, or if muscle symptoms are severe and cause daily discomfort throughout the day (even if the activity of CK is 5 times lower than ULN). If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing the drug or prescribing an alternative inhibitor of HMG-CoA reductase in smaller doses with careful monitoring of the patient. Regular monitoring of the activity of CK in patients with no symptoms of rhabdomyolysis is inexpedient.

There were no signs of an increase in undesirable phenomena from the skeletal musculature when taking the Suvardio® preparation and concomitant therapy. However, an increase in the incidence of myositis and myopathy was found in patients taking other HMG-CoA reductase inhibitors together with fibrin acid derivatives, including gemfibrozil, ciclosporin, nicotinic acid in lipid-dosing doses (more than 1 g / day), azole antifungal agents, protease inhibitors and macrolide antibiotics.Gemfibrozil increases the risk of myopathy when combined with certain HMG-CoA reductase inhibitors. Therefore, simultaneous administration of rosuvastatin and gemfibrozil is not recommended. It is necessary to carefully evaluate the risk-benefit ratio when rosuvastatin is used together with fibrates or nicotinic acid in lipid-lowering doses (more than 1 g / day). Contraindicated simultaneous administration of rosuvastatin in a dose of 40 mg and fibrates. Suvardio's drug should not be given to patients with acute, severe illness, suspected myopathy or possible secondary renal failure (eg, sepsis, hypertension, surgery, trauma, metabolic syndrome, diabetes mellitus, seizures, endocrine disorders, water-electrolyte violations).

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

Like other inhibitors of HMG-CoA reductase, rosuvastatin should be used with extreme caution in patients who abuse alcohol or who have a history of liver disease.

It is recommended to perform the determination of liver function indicators before and after 3 months after the start of treatment. If the activity of "hepatic" transaminases in the serum is 3 times higher than the upper limit of the norm, stop taking the medication or reduce the dose taken. The frequency of pronounced violations of the liver (associated mainly with an increase in the activity of "liver" transaminases), increases with taking 40 mg of the drug. In patients with secondary hypercholesterolemia due to hypothyroidism, nephrotic syndrome, therapy of the underlying disease should be performed prior to the initiation of treatment with rosuvastatin. In the course of pharmacokinetic studies, an increase in the systemic concentration of rosuvastatin among patients of the Mongoloid race was found in comparison with data obtained from representatives of the Caucasoid race.

Simultaneous administration of rosuvastatin with HIV protease inhibitors is not recommended.

With the use of some statins, especially over a long period of time, single cases of interstitial lung disease have been reported. Manifestations of the disease can be shortness of breath, unproductive cough and deterioration in overall health (weakness,weight loss and fever). If suspicion of interstitial lung disease should be stopped by statin therapy. In patients with a glucose concentration of 5.6 to 6.9 mmol / L, drug therapy was associated with an increased risk of developing type 2 diabetes.

Special precautions for the destruction of unused medicinal product

There is no need for special precautions when destroying an unused Suvardio® preparation.

Effect on the ability to drive transp. cf. and fur:Care must be taken when driving vehicles, engaging in potentially hazardous activities requiring increased concentration and speed of psychomotor reactions (risk of dizziness).

Form release / dosage:

Tablets, film-coated 5 mg, 10 mg, 20 mg and 40 mg.

Packaging:

For 7 tablets in Al / Al blister. For 1, 2 or 4 blisters per pack of cardboard along with instructions for use.

Storage conditions:In the original packaging in a dry place at a temperature of no higher than 25 ° C. Keep out of the reach of children!

Shelf life:

2 years.

Do not use the product after the expiry date printed on the package!

Terms of leave from pharmacies:On prescription

Registration number:LP-003023

Date of registration:04.06.2015

Date of cancellation:2020-06-04

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

LEK d.d. Slovenia

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp29.05.2016

Illustrated instructions

Instructions

Suvardio® (Suvardio®)