Rosacea 10 mg tablets 90

Rosuvastatin Instructions for use

Composition

active ingredient: rosuvastatin; 1 tablet contains rosuvastatin (in the form of rosuvastatin calcium salt) 10 mg or 20 mg or 40 mg;
auxiliary substances: lactose, microcrystalline cellulose, croscarmellose sodium, silicon dioxide colloidal, magnesium stearate, gipermellose 2910/5, macrogol 6000, titanium dioxide (E 171), talc, iron oxide red (E 172).

Dosage form

Tablets coated.

Basic physical and chemical properties:

tablets of 10 mg oval biconvex tablets coated, light pink with a scratch;

tablets of 20 mg oval biconvex pill capsules, pink

Tablets of 40 mg oval biconvex pill capsules, dark pink.

Pharmacological group

Hypilipidemic means . HMG-CoA reductase inhibitors. Code АТХ С10А А07.

Pharmacological properties

Pharmacodynamics.

Rosevastatin is a selective competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaric anoenzymes A into mevalonate, a cholesterol precursor. The main place of action of rosuvastatin is the liver where cholesterol synthesis (CHO) occurs and catabolism of low density lipoprotein (LDL).

Rosevastatin increases the number of hepatic LDL receptors on the cell surface, increasing the capture and catabolism of LDL, which in turn leads to the inhibition of the synthesis of very low density lipoprotein (LPONP), thus reducing the total amount of LDL and LDLP.

Rosevastatin reduces the increased amount of LDL cholesterol (LDL cholesterol), total cholesterol and triglycerides (TG), and somewhat increases the amount of high-density lipoprotein cholesterol (HDL-HDL). It reduces the amount of apolipoprotein B (ApoV), X-LDH, X-LPONP, TG-LPONP, and somewhat increases the level of apolipoprotein A-I (ApoA-I), decreases the ratio of LDL / X-HDL cholesterol, total cholesterol / HDL-HDL and HDL-HDL / HDL-HDL and the ratio of ApoV / ApoA-i.

The therapeutic effect is manifested within 1 week after the start of therapy with rosuvastatin, after 2 weeks of treatment the effect is achieved 90% of the maximum possible effect. The maximal effect is usually achieved after 4 weeks and then continues continuously.

Pharmacokinetics.
Suction and distribution

The maximum concentration of rosuvastatin in the blood plasma is reached after 5 hours after ingestion. Bioavailability is approximately 20%. Rosevastatin accumulates in the liver. The volume of its distribution is approximately 134 liters.Almost 90% of rosuvastatin binds to plasma proteins, mainly albumin.

Metabolism
Rosevastatin is subjected to a limited metabolism (about 10%). Rosevastatin is a non-profile substrate for metabolism by cytochrome P450 enzymes. The main isoenzymic involved in the metabolism of rosuvastatin is CYP2C9. The enzymes CYP2C19, CYP3A4 and CYP2D6 take less active part in the metabolism. The major detected metabolites of rosuvastatin are N-dysmethyl and lactone metabolites. N-dysmethyl is approximately 50% less active than rosuvastatin, lactone metabolites are pharmacologically inactive.

Conclusion
Approximately 90% of the dose of rosuvastatin is excreted unchanged with faeces (including absorbed and unabsorbed rosuvastatin). The other part is excreted in the urine. The half-life is about 19 hours. The half-life does not change when the dose is increased. The average geometric clearance is about 50 l / h (coefficient of variation 21.7%). As with other HMG-CoA reductase inhibitors, cholesterol transporter plays a role in the hepatic seizure of rosuvastatin, which plays an important role in hepatic elimination of rosuvastatin.

Linearity
The systemic exposure of rosuvastatin increases proportionally to the dose. When taking several daily doses, the pharmacokinetic parameters do not change.

Special populations of patients
Age and sex

There is no clinically significant effect of age and gender on the pharmacokinetics of rosuvastatin in adults.

Ethnic groups

The representatives of the Asian peoples (Japanese, Chinese, Filipino, Vietnamese and Korean), the control panel (the area under the "concentration-time" curve) and the C max are approximately 2 times larger than that of the representatives of the European race. Indians showed an increase in the median of PPK and C max by 1.3x. Population pharmacokinetic analysis has revealed that there are no clinically significant differences in pharmacokinetics between representatives of the European and non-neurodetectional races.

Patients with renal insufficiency
In patients with mild or moderate renal impairment, the concentration of rosuvastatin and N-dysmethyl in the plasma does not change significantly. In patients with severe renal insufficiency (creatinine clearance <30 ml / min), the concentration of rosuvastatin in plasma is 3 times higher and the N-dismethyl concentration is 9 times higher than in healthy volunteers. Plasma concentrations of rosuvastatin in patients undergoing hemodialysis were approximately 50% higher than in healthy volunteers.

