Romazik 20 mg tablet number 30

Romazik user's manual

Composition

active ingredient: rosuvastatine; 1 coated tablet contains rosuvastatin 5 mg or 10 mg or 20 mg or 40 mg, equivalent to 5.2 mg 10.4 mg, 20.8 mg, 41.6 mg of rosuvastatin calcium;
auxiliary substances: lactose, type 1; lactose, type 2, microcrystalline sodium cellulose; crospovidone type B; silicon colloidal magnesium stearate shell (Opadry II white dye 33G28523, hypromellose, lactose, macrogol, triacetin, titanium dioxide (E 171)).

Dosage form

Film-coated tablets.

Basic physical and chemical properties:

5 mg: round, biconvex tablets, film-coated, white or almost white, embossed "5" on one side;
10 mg: round, biconvex tablets, film-coated, white or almost white, embossed "10" on one side
20 mg: round, biconvex tablets, film-coated, white or almost white, embossed "20" on one side
40 mg oblong, biconvex tablets, film-coated, white or almost white.

Pharmacological group

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

Pharmacological properties

Pharmacodynamics.

Rosuvastatin reduces elevated levels of LDL cholesterol, total cholesterol and triglycerides, and also increases HDL cholesterol (high-density lipoproteins).

The drug also reduces the level of alipoprotein B (ApoB), non-LDL cholesterol, VLDL cholesterol, VLDLP triglycerides and increases the level of apolipoprotein AI (ApoA-I) (see Table).

Rosuvastatin also reduces the ratio of LDL cholesterol / HDL cholesterol, total cholesterol / HDL cholesterol, non-HDL / HDL cholesterol and ApoA / ApoA-I cholesterol.

Table 1.

A dose-response response in patients with primary hypercholesterolemia (type IIa and IIb) (adjusted average percent change versus baseline)

Dose	N	X-LDL	total cholesterol	HDL-C	TG	non-HDL-X	ApoB	ApoA-I
placebo	13	7th	-5	3	3	-7	3	0
5	17th	45	33	13	35	44	38	4
10	17th	52	36	14	10	48	42	4
20	17th	55	40	8	23	51	46	5
40	18	63	46	10	28	60	54	0

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

Pharmacokinetics.

Suction

The maximum concentration of rosuvastatin in blood plasma is reached after 5:00 after oral administration.Bioavailability is approximately 20%.

Distribution

Rosuvastatin is extensively absorbed by the liver, which is the main site for the synthesis of cholesterol and the clearance of LDL cholesterol. The volume distribution of rosuvastatin is approximately 134 liters. About 90% of rosuvastatin binds to blood plasma proteins, mainly with albumin.

Metabolism

Rosuvastatin undergoes limited metabolism (about 10%). In vitro studies of metabolism using human hepatocytes indicate that rosuvastatin is a weak substratum for cytochrome P450 mediated metabolism. CYP2C9 is the main isoenzyme involved, and 2C19, 3A4 and 2D6 are less involved. The main identified metabolites are N-dysmethyl and lactone metabolites. The metabolite of N-dimethyl is about 50% less active than rosuvastatin, and lactone forms are considered clinically inactive. Rozuvastatin accounts for more than 90% of the activity of the HMG CoA inhibitor in circulating blood.

Conclusion

Approximately 90% of the dose of rosuvastatin is excreted unchanged with feces (including absorbed and unabsorbed active substance), and the rest is excreted in the urine.

Approximately 5% is excreted in the urine unchanged. The half-life of the plasma is approximately 19 hours. The elimination half-life is not prolonged with high doses. The average geometric indicator of blood plasma clearance is approximately 50 l / h (coefficient of variation 21.7%). As in the case of other inhibitors of HMG-CoA reductase, the membrane carrier OATP-C participates in the process of hepatic engagement of rosuvastatin. This carrier plays an important role in the hepatic elimination of rosuvastatin.

Linearity

The systemic exposure of rosuvastatin is enhanced proportionally to the dose. After repeated daily use, no changes in pharmacokinetic parameters are observed.

Individual groups

Age and gender

Age and sex do not influence clinically significant pharmacokinetics of rosuvastatin in adults. The pharmacokinetics of rosuvastatin in children and adolescents with heterozygous familial hypercholesterolemia was similar to that of adult volunteers (see "Children" below).

Race

Pharmacokinetic studies show an increase in the average values of AUC and C max in representatives of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with representatives of the European race; in the Asian race, the average values of AUC and C max increase approximately 1.3 times. Population pharmacokinetic analysis indicates the absence of clinically significant differences in the pharmacokinetics between Caucasoid and Negroid races.

