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

Excipients: lactose anhydrous - 93,525 mg, calcium carbonate - 22,500 mg, crospovidone - 4,050 mg, potato starch - 2,500 mg, magnesium stearate - 1,350 mg, silicon dioxide colloid - 0,675 mg.

Composition of the tablet shell: Opapray II white (85F18422) - 5,000 mg (polyvinyl alcohol -2,000 mg, titanium dioxide 1,250 mg macrogol-3350 -1,010 mg, talc 0.740 mg).

1 tablet, film-coated, 20 mg contains:

Tablet core composition:

Active substance: rosuvastatin calcium - 20,800 mg, calculated as rosuvastatin - 20,000 mg.

Excipients: lactose anhydrous - 187,050 mg, calcium carbonate - 45,000 mg, crospovidone - 8,100 mg, potato starch - 5,000 mg, magnesium stearate 2,700 mg, silicon dioxide colloid - 1,350 mg.

Composition of the tablet shell: Opapray II white (85F18422) - 10,000 mg (polyvinyl alcohol - 4,000 mg, titanium dioxide - 2,500 mg, macrogol-3,350 - 2,020 mg, talc-1,480 mg).

1 tablet, film-coated, 40 mg contains:

Tablet core composition:

Active substance: rosuvastatin calcium - 41,600 mg, in terms of rosuvastatin - 40,000 mg.

Excipients: lactose anhydrous - 374.100 mg, calcium carbonate - 90.000 mg, crospovidone - 16,200 mg, potato starch - 10,000 mg, magnesium stearate - 5,400 mg, silicon dioxide colloid - 2,700 mg.

Composition of the tablet shell: Opapray II white (85F18422) - 20.000 mg (polyvinyl alcohol - 8.000 mg, titanium dioxide - 5.000 mg, macrogol-3350 - 4.040 mg, talc - 2.960 mg).

Description:

Tablets 10 mg: The tablets are round, biconvex, covered with a film coat of white or almost white color. On the cross section - the core is white or almost white.

Tablets of 20 mg: The tablets are round, biconvex, covered with a film coat of white or almost white color, with a risk on one side. On the cross-section, the nucleus is white or almost white in color.

Tablets 40 mg: Tablets are oval, biconvex, covered with film

shell white or almost white, with a risk on one side and embossed in the form of character <<f>> - on the other.On the cross section - the core is white or almost white.

Pharmacotherapeutic group:lipid-lowering agent - 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, which converts 3-hydroxy-3-methylglutaryl coenzyme A into mevalonate, the precursor of cholesterol. The main target of the action of rosuvastatin is the liver, where the synthesis of cholesterol (CS) and catabolism of low-density lipoproteins (LGI! P) is carried out.

Rosuvastatin increases the number of "hepatic" JIOPP receptors on the cell surface, increasing the uptake and catabolism of LDL, which leads to inhibition of the synthesis of very low density lipoproteins (VLDL), thereby reducing the total amount of LDL and VLDL.

Rosuvastatin reduces elevated concentrations of LDL cholesterol (LDL-C). total cholesterol and griglycerides (TG). increases the concentration of high density lipoproteins (HDL-C) cholesterol, and also reduces the concentrations of apolipoprotein B (ApoB), cholesterol-non-HDL, cholesterol-VLDL, and VLP and increases the concentration of apolipoprotein A-I (ApoA-1).reduces the ratio of cholesterol-LPI1P / HDL-C, total cholesterol / HDL-C and HDL-CSL / HDL cholesterol and the Apov / ApoA-1 ratio.

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

Pharmacokinetics:

Suction and distribution

The maximum concentration of rosuvastatin in the blood plasma is reached approximately 5 hours after oral administration. Absolute bioavailability is approximately 20%.

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

Metabolism

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

The main revealed metabolites of rosuvastatin are N-detyl and lactone metabolites. N-detyl is about 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

About 90 % of the dose of rosuvastatin is excreted unchanged through the intestine (including absorbed and nonabsorbable rosuvastatin). The rest is excreted by the kidneys. Half-life (T1 / 2) from plasma is approximately 19 hour. T1 / 2 does not change with increasing dose of the drug. The average geometric plasma clearance is approximately 50 l / h (coefficient of variation of 21.7%). As in the case of other inhibitors of HMG-CoA reductase. in the process of "hepatic" seizure of rosuvastatin, a membrane cholesterol transporter is involved, which plays an important role in the hepatic elimination of rosuvastatin.