Patients with hepatic insufficiency
Among patients with varying degrees of hepatic insufficiency, no increase in the half-life of rosuvastatin was observed, if the Child-Pugh score was 7 or lower. However, in two patients with points 8 and 9 in Child-Pugh, an elongation of the half-life was observed at least 2 times. Experience with rosuvastatin in patients with a score above 9 by Child-Pugh is absent.

Indications

Treatment of hypercholesterolemia

Adults, adolescents and children over 10 years of age with primary hypercholesterolemia (type Pa, including heterozygous familial hypercholesterolemia) or mixed dyslipidemia (type IIb) as an addition to the diet, when diet and other non-drug treatments (for example, exercise, weight loss body) is inadequate.

With homozygous familial hypercholesterolemia as an add-on to a diet and other lipid-lowering medications (such as apheresis LDL) or in cases where such treatment is inappropriate.

Prevention of cardiovascular disorders

Prevention of a significant cardiovascular disorder in patients who are estimated to be at high risk for the first case of cardiovascular disease as a complement to the correction of other risk factors.

Contraindications

• Hypersensitivity to roseuvastatin or to auxiliary substances;
• liver disease in the active phase, including persistent elevation of serum transaminases of unknown etiology and the level of any transaminase more than 3 times higher than the upper limit of the norm (VMN)
• severe renal impairment (creatinine clearance <30 ml / min);
• myopathy;
• simultaneous administration of cyclosporine;
• pregnancy and breastfeeding period. Contraindicated in reproductive age, not using appropriate contraceptives.

A dose of 40 mg is contraindicated in patients with factors contributing to the development of myopathy / rhabdomyolysis. These factors include:

• moderate renal impairment (creatinine clearance <60 ml / min);
• hypothyroidism
• presence in an individual or family history of hereditary muscular diseases;
• presence in the history of myotoxicity caused by other HMG-CoA reductase inhibitors or fibrates;
• alcohol abuse;
• situations that can lead to an increase in the level of the drug in the blood plasma
• belonging to the Mongoloid race;
• simultaneous application of fibers.

Interaction with other drugs and other types of interactions

Effect of concomitant medications on rosuvastatin

Inhibitors of transport proteins

Rosa-vatatin is a substrate for some transport proteins, including the hepatic transfusion receptor OATP1B1 and the BCRP fluorescence conveyor. Concomitant use of a drug with drugs that depresses these transport proteins may result in increased concentrations of risuvastatin in plasma and an increased risk of myopathy (see sections "Method of administration and dose", "Special features", "Interaction with other drugs and other mechanisms" ", Table 2).

Ciclosporin

During the co-administration of the drug and cyclosporine, the AUC of roseuvastatin was on average about 7 times higher than that observed in healthy volunteers (see Table 2). The drug is contraindicated in patients who receive cyclosporin at the same time (see Section "Contraindications").

Simultaneous application did not affect the concentration of cyclosporin in plasma.

Protease inhibitors

Although the exact 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 pharmacokinetic study, the simultaneous use of 10 mg of rosuvastatin and a combined medication containing two protease inhibitors (300 mg of atazanavir / 100 mg of ritonavir) in healthy volunteers was accompanied by an increase in AUC and C max of rosuvastatin by about 3 and 7 times, respectively. The simultaneous application of the drug and some combinations of protease inhibitors is possible after careful consideration of the dose adjustment of the drug based on the expected increase in the exposure of rosuvastatin (see sections "Method of administration and dose", "Application features", "Interaction with other drugs and other types of interactions" table 2).

Gemfibrozil and other hypolipidemic agents

Simultaneous administration of the product and gemfibrozil allowed 2 times the growth of AUC and C max of rosuvastatin (see Section "Special Features").

Based on data from special studies, pharmacokinetic-significant interaction with fenofibrate is not expected, however, a pharmacodynamic interaction is possible. Gemfibrozil, phenofibrate, other fibrates and hypolipidemic doses (> 1 g / day) of niacin (nicotinic acid) increase the risk of myopathy when co-administered with HMG-CoA inhibitors, probably due to the fact that they can cause myopathy, when they are apply separately. A dose of 40 mg is contraindicated when using fibrates at the same time (see sections "Contraindications" and "Special features"). Such patients should also initiate therapy at a dose of 5 mg.

Ezetimib

Simultaneous administration of 10 mg and 10 mg ezetimibe to patients with hypercholesterolemia resulted in a 1.2-fold increase in rosuvastatin AUC (Table 2). The pharmacodynamic interaction between the drug and ezetimib can not be ruled out, which may lead to undesirable effects (see Section "Application Features").

Antacids

Simultaneous administration of the drug from suspension of antacids containing aluminum hydroxide or magnesium reduced the plasma concentrations of rosuvastatin by 50%. This effect was less pronounced in the case of the use of antacids at 2 hours after the drug. The clinical significance of this interaction was not studied.