Impaired renal function

In a study involving patients with varying degrees of renal dysfunction, with mild and moderate renal disease, no effect was observed on plasma concentrations of rosuvastatin and N-dimethyl metabolite. In patients with severe renal dysfunction (CK <30 ml / min), an increase in plasma concentration by a factor of 3 was observed and an increase in the concentration of N-dimethyl metabolite was 9-fold compared to healthy volunteers. The concentrations of rosuvastatin in blood plasma at equilibrium in patients undergoing hemodialysis were approximately 50% greater than in healthy volunteers.

Impaired liver function

In a study involving patients with varying degrees of liver function disorder at 7 or lower on the Child-Pugh scale, systemic exposure to rosuvastatin was NOT enhanced. However, in 2 patients with indicators 8 and 9 on the Child-Pugh scale, there was an increase in systemic exposure by at least 2-fold compared with patients with low Child-Pugh scores.There is no experience of using the drug in patients with a score above 9 on the Child-Pugh scale.

Children

Pharmacokinetic parameters in children with heterozygous familial hypercholesterolemia at the age of 10 to 17 years have not been fully studied. A small pharmacokinetic study of rosuvastatin (in the form of tablets) in 18 children showed that the exposure of the drug in children is comparable to that of adult patients. In addition, the results indicate no significant deviation from dose-response.

Indications

Treatment of hypercholesterolemia

Adults, adolescents and children over 10 years of age with primary hypercholesterolemia (such as Pa, including heterozygous familial hypercholesterolemia) or mixed dyslipidemia (type IBb) as a supplement to the diet, when diet and other non-medicament means (eg exercise, weight reduction body) is inadequate.

In case of homozygous familial hypercholesterolemia, it is an addition to the diet and other lipid-lowering medications (for example, LDL apheresis) or in cases when such treatment is inappropriate.

Prevention of cardiovascular disorders

Preventing a significant cardiovascular disorder in patients who are estimated to be at high risk for the first case of cardiovascular disorder (see Section "Pharmacological"), in addition to correcting other risk factors.

Contraindications

• Hypersensitivity to rosuvastatin or to any of the excipients of the drug
• liver diseases in the active stage, including a steady increase in the activity of serum transaminases of unknown etiology, as well as an increase in the activity of any serum transaminase more than 3 times higher than the upper limit of the norm (BMD)
• severe renal dysfunction (creatinine clearance <30 mL / min);
• myopathy;
• simultaneous application of cyclosporine;
• the period of pregnancy and lactation, as well as women of reproductive age who do not use contraceptive means.

The drug in a dose of 40 mg is contraindicated in patients with factors contributing to the development of myopathy / rhabdomyolysis. Such factors include:

• mild renal impairment (creatinine clearance <60 mL / min);
• hypothyroidism
• hereditary diseases of the muscular system in a personal or family anamnesis
• in the anamnesis - myotoxicity when using another inhibitor of HMG CoA reductase or fibrates;
• alcohol abuse;
• the conditions at which the level of the drug in blood plasma can grow
• belonging to the Mongoloid race;
• simultaneous application of fibrates.

(See Sections "Features of application", "Interaction with other drugs and other types of interactions" and "Pharmacokinetics").

Interaction with other drugs and other interactions

Effect of concomitant drugs on rosuvastatin

Inhibitors of transport proteins

Rosuvastatin is a substrate for some transport proteins, including the hepatic transporter for the capture of OATP1B1 and the eflux transporter BCRP. The simultaneous use of rosuvastatin with drugs that inhibit these transport proteins may lead to an increase in the concentration of rosuvastatin in the blood plasma and an increased risk of myopathy (see Sections "Dosing and Administration", "Features of Use", "Interaction with Other Drugs and Other Mechanisms ", Table 2).

Cyclosporin

With simultaneous application of rosuvastatin and cyclosporin, the rosuvastatin AUC values were on average 7 times higher than those of healthy volunteers. Rosuvastatin is contraindicated in patients who simultaneously receive cyclosporine (see Section "Contraindications").

Simultaneous application does not affect the concentration of cyclosporine in the blood plasma.

Ezetimibe

The simultaneous use of rosuvastatin 10 mg and ezetimibe 10 mg in patients with hypercholesterolemia resulted in a 1.2 fold increase in rosuvastatin AUC (Table 2). However, the pharmacodynamic interaction between rosuvastatin and ezetimibe, which can lead to the occurrence of adverse reactions, can not be excluded (see Section "Features of application").