Linearity

The systemic influence of rosuvastatna increases proportionally to the dose.

Pharmacokinetic parameters do not change with daily intake of the drug.

Special populations of patients.

Age and gender

Sex and age have no clinically significant effect on the pharmacokinetic parameters of rosuvastatin.

Ethnic groups

Pharmacokinetic studies showed approximately a twofold increase in the median AUC (area under the concentration-time curve) and C_m_Oh (the maximum concentration in the blood plasma) is rosuvastatna in patients of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with Caucasians; Hindus show an increase in median AUC and C_m_Oh in 1.3 times. Pharmacokinetic analysis did not reveal clinically significant differences in pharmacokinetics among Caucasians and representatives of the Negroid race.

Renal insufficiency

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

When conducting studies in patients with varying degrees of liver failure, there was no increase in T_1/2 is rosuvastatna in patients with a score of 7 or lower on the Child-Pugh scale. In two patients with scores of 8 and 9 on the Child-Pugh scale, an increase in T_1/2at least 2 times. Experience with rosuvastatna in patients with a score above 9 on the Child-Pyo scale is not available. Genetic polymorphism

Inhibitors of HMG-CoA reductase, including, rosuvastatin, bind to transport proteins OATP1B1 (the polypeptide of the transport of organic anions involved in the capture of the stats by hepatocytes) and BCRP (efflux conveyor). In carriers of genotypes SLCOIBI (OATP1B1) with.521CC and ABCG2 (BCRP) C.421AA there was an increase AUC rosuvastatna in 1.6 and 2.4 times, respectively, compared with carriers of genotypes SLCOIBI from.521TT and ABCG from.421CC.

Indications:

Primary hypercholesterolemia according to Fredrickson classification (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as a supplement to the diet,when the diet and other non-pharmacological methods of treatment (for example, physical exercises, weight loss) are insufficient:

- Family homozygous hyperholesterolemia as a supplement to diet and other lipid-lowering therapy (eg, LDL-apheresis), or in cases where such therapy is not effective enough;

- Hypertriglyceridemia (type IV according to Fredrickson's classification) as a supplement to the diet;

- To slow the progression of atherosclerosis as a supplement to the diet in patients who are shown therapy to reduce the concentration of total cholesterol and LDL-C;

- Primary prevention of major cardiovascular complications (stroke, myocardial infarction, arterial revascularization) in adult patients without clinical signs of IHD. but with an increased risk of developing it (age over 50 for men and over 60 for women, an elevated concentration of C-reactive protein (> 2 mg / L), with at least one of additional risk factors such as hypertension. concentration of HDL-C, smoking, family history of early onset of CHD).

Contraindications:

For the preparation rosuvastatin in a daily dose of 10 mg and 20 mg:

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

- rare hereditary intolerance to galactose, deficiency of lactase and glucose-galactose malabsorption (the preparation contains lactose);

- liver diseases in the active phase, including persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times higher than the upper limit of the norm (VGN));

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

- myopathy;

- simultaneous administration of cyclosporine;

in women: pregnancy, lactation, lack of adequate methods of contraception;

- patients who are predisposed to the development of myotoxic complications

- children's age till 18 years.

- For the preparation rosuvastatin in a daily dose of 40 mg:

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

- rare hereditary intolerance to galactose, deficiency of lactase and glucosogalactose malabsorption (the preparation contains lactose);

- simultaneous administration of cyclosporine;

- in women: pregnancy, lactation, lack of adequate methods of contraception;

- liver diseases in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3-fold compared with IGN);

- patients with risk factors for myopathy / rhabdomyolysis, namely:

- renal failure of moderate severity (CC less than 60 ml / min),

- hypothyroidism,

- personal or family anamnesis of muscular diseases,

- m flow and puncture against the background of taking other inhibitors of HMG-CoA reductase or fibrates in the anamnesis,

- excessive use of alcohol,

- state, which can lead to an increase in plasma concentration of rosuvastatin,

- simultaneous reception of fibrates.