Erythromycin

Simultaneous administration of the drug and erythromycin reduced the AUC of rosuvastatin by 20% and C max by 30%.This interaction may be due to increased bowel peristalsis due to the action of erythromycin.

Enzymes of cytochrome P450

The results of in vitro and in vivo studies indicate that rosuvastatin is not inhibited and does not stimulate isoenzymes of cytochrome P450. In addition, rosuvastatin is a weak substrate of these isoenzymes. Thus, interaction with drugs as a result of 450 mediated metabolism is not expected. There were no clinically relevant interactions between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4) or ketoconazole (an inhibitor of CYP2A6 and CYP3A4).

Interactions requiring dose adjustment of rosuvastatin

If the drug is to be used with other drugs that can increase the exposure of rosuvastatin, the dose of the drug should be adjusted. If the exposure (AUC) is expected to increase by about 2 or more times, the drug should be started at a dose of 5 mg once a day. The maximum daily dose of the preparation should be adjusted in such a way that the expected exposure of rosuvastatin does not exceed the exposure, it is noted at a dose of 40 mg / day without the use of drugs that interact with the drug; for example, when administered with gemfibrozil, the dose will be 20 mg (increase in exposure by 1.9), with ritonavir / atazanavir - 10 mg (increase by 3.1 times), with concomitant use with cyclosporine - 5 mg (increase in 7.1 times).

Table 2

Effect of concomitant drugs on exposure to rosuvastatin (AUC, in order of decreasing magnitude) according to published clinical trials

Dosage regimen of the drug, interacts	Dosage regimen of rosuvastatin	Changes in rosuvastatin AUC *
Ciclosporin from 75 mg twice a day to 200 mg 2 times a day for 6 months	10 mg once daily for 10 days	↑ 7.1 times
Atazanavir 300 mg / ritonavir 100 mg once daily, 8 days	10 mg, once	↑ 3.1 times
Symmevirin 150 mg once daily for 7 days	10 mg, once	↑ 2.8 times
Lopinavir 400 mg / ritonavir 100 mg 2 times a day, 17 days	20 mg once daily, 7 days	↑ 2.1 times
Gemfibrozil 600 mg twice a day, 7 days	80 mg, once	↑ 1.9 times
Eltromobopak 75 mg once daily for 5 days	10 mg, once	↑ 1.6 times
Darunavir 600 mg / ritonavir 100 mg 2 times a day, 7 days	10 mg once daily for 7 days	↑ 1.5 times
Tipranavir 500 mg / ritonavir 200 mg 2 times a day, 11 days	10 mg, once	↑ 1.4 times
Dronedarone 400 mg twice a day	not known	↑ 1.4 times
Itraconazole 200 mg once daily for 5 days	10 mg, once	↑ 1.4 times **
Ezetimib 10 mg once daily, 14 days	10 mg once daily for 14 days	↑ 1.2 times **
Phasamprenavir 700 mg / ritonavir 100 mg 2 times a day, 8 days	10 mg, once	↔
But glitazar 0.3 mg, 7 days	40 mg, 7 days	↔
Silymarin 140 mg 3 times a day, 5 days	10 mg, once	↔
Fenofibrate 67 mg 3 times a day, 7 days	10 mg, 7 days	↔
Rifampicin 450 mg once daily for 7 days	20 mg, once	↔
Ketoconazole 200 mg twice a day, 7 days	80 mg, once	↔
Fluconazole 200 mg once daily for 11 days	80 mg, once	↔
Erythromycin 500 mg 4 times a day, 7 days	80 mg, once	↓ 20%
Baikalin 50 mg 3 times a day, 14 days	20 mg, once	↓ 47%

* The data presented as a change in x times is the ratio between the use of rosuvastatin in combination and separately.The data presented in the form of% change is% of the difference in performance when using rosuvastatin alone.

The magnification is indicated by ↑, no change ↔, decrease - ↓.

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

Effect of rosuvastatin on concomitant medications

Antagonists of vitamin K.

As with other HMG-CoA reductase inhibitors, an increase in the international normalized ratio (MHC) is possible at the start of the drug application or when its dose is increased in patients receiving concomitant vitamin K antagonists (eg warfarin or other coumarin anticoagulants). Cancellation of the drug or a decrease in its dose can lead to a decrease in the MES. In such cases, the proper monitoring of the Ministry of Emergencies is desirable.

Oral Contraceptives / Hormone Replacement Therapy (HRT)

Concurrent administration of the drug and oral contraceptives resulted in an increase in AUC of ethinyl estradiol and norgestrel at 26% and 34% respectively. Such an increase in plasma levels of blood should be taken into account when choosing a dose of oral contraceptives. There is no data on the pharmacokinetics of drugs in patients receiving concomitant medication and HRT, so this effect can not be ruled out. However, the combination was widely used by women in clinical trials and was well tolerated.