Gemfibrozil and other lipid-lowering drugs

The simultaneous use of rosuvastatin and gemfibrozil leads to an increase in the C max and AUC values of rosuvastatin by a factor of 2 (see the section on "Features of application").

Based on the data of special interaction studies, no significant pharmacokinetic interaction with fenofibrate is expected, but pharmacodynamic interaction may occur.

Gemfibrozil, fenofibrate, other fibrates and niacin (nicotinic acid) in lipid lowering doses (doses higher or equivalent to 1 g / day) increased the risk of myopathy with simultaneous application with HMG CoA reductase inhibitors, possibly due to the fact that the latter can cause development of myopathy with monotherapy. A dose of 40 mg is contraindicated in the simultaneous use of fibrates (see Sections "Contraindications" and "Features of application"). Also, patients should start with a dose of 5 mg.

Protease Inhibitors

Although the precise mechanism of interaction is unknown, the simultaneous use of protease inhibitors can significantly increase the exposure of rosuvastatin (see Table 2). For example, in a pharmacokinetics study, simultaneous administration of 10 mg rosuvastatin and a combined drug containing two protease inhibitors (300 mg atazanavir / 100 mg ritonavir) in healthy volunteers was accompanied by an increase in AUC and C max of rosuvastatin by approximately 3 and 7 times, respectively. The simultaneous use of rosuvastatin and certain combinations of protease inhibitors is possible after careful consideration of dose adjustment for rosuvastatin, based on the expected growth of rosuvastatin exposure (see Sections "Dosage and Administration", "Features of Use", "Interaction with Other Drugs and Other Interactions" Table 2).

Antacids

The simultaneous use of rosuvastatin and antacids in the form of a suspension containing aluminum and magnesium hydroxide leads to a decrease in the concentration of rosuvastatin in blood plasma by 50%. This effect was less pronounced when the antacid was used after 2:00 after taking rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin

Simultaneous use of rosuvastatin and erythromycin leads to a 20% decrease in AUC (0-t) rosuvastatin and 30% increase in C max of rosuvastatin. Such interaction may arise due to increased intestinal motility as a result of the use of erythromycin.

Enzymes of cytochrome P 450

The results of in vitro and in vivo studies have shown that rosuvastatin is not inhibited and does not induce cytochrome P 450 isozymes. In addition, rosuvastatin is a weak substrate for such isozymes. There were no clinically significant interactions between rosuvastatin and fluconazole (inhibitor CYP2C9 and CYP3A4) and ketoconazole (inhibitor of CYP2A6 and CYP3A4).

Interactions requiring dose adjustment for rosuvastatin

If you need to use the drug Romazik with other drugs that can increase the exposure of rosuvastatin, the dose of the drug Romazik needs to be adjusted. If it is expected that the exposure of the drug (AUC) will increase by about 2 or more times, Romazic should be started at a dose of 5 mg once a day. The maximum daily dose of the drug Romazik should be adjusted in such a way that the expected exposure of rosuvastatin does not exceed the exposure is noted when taking a dose of 40 mg / day without the use of medications interacting with the drug; For example, when applied with gemfibrozil, the dose of rosuvastatin will be 20 mg (1.9-fold increase in exposure), 10 mg when used with a combination of ritonavir / atazanavir (3.1-fold increase), while 5 mg with cyclosporine in 7.1 times).

table 2

The effect of concomitant medications on the exposure of rosuvastatin (AUC, in decreasing order of magnitude) according to published clinical research data