- patients of the Mongoloid race:

- children's age till 18 years.

Carefully:For tablets 10 and 20 mg: myopathy / rhabdomyolysis risk-renal failure, hypothyroidism, personal or family history of hereditary muscle diseases and a previous history of muscle toxicity with other HMG-CoA reductase inhibitors or fibrates; excessive use of alcohol; age over 65 years: conditions in which there is an increase in plasma concentration of rosuvastatna; racialaffiliation (Mongoloid race); simultaneous application with fibrates; liver disease in history; sepsis; arterial hyiotension; extensive surgical interventions, trauma: severe metabolic, endocrine or electrolyte disorders; uncontrolled convulsive seizures.

For tablets 40 mg: renal failure of mild severity (CC greater than 60 ml / min); age over 65; liver disease in history; sepsis; arterial hypotension; extensive surgical interventions, trauma; severe metabolic, endocrine or electrolyte disorders: uncontrolled convulsive seizures.

Patients with hepatic insufficiency

Data or experience of the drug in patients with hepatic impairment and with more than 9 points on the Child-Pugh scale is not available.

Pregnancy and lactation:

Rosuvastatin is contraindicated in pregnancy and during breastfeeding.

Women of reproductive age should apply adequate methods

contraception.

Because cholesterol and other cholesterol biosynthesis products are important for fetal development, the potential risk of inhibiting HMG-CoA reductase exceeds the benefit of using the drug in pregnant women.

In case of pregnancy in the process of therapy, taking the drug should be stopped immediately.

Data on the allocation of rosuvastatin to breast milk are not available, so during breast-feeding, the drug should be discontinued (see section "Contraindications").

Dosing and Administration:

Inside, do not chew and do not grind the tablet, swallow whole, squeezed water. The drug can be administered at any time of the day, regardless of food intake. Before starting therapy with the drug Rosuvastatin the patient should begin to observe the standard hypocholesterolemic diet and continue to observe it during treatment. The dose of the drug should be selected individually, depending on the purpose of therapy and therapeutic response to treatment, taking into account modern generally accepted recommendations on target lipid concentrations.

The recommended initial dose for patients starting to take the drug, or for patients transferred from other HMG-CoA reductase inhibitors, should be 5 mg or 10 mg rosuvastatin once a day. When choosing the initial dose, one should be guided by the individual concentration of cholesterol and take into accountpossible risk of cardiovascular complications, as well as evaluate the potential risk of side effects. If necessary, the dose may be increased to greater after 4 weeks. In connection with the possible development of side effects when taken in a dose of 40 mg. compared with lower doses of the drug, increasing the dose to 40 mg. after additional dose intake above the recommended initial dose for 4 weeks of therapy. can only be performed in patients with severe hypercholesterolemia and a high risk of developing cardiovascular complications (especially in patients with familial hypercholesterolemia) who did not achieve the desired result of therapy with a 20 mg dose and who will be under the supervision of a specialist. It is recommended especially careful monitoring of patients receiving the drug in a dose of 40 mg.

It is not recommended to administer the drug at a dose of 40 mg to patients who have not previously consulted a doctor. After 2-4 weeks of therapy and / or with an increase in the dose of the drug rosuvastatin it is necessary to monitor the lipid metabolism (if necessary, dose adjustment is required).

To patients of advanced age no dose adjustment is required.

Have patients with renal insufficiency mild or moderate severity, dose adjustment is not required. In patients with severe renal insufficiency (CC less than 30 ml / min), rosuvastatin is contraindicated. Contraindicated use of the drug in a dose of 40 mg to patients with moderate impairment of kidney function (KK 30-60 ml / min). Patients with moderate impairment of renal function are recommended an initial dose of 5 mg.

Patients with hepatic insufficiency: rosuvastatin contraindicated in patients with liver disease in the active phase.

Special populations.