Other medicines

According to special studies, the interaction of a clinically meaningful interaction with digoxin is not expected.

Lopinavir / ritonavir

In a pharmacological study, the simultaneous use of the drug and a combination product containing two protease inhibitors (lopinavir 400 mg / ritonavir 100 mg) in healthy volunteers was associated with approximately two and five times the increase in equilibrium AUC (0-24) and C max for rosuvastatin consistent. The interaction between rosuvastatin and other protease inhibitors has not been studied.

Fusidic acid

The risk of developing myopathy, including rhabdomyolysis, may increase with the simultaneous administration of fusidic acid systemic agents and statins. The mechanism of this interaction (or this pharmacodynamic interaction, or pharmacokinetic interaction, or both forms of interaction at the same time) is not yet known. There were reports of cases of rhabdomyolysis (including fatal outcome) in patients who received such a combination of drugs.

If the use of the fusidic acid systemic agent is necessary, the treatment with the drug should be discontinued for the entire period of treatment of fusidic acid.

Where are you

Study interaction conducted in Adults Only patients. Degree of interaction in children Unknown.

Application features

Effect on kidney

Proteinuria, obnaruzhennaya as a result of analysis on a test stripes and preymuschestvenno tubular origin, nablyudalas in patsyentov, lechyvshyhsya High doses of drugs, including volume of 40 mg, and in Most cases bыla vremennoy or prerыvystoy. Proteinuria us bыla predvestnykom or acute kidney disease prohressyruyuschey (see. Section "Side reactions"). The frequency of messages Choose sereznыh phenomenon co storony postmarketynhovыh in kidney research in the Application dozы Above 40 mg. In patsyentov, prynymayuschyh drug dose to 40 mg, in the course of regular observation sleduet Provera kidney function.

Effect on muscles skeletnuyu

Co storony muskulaturы bones, for example myalgia, myopathy and rarely rabdomyolyz nablyudalys in patsyentov, prynymavshyh lyubыh drug in doses, especially more than 20 mg. Edynychnыe cases rabdomyolyza otmechalys with Application эzetymyba in kombynatsyy with inhibitors of HMG-CoA reductase. Ability impossible ysklyuchat farmakodynamycheskoho interaction (see. Section "Interaction with the second lekarstvennыmy funds and others types vzaymodeystvyy"), and after such kombynatsyyu sleduet Apply with caution.

As and when the second ynhybytorov Application of HMG-CoA reductase, the frequency of messages Choose rabdomyolyza cases, associated with drug primeneniem in the post-marketing period bыla Above dose at 40 mg. Ymeyutsya messages rarely cases of necrotizing myopathy ymmunooposredovannыh, Clinical manifested stoykoy proksyzmalnoyu mыshechnoy slabostyu Increase urovnja and serum CPK, IN TIME of treatment or after prekraschenyya of treatment with statins, rosuvastatin vkljuchaja. In this sluchae Can potrebovatsya Additional neyromыshechnыe and serological research, of treatment immunosuppressive drugs.

Level of CPK

Level of CPK (UK) It should not yzmeryat after znachytelnыh fyzycheskyh nahruzok or availability at vozmozhnыh alternatyvnыh reasons Increase UK, mogut zatrudnyat interpretation of results. If yshodnыe Levels Significantly UK povыshenы (> 5 times upper boundaries Above norm) in 5-7 days techenye neobhodimo Set povtornыy analysis, Avto confirm results. If re-analysis Results podtverzhdayut, Primary something meaning something more than UK 5 times prevыshaet VNM, the Start Application drug It should not.

Before the beginning of treatment

Rosuvastatin, and global Global ynhybytorov As HMG-CoA reductase, sleduet with caution assign patsyentam co sklonnostyu for myopathy / rabdomyolyza. K factor of the line include:

• violation kidney function
• hypothyroidism
• The presence of family or personally in anamneze nasledstvennыh muscle diseases;
• The presence in anamneze myotoksychnosty on fone Application ynhybytorov second HMG-CoA reductase or fibratov;
• zloupotreblenye alcohol;
• vozrast> 70 years;
• situation, kotoryya mogut Increase urovnja for lead drug in plasma (cm. divisions "Method and Application dozы", "Interaction with the second lekarstvennыmy funds and others types vzaymodeystvyy" and "Pharmacokinetics");
• Application simultaneous fibratov.

In such patsyentov svjazana Treatment with risk Nuzhny otsenyvat, sravnyvaya with ozhydaemoy polzoy; Clinical MONITORING also recommended. If the Initial Levels Significantly UK povыshenы (> 5 times upper boundaries Above norm), the Start Treatment It should not.