The dosage regimen of the drug interacts	The dosage regimen of rosuvastatin	Changes in AUC of rosuvastatin *
Cyclosporine from 75 mg twice a day to 200 mg twice daily, 6 months	10 mg once a day, 10 days	↑ 7.1 times
Atazanavir 300 mg / ritonavir 100 mg once a day, 8 days	10 mg, once	↑ 3,1 times
Simeprivir 150 mg once a day, 7 days	10 mg, once	↑ 2.8 times
Lopinavir 400 mg / ritonavir 100 mg twice daily, 17 days	20 mg once a day, 7 days	↑ 2.1 times
Gemfibrozil 600 mg twice a day, 7 days	80 mg, once	↑ 1,9 times
Eltrombopac 75 mg once a day, 5 days	10 mg, once	↑ 1.6 times
Darunavir 600 mg / ritonavir 100 mg twice daily, 7 days	10 mg once a day, 7 days	↑ 1,5 times
Tipranavir 500 mg / ritonavir 200 mg twice daily, 11 days	10 mg, once	↑ 1,4 times
Dronedarone 400 mg twice daily	unknown	↑ 1,4 times
Itraconazole 200 mg once daily, 5 days	10 mg, once	↑ 1.4 times **
Ezetimibe 10 mg once a day, 14 days	10 mg once a day, 14 days	↑ 1,2 times **
Fozamprenavir 700 mg / ritonavir 100 mg twice daily, 8 days	10 mg, once	↔
Aleglitazar 0.3 mg, 7 days	40 mg, 7 days	↔
Silymarin 140 mg three times a day, 5 days	10 mg, once	↔
Fenofibrate 67 mg three times a day, 7 days	10 mg, 7 days	↔
Rifampicin 450 mg once daily, 7 days	20 mg, once	↔
Ketoconazole 200 mg twice daily, 7 days	80 mg, once	↔
Fluconazole 200 mg once daily, 11 days	80 mg, once	↔
Erythromycin 500 mg four times a day, 7 days	80 mg, once	↓ 20%
Baikalin 50 mg three times a day, 14 days	20 mg, once	↓ 47%

* Data presented as a change in x times is the ratio between the application of rosuvastatin in combination and separately. The data presented in the form of a% change is the% difference in the ratio with rosuvastatin alone.

The magnification is indicated by the ↑ symbol, no changes ↔, the decrease is ↓.

** Several studies of interaction with various doses of rosuvastatin have been carried out, the table shows the most significant ratio.

Effect of rosuvastatin on concomitant medications

Antagonists of vitamin K

As in other HMG-CoA reductase inhibitors, an increase in the international normalized ratio (MHC) may be possible at the beginning of rosuvastatin administration or with an increase in its dose in patients concomitantly taking vitamin K antagonists (eg warfarin or another anticoagulant coumarin). Cancellation of rosuvastatin or a decrease in its dose may lead to a decrease in MFW. In such cases, the desired proper monitoring of the MES.

Oral contraceptives / hormone replacement therapy (HRT)

The simultaneous use of rosuvastatin and oral contraceptives leads to an increase in the AUC of estradiol and norgestrel by 26% and 34%, respectively. Such an increase in plasma concentrations should be taken into account when selecting doses of oral contraceptives. Pharmacokinetic data regarding patients taking rosuvastatin and HRT concomitantly are not present, therefore such effect can not be excluded. However, this combination was widely used during clinical trials, and the patients tolerated it well.

Other medicines

Based on data from specific interaction studies, clinically relevant interaction with digoxin is expected.

Lopinavir / ritonavir

The pharmacological study of the simultaneous use of a combined preparation and rosuvastatin containing two protease inhibitor ( 400 mg lopinavir / ritonavir 100 mg) in healthy volunteers was associated with about two-fold and five-fold increase in equilibrium parameters AUC (0-24) and C max for rosuvastatin according. Interaction between rosuvastatin and other protease inhibitors has not been studied.

children

interaction study was carried out only in adults . The degree of interaction in children is unknown .

application features

Effects on kidneys

Patients treated with rosuvastatin in higher doses, including 40 mg, observed proteinuria (detected using test strips) generally tubular origin, in most cases, was temporary or brief. Proteinuria was neither predictable factor of acute or progressive renal disease, so you should consider the renal function examination in patients receiving the drug at a dose of 40 mg.

Effect on skeletal muscle

It reported on the effect on skeletal muscle (myalgia, myopathy and rhabdomyolysis infrequently) in patients treated with rosuvastatin at any dose, and especially - in doses above 20 mg.

Very rarely reported cases of rhabdomyolysis when applying ezetimibe in combination with HMG CoA reductase. Pharmacodynamic interaction can not be excluded; care should be taken to carry out this combined treatment.

As in the case of other HMG- CoA reductase inhibitor, in the course of post-marketing of the drug was reported with a higher frequency of the occurrence of rhabdomyolysis associated with treatment with rosuvastatin, when using the 40 mg dose. There are reports of rare cases of immune -mediated necrotizing myopathy clinically resistant proksizmalnoyu muscle weakness and increased levels of serum CK, during treatment or after discontinuation of treatment with statins, including rosuvastatin. In this case, you may need additional neuromuscular and serologic studies, treatment with immunosuppressive drugs.