Ethnic groups. When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, there was an increase in the systemic concentration of rosuvastatin among patients of the Mongoloid race. This fact should be considered when prescribing the drug rosuvastatin to these groups of patients. When appointing doses of 10 mg and 20 mg, the recommended initial dose for patients of the Mongoloid race is 5 mg. Contraindicated appointment of the drug in a dose of 40 mg to patients of the Mongoloid race (see the section "Contraindications"). Genetic polymorphism. In carriers of genotypes SLCO1B1 (OATP1B1) p.521N and ABCG2 (BCRP) C.421AA there was an increase AUC rosuvastatin compared with carriers of genotypes SLCOIBI p.521TT and ABCG2 p.421S. For patients carrying genotypes с.521СС or с.421АА the recommended maximum dose of rosuvastatin is 20 mg once a day (see sections "Pharmacokinetics", "Special instructions" and "Interaction with other medicinal products").

Patients who are predisposed to myopathy. Contraindicated the appointment of the drug in a dose of 40 mg to patients with factors that may indicate a predisposition to the development of myopathy (see section "Contraindications"). When appointing doses of 10 mg and 20 mg, the recommended initial dose for this group of patients is 5 mg (see the section "Contraindications").

Concomitant therapy. Rosuvastatin binds to various transport proteins (in particular, OATP1B1 and BCRP). When rosuvastatin is used together with medicinal products (such as ciclosporin, some HIV protease inhibitors, including a combination of ritonavir with atazanavir, lopinavir and / or tipranavir) that increase the concentration of rosuvastatin in blood plasma by interacting with transport proteins,may increase the risk of myopathy (including rhabdomyolysis) (see sections "Special instructions" and "Interaction with other medicinal products"). In such cases, the possibility of prescribing alternative therapy or temporary discontinuation of rosuvastatin should be assessed. If the use of the above drugs is necessary, the ratio of benefit and risk of concomitant therapy with rosuvastatin should be evaluated and the possibility of reducing its dose should be considered (see section "Interaction with Other Drugs").

Side effects:

The side effects observed with the administration of rosuvastatin are usually not very pronounced and go away on their own. As with other inhibitors of HMG-CoA reductase. the incidence of side effects is mainly dose-dependent.

The incidence of adverse events is as follows: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10 000 , <1/1000), very rarely (<1/10 000). frequency, unspecified (can not be calculated from available data).

From the central nervous system: often - headache, dizziness,asthenic syndrome; infrequently - depression, anxiety, sleep disturbances, including insomnia and nightmarish dreams, paresthesia; very rarely - peripheral neuropathy, loss or loss of memory.

From the digestive system: often - nausea, constipation, abdominal pain; infrequently -

vomiting, diarrhea, flatulence; rarely - pancreatitis, increased activity of "hepatic" transmnaz; very rarely - hepatitis, jaundice.

From the respiratory system: Unspecified frequency - cough, shortness of breath.

From the endocrine system: often - type 2 diabetes mellitus.

From the musculoskeletal system: often - myalgia; rarely - myopathy (including myositis), rhabdomyolysis; very rarely - arthralgia; Unspecified frequency - immuno-mediated pecrotizing myopathy.

From the reproductive system and the breast: unspecified frequency - gynecomastia, sexual dysfunction.

On the part of the hematopoiesis system: Unspecified frequency - thrombocytopenia.

Allergic reactions: infrequently - itching, hives, rashes: rarely - angioedema.

From the skin and subcutaneous fat: Unspecified frequency - Stevens-Johnson syndrome.

From the urinary system: often - proteinuria (mainly in patients receiving a dose of 40 mg), decreasing during therapy and not associated with the onset of kidney disease, urinary tract infection; very rarely - hematuria.

Other: frequency of peripheral edema.

Laboratory indicators: increased activity of CKK, glucose concentration, bilirubin, glycosylated hemoglobin, activity of gamma-glutamylgranferase, alkaline phosphatase, thyroid dysfunction.

With prolonged use of rosuvastatin, single cases have been reported interstitial lung disease.

Overdose:

With the simultaneous administration of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change.