In the period of treatment

It should ask Patsyentov nemedlenno Report mыshechnoy pain, weakness or cramps neyzvestnoy aetiology, especially îíè If soprovozhdayutsya nedomohanyem or lyhoradkoy. In such patsyentov Nuzhny yzmeryat Level CPK. Application drug sleduet prekratyt, Level If CPK Significantly povыshenы (> 5 x upper boundaries once Above norm) If symptoms or co storony Heavy muscle discomfort and vыzыvayut ezhednevnыy (Even If Level CPK ≤ 5 x ULN). In cases yscheznovenyya symptomov Normalize and Restore can be urovnja CPK drug therapy or alternatyvnыm inhibitor of HMG-CoA reductase in a pod maleyshey dose tschatelnыm observation. Regularly Provera Level CPK in asymptomatic patsyentov not required. Very rarely was reported cases of necrotizing myopathy ymmunooposredovannыh (YONM) t Time or after therapy with statins,including a Tom rosuvastatin. Clinical manifestations YONM proximal muscle weakness javljaetsja and Increase urovnja whey CPK in the blood, something persists Even after otmenы statins.

In Clinical Studies It would not polucheno dokazatelstv povыshennoho Impact on skeletnuyu muscles in nebolshoho Quantity patsyentov, kotoryya prynymaly and soputstvuyuschye drugs. However Increase frequency myositis and myopathy otmechalos in patsyentov, prynymavshyh others ynhybytorы HMG-CoA reductase Together with proyzvodnыmy fybroevoy acid, the volume number hemfybrozylom, cyclosporine, nykotynovoy kyslotoy, azolnыmy antifungal agents, inhibitors and macrolide antibiotics proteazy. Hemfybrozyl povыshaet risk of myopathy when simultaneously with nekotorыmy Application inhibitor of HMG-CoA. Therefore Apply The combination drug is not recommended with hemfybrozylom. Changed favor dalneysheho urovnja lypydov Application with drugs in kombynatsyy with fybratamy or niacin Nuzhny tschatelno vzveshyvat compared to potentsyalnыmy dashessvyazannыmy with primeneniem such kombynatsyy. A dose of 40 mg contraindicated while simultaneously fibratov Application (cm. Sections "Interaction with the second lekarstvennыmy funds and others types vzaymodeystvyy" and "Side reactions").

Препарат не следует применять пациентам с острыми, серьезными состояниями, свидетельствующие о миопатии или возможность развития почечной недостаточности вследствие рабдомиолиза (таких как сепсис, гипотензия, значительное хирургическое вмешательство, травма, тяжелые метаболические, эндокринные и электролитические расстройства или неконтролируемые судороги).

Влияние на печень

Как и другие ингибиторы ГМГ-КоА-редуктазы, препарат следует с осторожностью применять пациентам, которые злоупотребляют алкоголем и / или имеющим в анамнезе заболевания печени.

Рекомендуется проводить биохимические показатели функции печени перед началом лечения и через 3 месяца спустя. Применение препарата следует прекратить или уменьшить дозу, если уровень трансаминаз в сыворотке крови более чем в 3 раза превышает верхнюю границу нормы. Частота сообщений о серьезных явления со стороны печени (преимущественно о повышении уровня трансаминаз печени) в пострегистрационный период была выше при применении дозы 40 мг.

У пациентов с вторичной гиперхолестеринемией, обусловленной гипотиреозом или нефротическим синдромом, следует сначала вылечить основную болезнь, прежде чем начинать терапию препаратом.

В пострегистрационных периоде изредка сообщалось о летальных или нелетальных случаи печеночной недостаточности у пациентов, принимавших статины, в том числе розувастатин. Если на фоне лечения развивается серьезное поражение печени с клинической симптоматикой и / или гипербилирубинемией или желтухой, следует немедленно прекратить прием препарата. Если других причин не обнаружено, не следует возобновлять лечение препаратом.

Раса

Studies of pharmacokinetics svydetelstvuyut growing Exposition in patsyentov monholoydnoy rasы prymerno 2 times compared to Europeans. For such patsyentov neobhodyma correction dozы drugs (cm. Sections "Method and Application dozы", "Contraindications" and "Pharmacokinetics"). For patsyentov azyatskoy rasы nachalnaya dose rosuvastatin 5 mg dolzhna bыt. Concentration at peak times rosuvastatin plasma bыla zamechena in azyatskyh patsyentov (see. Section "Application Features" and "Pharmacokinetics"). It should Accept WARNING t vozrosshuyu systemnuyu Exposition at patsyentov Treatment monholoydnoy rasы in kotorыh giperholesterinemija not kontrolyruetsya adequate doses up to 20 mg.