Determination of CK levels

Determining the level of CK (CC) should not be performed after intense exercise or when there are other possible reasons for the increase of the Criminal Code may lead to misinterpretation of results. If the source of the Criminal Code levels are significantly elevated (more than 5 times the upper limit of normal) should retest in 5-7 days. The drug should not be initiated if a second test confirms that the initial level of QC is more than 5 times the upper limit of normal.

before treatment

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

• renal dysfunction
• hypothyroidism
• hereditary muscular disease in his own system, or a family history
• a history - miotoksichnost when using other HMG-CoA reductase inhibitors or fibrates;
• alcohol abuse;
• ˃ age of 70 years;
• conditions that may increase the plasma level of the drug in the blood plasma (see sections "Dosage and Administration" "The interaction with other drugs and other forms of interaction" and "pharmacokinetics".);
• concurrent use of fibrates.

In these patients, the risk of the treatment should be weighed against the potential benefits, as well as the recommended clinical monitoring. If the source MC levels significantly increased ( more than 5 times the upper limit of normal) do not start treatment.

During treatment

Patients should be informed of the need to seek medical advice immediately if the unexpected occurs, pain, weakness or cramps in the muscles, especially if they are combined with malaise or fever. These patients should determine the level of QC. The treatment should be discontinued if CPK levels significantly increased (more than 5 times the upper limit of normal) or if the symptoms are severe and cause daily discomfort (even if the CPK level is less than 5 times the upper limit of normal). If the symptoms disappear and CPK levels return to normal limits, consideration should be given to re-use of rosuvastatin or an alternative HMG-CoA reductase inhibitors in low doses and under close supervision.

Regularly check the level of CPK in asymptomatic patients is not required. Very rarely reported cases of immune-mediated necrotising myopathy (IONM) during or after therapy with statins, including rosuvastatin. Clinical manifestations IONM is the weakness of the proximal muscles and increase blood serum CPK is retained even after the abolition of statins.

During the study there were no indications the growing influence on skeletal muscle in a small number of patients treated with rosuvastatin and concomitant therapy. However, the growth rate of myositis and myopathy observed in patients treated with other inhibitors of HMG-CoA reductase simultaneously with fibric acid derivatives including gemfibrozil, cyclosporin, nicotinic acid, azole antifungal agents, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy with concomitant use with some HMG-CoA reductase. Therefore, the combination of rosuvastatin and gemfibrozil is not recommended.

Advantages further changes in lipid levels, while the combined use of rosuvastatin with fibrates or niacin should be carefully weighed against the potential risks of using such combinations. The dose of 40 mg is contraindicated for simultaneous use with fibrate (see. Sections "Interaction with other drugs and other forms of interaction" and "side reaction").

Rosuvastatin should not be used in patients with severe acute conditions that may indicate myopathy or provoke the development of renal failure from rhabdomyolysis (such as sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures).

Effect on liver

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

It is recommended that liver function tests before starting treatment and at 3 months after initiation of treatment. Rosuvastatin should be discontinued or the dose reduced if the level of serum transaminases blood is more than 3 times the upper limit of normal. During post-marketing of the drug was reported with a higher frequency of the occurrence of serious reactions of liver (mainly an increase in serum transaminase levels) when applied dose of 40 mg.

Patients with secondary hypercholesterolemia, which originated as a result of hypothyroidism or nephrotic syndrome, treatment should be carried out before the underlying disease rosuvastatin application.

The Post-registration period rarely reported cases of fatal or non-fatal hepatic failure in patients treated with statins, including rosuvastatin. If during treatment with rosuvastatin develop severe liver disease with clinical symptoms and / or hyperbilirubinemia or jaundice, stop taking the drug. If other causes have been identified, you should not resume treatment with rosuvastatin.

Race

Pharmacokinetic studies indicate gain exposure among representatives of the Mongoloid race as compared to Caucasians. For these patients require dose correction rosuvastatin ( see. Sections "Dosage and Administration" "Contra" and "Pharmacokinetics"). For patients of Asian race Romaziku initial dose should be 5 mg. Increased concentration of rosuvastatin in plasma was seen in Asian patients (see. Sections "application features" and "Pharmacokinetics"). It is necessary to take into account the increased systemic exposure in patients Mongoloid race who have high cholesterol is not adequately controlled with doses up to 20 mg.

protease inhibitors

Increased systemic exposure to rosuvastatin observed in patients taking rosuvastatin concomitant with various protease inhibitors in combination with ritonavir. Should consider as the use of lipid-lowering via rosuvastatin in patients with HIV, the protease inhibitors are prepared and the possibility of increasing rosuvastatin concentrations in plasma at the start of therapy and at higher doses in patients Romaziku receiving protease inhibitors. Simultaneous use of the drug with protease inhibitors is not recommended, if not corrected Romaziku dose (see. Sections "Dosage and Administration" and "interaction with other drugs and other types of interactions").