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 functions 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:

Effect of the use of other drugs on rosuvastatin

Inhibitors of transport proteins: rosuvastatin binds to certain transport proteins, in particular, OATP1B1 and BCRP. The concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the concentration of rosuvastatin in plasma and an increased risk of myopathy (see Table 1 and the sections "Dosing and Administration" and "Specific Guidance").

Cyclosporine: with simultaneous application of rosuvastatin and cyclosporine AUC rosuvastatna was on average 7 times higher than the value that was noted in healthy volunteers (see Table I). Does not affect the plasma concentration of cyclosporine. Rosuvastatin contraindicated in patients receiving ciclosporin (see section "Contraindications").

Inhibitors of the human immunodeficiency virus (HIV) protease: despite the fact that the exact mechanism of interaction is unknown, co-administration of HIV protease inhibitors can lead to a significant increase in rosuvastatin concentration (see Table I).

A pharmacokinetic study on the simultaneous use of 20 mg rosuvastatna with a combined preparation containing two HIV protease inhibitors (400 mg lopinavir / 100 mg ritonavir) in healthyvolunteers led to approximately a two-fold and five-fold increase AUCo-24 and Cmax rosuvastatna accordingly. Therefore, simultaneous administration of rosuvastatin and HIV protease inhibitors in the treatment of patients with HIV infection is not recommended (see the sections "Dosing and Administration", "Specific guidance", Table 1).

Gemfibrozil and other lipid-lowering drugs: the combined use of rosuvastatin and gemfibrozil leads to an increase in Cmax rosuvastatna in blood plasma and AUC rosuvastatna in 2 times (see section "Special instructions"). Based on the data on the specific interaction, no pharmacokinetically significant interaction with fenofibrates is expected. possibly pharmacodynamic interaction. Gemfibrozil, fenofibrate, other fibrates and lio-reducing doses of nicotinic acid increased the risk of myopathy with simultaneous use with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy when used as monotherapy. If the drug is simultaneously taken with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day), the initial dose of 5 mg is recommended for patients.Receiving a dose of 40 mg is contraindicated when coadministered with fibrates (please refer "Contraindications", "Dosing", "Cautions").

Ezetimibe: simultaneous application of rosuvastatin in a dose of 10 mg and ezetimibe in a dose

10 mg was accompanied by an increase AUC rosuvastatin in patients with

hypercholesterolemia (see Table 1). It is impossible to exclude the increase in risk

side effects due to the pharmacodynamic interaction between

rosuvastatin and ezthrmib.

Antacids: simultaneous use of rosuvastatin and suspensions of antacids containing magnesium hydroxide and aluminum 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 this interaction has not been studied.

Erythromycin: simultaneous application of rosuvastatin and erythromycin leads to a decrease AUC rosuvastatin by 20% and Cmax rosuvastatin by 30%. Such interaction can arise as a result of increased intestinal motility caused by the intake of erythromycin.

Isozymes of the cytochrome P450 system: 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. Therefore, rosuvastatin is not expected to interact with other drugs at the metabolic level with the participation of cytochrome P450 isoenzymes. There was no clinically significant interaction between rosuvastatin and fluconazole (isozyme inhibitor CYP2C9 and CYP3A4) and ketoconazole (inhibitor of isoenzymes CYP2A6 and CYP3A4).

Fusidic acid: Special studies on the interaction of rosuvastatin and fusidic acid have not been conducted. Reports of cases of rhabdomyolysis in patients receiving rosuvastatin and fusidic acid were reported. Such patients require careful follow-up and, possibly, temporary withdrawal of rosuvastatin.

Interaction with drugs, which requires correction of the dose of rosuvastatin (see Table 1)

Table I. Effect of concomitant therapy on the concentration of rosuvastatin.