Ynhybytorы proteazy

Systemnaya Exposition peak times for nablyudalas rosuvastatin in persons, rosuvastatin prynymavshyh soputstvuyuschee with razlychnыmy inhibitor in proteazy The combination with rytonavyrom. It should obdumat As such favor Reduction urovnja lypydov with pomoshchju drugs in patsyentov with HIV, kotoryya poluchayut ynhybytorы proteazy well and Increase Ability rosuvastatin concentrations in plasma and in early therapy with rosuvastatin dozы Increase in patsyentov, poluchayuschyh ynhybytorы proteazy. Application with simultaneous drug proteazy inhibitors is not recommended, dose rosuvastatin If not skorrektyrovannыe (see. Section "Method and Application dozы" and "Interaction with the second lekarstvennыmy funds and others types vzaymodeystvyy").

lactose intolerance

Patsyentam s rarely nasledstvennыmy forms of intolerance to galactose, laktazы Lappa deficit or glucose-galactose malabsorption It should not Apply this product.

Ynterstytsyalnaya lung disease

With Application nekotorыh statins, especially with dlytelnom Treatment, ysklyuchytelnыh was reported about cases of interstitial lung disease (see. Section "Side reactions"). K эtoy disease manifestations can be otnesty odыshku, neproduktyvnыy cough and Global uhudshenye STATUS (Fatigue peak times, Reduction Fire-proof compounds fever and pulmonary embolism). In cases podozrenyya on ynterstytsyalnuyu lung disease sleduet prekratyt Application statins.

Saharnыy diabetes

Some facts suggest that statins increase blood glucose levels and in some patients who are at high risk of developing diabetes in the future can cause hyperglycemia at a level that requires proper treatment for diabetes. This threat, however, exceeds the reduction in the risk of vascular disorders in the use of statins, and therefore it should not be grounds for stopping statin therapy. Patients at risk (fasting glucose level 5.6-6.0 mmol / L, BMI> 30 kg / m 2, elevated triglycerides, hypertension) should be assigned both clinical and biochemical control in accordance with national guidelines.

The JUPITER study reported a total incidence of diabetes mellitus of 2.8% in the rosuvastatin group and 2.3% in the placebo group, predominantly in patients with fasting glucose levels of 5.6 to 6.9 mmol / L.

As in other inhibitors of HMG-CoA reductase, the use of rosuvastatin showed an increase in HbA1c and a serum glucose level. In some cases, these values may exceed the threshold for the diagnosis of diabetes mellitus, especially in patients at high risk of developing diabetes.

In clinical studies it was shown that rosuvastatin as monotherapy does not cause a decrease in the baseline plasma cortisol concentration and does not affect the adrenal reserve. Care must be taken when using the drug and other drugs that can reduce the level or activity of endogenous steroid hormones, for example ketoconazole, spironolactone and cimetidine.

The drug should not be used concomitantly with fusidic acid preparations of systemic action or within 7 days after discontinuation of fusidic acid treatment. In patients who require systemic action of fusidic acid, statin therapy should be suspended for the entire treatment of fusidic acid. There have been reports of cases of rhabdomyolysis (including fatal) in patients who received fusidic acid and statin preparations simultaneously (see Section "Interaction with Other Drugs and Other Interactions"). The patient should be notified that if symptoms such as muscle weakness, pain or tenderness in the muscles appear, medical attention should be sought immediately.

Can statin therapy bыt vozobnovlena within 7 days after pryema posledney dozы drug fuzydovoy acid.

In ysklyuchytelnыh cases, when drug therapy dlytelnaya fuzydovoy acid javljaetsja neobhodymыm systemic action, for example, of treatment for diseases tyazhelыh ynfektsyonnыh, Need Application and simultaneously fuzydovoy acid dolzhna rassmatryvatsya in kazhdogo sluchae separately and osuschestvlyatsya pod tschatelnыm medical observation.

Where are you

Comments linear growth (growth), Fire-proof compounds PE YMT (index Fire-proof compounds PE) and vtorychnыh sozrevanyya sexual performance by Tanner in age from 10 to 17 years, kotoryya prynymaly rosuvastatin, restricted period prodolzhytelnostyu 1 hour. After 52 weeks of treatment yssleduemoho nykakoho Effect on growth, Massa PE or Sexual YMT sozrevanye obnaruzheno was not. (See. Section "Farmakolohycheskye"). Clinical Application Experience of research of the drug in children and pydlykam restricted, and dolhovremennыe эffektы Application rosuvastatin (> 1 hour) on Sexual sozrevanye neyzvestnы.

In a clinical study in children and adolescents who took rosuvastatin for 52 weeks, an increase in QC was> 10 times higher than BMD and muscle symptoms after exercise or increased physical activity were observed more frequently than those seen in adults (see Section "Adverse Events" reactions ").

Use during pregnancy or breastfeeding.

The drug is contraindicated during pregnancy and breastfeeding.

Women of childbearing age need to use appropriate contraception.

Since cholesterol and other cholesterol biosynthesis products play a significant role in fetal development, the potential risk of HMG-CoA reductase depression is greater than the benefits of using the drug during pregnancy. Animal reproductive toxicity data are limited. If the patient becomes pregnant during treatment, treatment should be stopped immediately.