Interstitial lung disease

On exceptional cases, interstitial lung disease were reported during the application of certain statins, especially after prolonged treatment (see. Section "Adverse reactions). The manifestations may include dyspnea, nonproductive cough and deterioration in general condition (weakness, weight loss and fever). If a patient is suspected interstitial lung disease, statin therapy should be discontinued.

Diabetes

Some evidence suggests that statins increase the level of blood glucose and in some patients, at high risk of developing diabetes in the future, may cause hyperglycemia, the level at which you want the proper treatment of diabetes. This threat, however, exceeds the reduction in the risk of vascular disorders with the use of statins and so it should not be a reason for discontinuation of therapy with statins. Patients at risk (fasting glucose 5.6-6.0 mmol / l, BMI> 30 kg / m 2, elevated levels of triglycerides, hypertension) should be set as a clinical and biochemical control on national guidelines.

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

In clinical studies it has shown rosuvastatin monotherapy does not cause a decrease in the base concentration in blood plasma cortisol levels and no effect on adrenal reserve. Care should be taken while the use of rosuvastatin and other medicines capable of reducing the level or activity of endogenous steroid hormones, such as ketoconazole, spironolactone and cimetidine.

Children

Qualification linear growth (growth), body weight, BMI (body mass index) and secondary characteristics of Tanner puberty by age 10 to 17 years, who were taking rosuvastatin limited period of 1 year. After 52 weeks of study treatment no effect on growth, body weight, BMI or puberty was found. (See. Section "Pharmacological"). Experience in clinical trials of the drug in children and pidlikam limited and long-term effects of the use of rosuvastatin (> 1 year) on puberty are unknown.

In a clinical study in children and adolescents who received rosuvastatin for 52 weeks, increased levels of CK> 10 times higher than the XIP and symptoms of the muscle after exercise or increased physical activity were observed more frequently compared to those in adults (see. Section "Side reaction").

Lactose intolerance

Patients with rare conditions such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption, should not use this drug.

Use during pregnancy or lactation.

Rosuvastatin is contraindicated during pregnancy and lactation.

Women of childbearing age must use appropriate contraception.

Since cholesterol and other products of the cholesterol biosynthesis essential for the development of the fetus, the potential risk of inhibition of HMG CoA reductase inhibitors exceeds the possible benefits of the drug during pregnancy. Data from animal studies of toxic effects on reproductive function are limited.

If pregnancy occurs during use of this product, treatment should be discontinued immediately.

Because another drug in this class passes into breast milk, and given that the HMG-CoA reductase inhibitors may cause serious adverse reactions in infants, women who need treatment for drug Romazik should be advised to refrain from breastfeeding. Information about the penetration of the drug into breast milk in humans there (see. Section "Contraindications").

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

Studies to determine the effect of rosuvastatin on the ability to drive vehicles or work with other mechanisms have not been conducted.

When driving vehicles or other mechanisms, it is necessary to take into account the possibility of dizziness during the treatment period.

Dosing and Administration

Before starting treatment, the patient should be prescribed a standard cholesterol-free diet, which should be followed during treatment. The dose should be selected individually, depending on the purpose of therapy and the effectiveness of treatment, guided by the current agreed recommendations.

The drug can be used at any time of the day, regardless of food intake. The tablet is swallowed whole, washed down with water.

Treatment of hypercholesterolemia

The recommended initial dose is 5 mg or 10 mg orally once a day for patients who are the first to use statins, and also for patients transferred from taking other HMG-CoA reductase inhibitors. When selecting the initial dose of each individual patient, the level of cholesterol and the risk of cardiovascular complications in the future should be taken into account, as well as the potential risk of adverse reactions. If necessary, the dose can be gradually increased, but not earlier than 4 weeks later. Due to the increased incidence of adverse reactions with a dose of 40 mg compared with smaller doses (see the Section "Adverse Reactions"), the question of titration up to a maximum dose of 40 mg should be considered only for patients with severe hypercholesterolemia with a high risk of developing cardiovascular complications (especially in patients with familial hypercholesterolemia) who do not achieve the desired result of treatment with a dose of 20 mg and who will be under regular follow-up (see Table 1). ECTION "Features of the application"). When administering a dose of 40 mg, specialist supervision is recommended.

Prevention of cardiovascular diseases

In the course of the study, a decrease in the risk of developing cardiovascular diseases was used in a dose of 20 mg per day.