Complementary therapy regimen	Mode of taking rosuvastatin		Change AUC rosuvastatin
Cyclosporine 75-200 mg 2 times a day, 6 months.	10 mg 1 time per day, 10 days		An increase of 7.1 times
Atazanavir 300 mg / ritonavir 100 mg 1 time per day, 8 days		10 mg once		Increase 3.1 times

Lopinavir 400 mg / ritonavir 100 mg 2 times per day, 17 days		20 mg 1 time per day, 7 days		Increase 2.1 times
Gemfibrozil 600 mg 2 times a day, 7 days		80 mg once		Increase 1.9 times
Eltrombopag 75 mg 1 time per day, 10 days		10 mrs		Increase 1.6 times
Darunavir 600 mg / ritonavir 100 mg 2 times per day, 7 days		10 mg 1 time per day .. 7 days		Increase by 1.5 times
Tipranavir 500 mg / ritonavir 200 mg 2 times per day, 11 days		10 mg once		Increase by 1.4 times
Dronedarone 400 mg 2 times a day.		No data		Increase by 1.4 times
Itraconazole 200 mg once a day, 5 days		10 mg or 80 mg once		Increase by 1.4 times
Ezetimibe 10 mg 1 time per day, 14 days		10 mg 1 time per day, 14 days		Increase by 1.2 times
Fosamprenavir 700 mg / ritonavir 100 mg 2 times per day, 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 mrs		Without changes
Fenofibrate 67 mg 3 times in su, 7 days		10 mg. 7 days		Without changes
Rifampin 450 mg 1 time per day .. 7 days		20 mg once		Without changes
Ketoconazole 200 mg 2 times per day, 7 days		80 pennies		Without changes
Fluconazole 200 mg once a day .. 11 days		80 pennies		Without changes
Erythromycin 500 mg 4 times per day, 7 days		80 mg once		Decrease by 28%
Baikalin 50 mg 3 times a day, 14 days		20 mi^- once		Decrease by 47%

Effect of rosuvastatin and other medications

Antagonists of vitamin K: the initiation of rosuvastatin therapy or an increase in the dose of the drug in patients receiving both vitamin K antagonists (for example, warfarin), can lead to an increase in the International Normalized Relationship (MHO). The cancellation of rosuvastatin or a decrease in the dose of the drug may lead to a decrease Ml 10. In such cases, control is recommended MHO.

Oral contraceptives / hormone replacement therapy: simultaneous

the use of rosuvastatin and oral contraceptives increases AUC ethinylestradiol and AUC norgestrel by 26% and 34% respectively. Such an increase in plasma concentration should be taken into account when choosing a dose of oral contraceptives. Pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement therapy are not available, therefore, it is impossible to exclude a similar effect when using this combination.However, this combination was widely used during clinical trials and was well tolerated by patients.

Other medicines: no clinically significant interaction between rosuvastatin and digoxin is expected.

Special instructions:

Influence on the kidneys

In patients receiving high doses of rosuvastatin (mainly 40 mg), tubular proteinuria was observed, which, in most cases, was transient. Such proteinuria did not indicate acute kidney disease or progression of kidney disease. In patients taking the drug at a dose of 40 mg, it is recommended to monitor the performance of kidneys during treatment.

FROMabout the side of the musculoskeletal system

When rosuvastatin was used in all dosages and, in particular when taking doses of the drug in excess of 20 mg, the following effects on the musculoskeletal system were reported: myalgia, myopathy, in rare cases rhabdomyolysis.

Determination of CKK activity

Determination of the activity of CKK should not be performed after intensive physical exertion or in the presence of other possible causes of increased activity of CK.which can lead to incorrect interpretation of the results. In the event that the initial activity of CK is significantly increased (5 times higher than VGN), after 5-7 days, a second measurement should be made. Do not start therapy if a second test confirms the baseline CK activity (more than 5 times higher than the VLN).

Before the start of therapy

With the appointment of rosuvastatin. as with the administration of other HMG-CoA reductase inhibitors, caution should be exercised in patients with existing risk factors for myopathy / rhabdomyolysis (see "With caution"), the risk-to-benefit ratio of therapy should be considered and clinical observation performed.