As another drug of this class penetrates breast milk and given that HMG-CoA reductase inhibitors can cause serious adverse reactions in infants, women who need treatment should be advised to abstain from breast-feeding. There is no data on the penetration of the drug into breast milk in humans (see section "Contraindications").

Ability to influence the speed of reaction when driving motor vehicles or other mechanisms

Taking into account the pharmacodynamic properties of rosuvastatin, its effect on the ability to drive vehicles and to work with mechanisms is unlikely. When driving vehicles or working with other mechanisms, it should be kept in mind that dizziness may develop during treatment.

Method of administration and dose

Before starting treatment, the patient should be transferred to a standard diet, lowering the level of cholesterol, which he should adhere to and throughout the treatment. The dose should be selected individually, depending on the purpose of the therapy and the patient's response to the treatment, based on the current recommendations.

Rosevastatin can be taken at any time of the day, regardless of food intake.

Treatment of hypercholesterolemia

The recommended initial dose for patients not previously treated with statins or transmitted by the administration of another HMG-CoA reductase inhibitor is 5 or 10 mg per day. A dose of 5 mg can be obtained by dividing the tablet 10 mg in half along the fault line.

When choosing an initial dose, the cholesterol level and the risk of cardiovascular complications in a particular patient should be taken into account, as well as the potential risk of side effects (see sections "Peculiarities of use" and "Adverse reactions"). If necessary, the dose can be increased to the next level no earlier than in 4 weeks. Since 40 mg in the treatment of lower doses, the risk of developing adverse reactions is higher (see Section "Adverse Reactions"), bringing the dose to a maximum level of 40 mg is possible only after 4 weeks of treatment and only in patients with severe hypercholesterolemia with high the risk of developing cardiovascular complications (especially in patients with familial hypercholesterolemia) who have not achieved the desired result at 20 mg and who will be under close medical supervision. At the beginning of the dose of 40 mg, observation of specialists is recommended.

Prevention of cardiovascular disorders

The recommended daily dose is 20 mg. For patients with hypercholesterolemia, a standard definition of lipid levels should be performed and compliance with the dosage recommendations for the treatment of hypercholesterolemia.

Use in elderly patients

For patients over 70 years of age, an initial dose of 5 mg is recommended (see section "Special Features"). No other dose correction is required in connection with age.

Application to children

The usual dose for children with heterozygous familial hypercholesterolemia is 5-20 mg once daily orally. To achieve therapeutic effect, the dose should be properly titrated. The safety and efficacy of doses exceeding 20 mg have not been studied in this population. Pills of 40 mg do not apply to children.

Dosage for patients with impaired kidney function

For patients with renal insufficiency, a mild dose adjustment is not required. Patients with moderate renal insufficiency (creatinine clearance <60 ml / min) should start treatment at a dose of 5 mg per day. A dose of 40 mg is contraindicated in patients with moderate renal insufficiency. Rosevastatin in any dose is contraindicated in patients with severe renal insufficiency (see Sections "Contraindications" and "Pharmacological properties").

Dosage for patients with impaired liver function

Patients with a score of 7 and below on the Child-Pugh scale did not show an increase in systemic exposure to rosuvastatin. However, in patients with 8 and 9 points in Child-Pugh system exposure increased (see Section "Pharmacological Properties"). In these patients, a kidney function test should be performed (see Section "Application Features"). The experience of using the drug in patients with hepatic failure with a score higher than 9 on the Child-Pugh scale is absent. Rosevastatin is contraindicated in patients with liver disease in the active phase (see Section "Contraindications").

Race
Patients in the Mongoloid race had an increased systemic exposure to the drug. The recommended starting dose for such patients is 5 mg. The 40 mg dose is contraindicated and the maximum daily dose is 20 mg.

Dosage for patients with a tendency to develop myopathy
The recommended initial dose for patients with a tendency to develop myopathy is 5 mg.

A dose of 40 mg is contraindicated in some of these patients. The maximum daily dose is 20 mg.

Genetic polymorphism

The genotypes SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA compared to the genotypes SLCO1B1 c.521TT and ABCG2 c.421CC associated with risuvastatin exposure (AUC). For patients with genotypes c.521CC or c.421AA, the maximum recommended daily dose of rosuvastatin is 20 mg.

Rosevastatin is a substrate for various transport proteins (eg, OATP1B1 and BCRP). The risk of myopathy (including rhabdomyolysis) is increased when concomitant use of rosuvastatin with certain drugs that can increase the plasma concentrations of risuvastatin through interaction with these transport proteins (eg, cyclosporine and some protease inhibitors, including combinations of ritonavir with atnazavir, lopinavir and / or tipranavir) . If possible, consideration should be given to alternative treatment and, if necessary, temporarily discontinue treatment with rosuvastatin. In situations where the simultaneous administration of these medicinal products with rosuvastatin is not possible, we must weigh all the benefits and risks of concomitant treatment and carefully select the dose of rosuvastatin.