Use in elderly patients

For patients aged 70 years, the recommended dose is 5 mg (see section "Features of application").

There is no need for another dosage adjustment, depending on age.

Dosing for patients with impaired renal function

There is no need for dose adjustment for patients with impaired renal function of mild and moderate severity.

For patients with impaired renal function of moderate severity, the recommended initial dose is 5 mg (creatinine clearance <60 mL / min). A dose of 40 mg is contraindicated in patients with impaired renal function of moderate severity. Contraindicated the use of rosuvastatin in any dose in patients with impaired renal function of a serious degree (see Sections "Contraindications" and "Pharmacokinetics").

Dosing for patients with impaired liver function

In patients with a score of 7 or lower on the Child-Pugh scale, systemic exposure to rosuvastatin is NOT enhanced.However, there was an increase in exposure in patients with a score of 8 or 9 on the Child-Pugh scale (see Section "Pharmacokinetics"). Such patients should consider the examination of kidney function (see section "Features of application"). There is no experience in administering the drug to patients with a score greater than 9 on the Child-Pugh scale. Rosuvastatin is contraindicated in patients with active liver disease.

Race

Strengthening of systemic exposure was observed in patients of the Mongoloid race. For such patients, the recommended dose is 5 mg (see Sections "Contraindications", "Features of Use" and "Pharmacokinetics").

The drug in a dose of 40 mg to such patients is contraindicated.

Genetic polymorphism

Certain types of genetic polymorphism can lead to increased exposure of rosuvastatin (see Section "Pharmacokinetics"). Patients with a known presence of such types of polymorphism are advised to use a smaller dose of rosuvostatin.

Dosing for patients with a tendency to develop myopathy

For patients with a propensity to develop myopathy, the recommended dose is 5 mg. In such patients, a dose of 40 mg is contraindicated (see Section "Contraindications").

Simultaneous application

Rosuvastatin is a substrate for various transport proteins (eg, OATP1B1 and BCRP). The risk of myopathy (including rhabdomyolysis) increases with the simultaneous use of rosuvastatin with certain drugs that can increase the concentration of rosuvastatin in plasma due to interaction with these transport proteins (eg, cyclosporine and certain protease inhibitors, including combinations of ritonavir with atazanavir, lopinavir and / or tipranavir, see the sections on "Features of Use" and "Interaction with Other Drugs and Other Interactions"). If possible, consider the use of alternative medicines and, if necessary, temporarily discontinue therapy with Romazic. If the concomitant use of these drugs with rosuvastatin can not be avoided, the benefit and risk of concomitant use should be carefully weighed and the dose of Romazic should be adjusted accordingly (see Section "Interaction with Other Drugs and Other Interactions").

Children

The use of the drug in children should be done only by a specialist.

Applied to children and adolescents aged 10 to 17 years (boys at the stage of development II and above Tanner and girls in which menstruation began less than a year ago).

The initial daily dose for children and adolescents with heterozygous familial hypercholesterolemia is 5 mg per day. The drug is usually taken orally at doses of 5 mg to 20 mg once daily. Increase the dose should be in accordance with the individual's responses to the treatment and tolerability of the drug, following the recommendations for the treatment of children (see section "Features of application"). Before starting treatment with rosuvastatin, children and adolescents should be prescribed a standard hypocholesterolemic diet, which patients must adhere to during treatment. The safety and efficacy of the drug in doses greater than 20 mg in this population have not been investigated.

Tablets of 40 mg are not prescribed for children.

Children under 10 years old

The experience of treating children under the age of 10 is limited to the use of the drug in a small number of patients (aged 8 to 10 years) with homozygous familial hypercholesterolemia. Thus, the drug Romazik is not recommended for children under 10 years.

Overdose

There is a specific treatment in case of an overdose. In case of overdose, symptomatic treatment of the patient, as well as supporting measures if necessary, should be performed. It is necessary to monitor the function of the liver and the level of CK. It is unlikely that hemodialysis will be effective.

Adverse Reactions

Adverse reactions that were observed with rosuvastatin were usually mild. In studies less than 4% of patients taking rosuvastatin discontinued treatment due to adverse reactions.

Undesirable reactions are classified by frequency and system-organ classes (SOK). Frequencies of adverse reactions are classified as follows:

often (from ≥ 1/100 to <1/10);

infrequently (from ≥ 1/1 000 to <1/100);

rarely (from ≥ 1/10 000 to <1/1000);

very rarely (<1 / 10,000)

unknown (can not be determined from available data).

On the part of the blood and lymphatic system

Rarely thrombocytopenia

From the immune system

Rarely hypersensitivity reactions, including angioedema.