During therapy

The patient should be informed of the need to report immediately to the doctor about cases of sudden onset of muscle pain, muscle weakness, or spasms, especially in combination with malaise and fever. In such patients, the activity of CK should be determined. Therapy should be discontinued if the activity of CK is significantly increased (more than 5 times as compared with ULN), or if the symptoms from the muscles are pronounced and cause daily discomfort (even if the activity of CK is increased by no more than 5 times compared to the VGN ).If symptoms disappear and CPK activity returns to normal, re-administration of rosuvastatin or other HMG-CoA reductase inhibitors in smaller doses should be considered with careful monitoring of the patient. Routine monitoring of the activity of CKK in the absence of symptoms is inappropriate. Very rare cases of immuno-mediated necrotizing myopathy with clinical manifestations in the form of persistent weakness of proximal muscles and increased activity of CKK in the serum during treatment or with discontinuation of taking statias were noted. rosuvastatna. It may be necessary to conduct additional studies of the muscular and nervous system, serological studies, as well as immunosuppressive therapy.

There were no signs of an increase in the effect on skeletal musculature when taking rosuvastatin and concomitant therapy. However, an increase in the incidence of myositis and myopathy in patients taking other HMG-CoA reductase inhibitors in combination with fibrin acid derivatives, including gemfibrozil, ciclosporin, nicotinic acid in lipid-lowering doses (more than 1 g / day), azole antifungal agents, HIV protease inhibitors and macrolide antibiotics.Gemfibrozil increases the risk of myopathy when combined with certain HMG-CoA reductase inhibitors. Thus, simultaneous use of the drug is not recommended rosuvastatin and gemfibrozil. Care should be taken to weigh the risk-to-benefit ratio when rosuvastatin and fibrates or lipid-lowering doses of nicotinic acid are used together. Contraindicated rosuvastatna reception in a dose of 40 mg in conjunction with fibrates (see the section "Interaction with other drugs").

In 2-4 weeks after the start of treatment and / or with an increase in the dose of rosuvastatin

it is necessary to monitor the lipid metabolism (if necessary, dose adjustment is required).

Effects on the liver

It is recommended to carry out the determination of liver function indices before the start of therapy and 3 months after the start of therapy. Taking rosuvastatin should stop or reduce the dose of the drug if the activity of "hepatic" transaminases in the serum is 3 times higher than VGN.

In patients with hypercholesterolemia due to hypothyroidism or nephritic syndrome, therapy for major diseases should be performed prior to the beginning of treatment with rose vastatinum.

Special populations. Ethnic groups

In the course of pharmacokinetic studies among Mongoloid patients, an increase in the systemic concentration of rosuvastatin was noted in comparison with the indices obtained among patients with Europoids (see the sections "Dosing and Administration" and "Pharmacological properties").

Protease Inhibitors HIV

It is not recommended to use the drug together with HIV protease inhibitors

(see the section "Interaction with other medicinal products").

Lactose

Rosuvastatin should not be taken to patients with rare hereditary intolerance to galactose, a deficiency of lactase and a syndrome of glucose-galactose malabsorption.

Iterstitial lung disease

With the use of some statins, especially for a long time, there have been reports of single cases of Iterstitial lung disease. Manifestations of the disease can be shortness of breath, unproductive cough and deterioration in overall health (weakness, weight loss and fever). If suspected of chronic pulmonary disease, statin therapy should be discontinued.

Diabetes mellitus type 2

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

Effect on the ability to drive transp. cf. and fur:There have been no studies on the effect of rosuvastatin on the ability to drive a vehicle and use mechanisms. Care should be taken when driving a motor vehicle or work that requires a high concentration of attention and speed of psychomotor reactions (dizziness may occur during therapy).

Form release / dosage:Tablets, film-coated 10 mg, 20 mg, 40 mg.

Packaging:For 10. 14 or 15 tablets in a contour mesh box made of a polyvinylchloride film and aluminum foil. By 1, 2, 3, 4, 5, 6, 8 or 9 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003025

Date of registration:04.06.2015

Date of cancellation:2020-06-04

The owner of the registration certificate:IZVARINO PHARMA, LLC IZVARINO PHARMA, LLC Russia

Manufacturer: & nbsp

IZVARINO PHARMA, LLC Russia

Information update date: & nbsp23.05.2016

Illustrated instructions

Instructions

Rosuvastatin (Rozuvastatine)