From the endocrine system

Often diabetes mellitus (The frequency depends on the presence of risk factors (fasting glucose ≥ 5.6 mmol / L, BMI ˃ 30 kg / m 2, elevated triglyceride levels, arterial hypertension in anamenia).

mental disorders

The frequency is unknown: depression.

From the nervous system

Often a headache, dizziness.

Very rarely polyneuropathy, loss of memory.

The frequency is unknown: peripheral neuropathy, sleep disorders (including insomnia and nightmares).

On the part of the respiratory, thorax and mediastinal organs:

The frequency is unknown: cough, dyspnea.

From the gastrointestinal tract

Often constipation, nausea, pain in the abdomen.

Rarely pancreatitis.

Frequency unknown: diarrhea.

From the digestive system:

Rarely increases the level of hepatic transaminases.

Very rarely jaundice, hepatitis.

From the skin and subcutaneous tissue

Infrequent itching, rashes and hives.

The frequency is unknown: Stevens-Johnson syndrome.

From the side of skeletal musculature and connective tissue

Often myalgia.

Rarely, myopathy (including myositis) and rhabdomyolysis.

Very rarely arthralgia.

The frequency is unknown: violations of the tendons, sometimes disruption, immuno-mediated necrotizing myopathy.

From the side of the kidneys and the urinary system:

Very rarely hematuria.

From the side of the reproductive system and mammary glands

Very rarely gynecomastia.

Disturbance of general condition and associated with the method of application of the drug

Often asthenia.

Frequency unknown: edema.

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

Influence on the kidneys

In patients treated with rosuvastatin, proteinuria was observed (found using test strips), usually of tubular origin. A change in the amount of urine protein, from the absence or traces of protein in ++ or more, was observed in <1% of patients at certain times during treatment at doses of 10 mg and 20 mg, and also in approximately 3% of patients receiving a dose of 40 mg. When using the drug at a dose of 20 mg there was a slight increase in the amount of protein, from the absence or traces of the protein to +. In most cases, proteinuria decreased or disappeared spontaneously with continued therapy, nor was it a predictable factor in the occurrence of acute or progressive kidney disease.

Hematuria was reported; According to research, their frequency is low.

Effect on skeletal muscles

Effects on skeletal muscle have been reported: myalgia, myopathy (including myositis) and rarely rhabdomyolysis in patients treated with rosuvastatin at any dose, especially at doses above 20 mg.

A dose-dependent increase in MC levels was observed in patients taking rosuvastatin; most of the cases were mild, asymptomatic and transient. If the level of CK increases (more than 5 times compared with the upper limit of the norm), treatment should be discontinued (see section "Features of application").

Effects on the liver

As with other HMG-CoA reductase inhibitors, a dose-dependent increase in transaminase activity was observed in a small number of patients who used rosuvastatin; most of the cases were mild, asymptomatic and transient. When rosuvastatin was used, there was also an increase in HbA1c levels.

Against the background of the use of some statins, there were such side effects:

Disorder of sexual function.

Individual cases of interstitial lung disease, especially with prolonged use (see Section "Features of application").

The frequency of reports of rhabdomyolysis, serious violations of the kidneys and liver (mainly increase the activity of hepatic transaminases) is greater when using the drug in a dose of 40 mg.

In the process of the post-registration application of the Romazik preparation, an undesirable reaction was identified, such as lethal and non-lethal hepatic insufficiency. Since this reaction was reported spontaneously from a population of an indeterminate amount, it is impossible to reliably estimate its frequency or to establish the presence of a cause-and-effect relationship with the use of the drug.

Occasionally, in the post-registration period, violations of cognitive functions were reported (eg, memory impairment, forgetfulness, amnesia, memory impairment, confusion), which are associated with the use of statins. Such cognitive problems have been reported in connection with all statins. The phenomena reported in the reports are usually of a mild nature and occur after the abolition of statins, and also have a different time before the onset of symptoms (from 1 day to years) and until the symptoms disappear (median 3 weeks).

Children

Elevated levels of CK> 10 times the upper limit of normal and muscle symptoms after physical exertion or increased physical activity were observed more often in a 52-week clinical trial involving children and adolescents than adults (see "Features of Use" section). However, the safety profile of rosuvastatin in children and adolescents was similar to that of adults.

Shelf life

2 years.

Storage conditions

Store at a temperature of no higher than 25 ° C in a dry, dark place. Keep out of the reach of children.

Packaging

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

Category of leave

On prescription.