Where are you

It is not recommended to use rosuvastatin for children under 10 years of age.
The influence of rosuvastatin on linear growth (height), body weight, BMI (body mass index), and the development of secondary Tanner characteristics on the Tanner scale aged 10-17 years were evaluated for only one year. After 52 weeks of application of the study drug, no effect on growth, body weight, BMI or sexual development was detected.

Overdose

There is no specific overdose treatment. Treatment should be symptomatic, supportive measures should be taken if necessary. It is necessary to monitor the function of the liver and the levels of KFK. The benefit of hemodialysis is unlikely.

Adverse reactions

Undesirable effects are noted with the use of the drug, usually light and temporary.

Undesirable reactions are classified by frequency and system organ classes.

Frequency side reactions are distributed as follows: common (≥1 / 100 and <1/10), infrequent (≥1 / 1000 and <1/100), rarely (≥1 / 10000 and <1/1000), very rarely ( <1 / 10,000), unknown frequency (can not be estimated from the available data).

Table 3

System organ class	often	not often	rarely	Very rarely	frequency is unknown
From the blood and lymphatic system			Thrombocyte-singing
From the side of the immune system			Hypersensitivity reactions, including angioneurotic edema
endocrine disorders	diabetes mellitus
mental disorders					depression
From the nervous system	Headache, dizziness			Polyneuropathy, memory loss	Peripheral neuropathy, sleep disorders (including insomnia and nightmares)
On the part of the respiratory system, chest and mediastinum					Cough, shortness of breath
From the gastrointestinal tract	Constipation, nausea, abdominal pain		pancreatitis		diarrhea
From the digestive system			Increased levels of hepatic transaminases	Jaundice, hepatitis
From the skin and subcutaneous tissue		Itching, rash, urticaria			Stevens-Johnson syndrome, toxic epidermal necrolysis
From the skeletal muscles and connective tissue	myalgias		Myopathy (including myositis), rhabdomyolysis	arthralgia	From the side of the tendons, sometimes complicated by ruptures, immuno-occidental necrotizing myopathy
From the kidneys and the urinary system				hematuria
From the reproductive system and the mammary glands				gynecomastia
general disorders	asthenia				swelling

¹ Frequency depends on the presence of risk factors (fasting glucose ≥ 5.6 mmol / l, BMI> 30 kg / m 2, elevated triglyceride levels, history of arterial hypertension).

As with other HMG-CoA inhibitors, the incidence of adverse reactions tends to depend on the dose.

Influence on the kidneys

Proteinuria, found as a result of the analysis by test strips and predominantly tubular origin, was observed in patients receiving the drug. Changes in urine protein content from zero or trace amounts to ++ or higher were observed in <1% of patients at some time points during the use of the drug at doses of 10 and 20 mg in about 3% at a dose of 40 mg. A slight increase in the frequency of changes in the content from zero or traces to the value of + was observed at a dose of 20 mg. In most cases proteinuria decreased or disappeared spontaneously with continued therapy. According to clinical studies and postmarketing observations, there is currently no cause-and-effect relationship between proteinuria and acute or progressive kidney disease.

On the background of the use of the drug noted cases of hematuria; according to clinical studies, its frequency is insignificant.

Influence on skeletal muscle

Musculoskeletal disorders, such as myalgia, myopathy (including myositis), and occasionally rhabdomyolysis with or without acute renal failure have been noted with the use of any dosage of rosuvastatin, especially at doses> 20 mg.

Patients taking rosuvastatin had a dose-dependent increase in CK levels; in most cases the phenomenon was weak, asymptomatic and temporary. If the KFK level is elevated (> 5 times the upper limit of the normal range), treatment should be discontinued (see section "Application Features").

Influence on the liver

As with other HMG-CoA reductase inhibitors, a small proportion of patients taking rosuvastatin had dose-dependent elevations in transaminases; in most cases the phenomenon was weak, asymptomatic and temporary. The use of rosuvastatin also indicated an increase in HbA1c levels.

On the background of the use of certain statins, there were side effects:

sexual dysfunction;

individual cases of interstitial lung disease, especially with long-term use (see section "Peculiarities of application").

Frequency of reports of rhabdomyolysis, serious kidney and liver disorders (mainly increased liver transaminases) is greater when used in a dose of 40 mg.

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

Occasionally, during the post-stroke period, violations of cognitive function (eg, deterioration of memory, forgetfulness, amnesia, memory impairment, confusion of consciousness) that are associated with the use of statins have been reported. Such cognitive problems have been reported in connection with all statins. The phenomena reported in the messages are usually mild and occur after the abolition of statins, and they have different time to the occurrence of symptoms (from 1 day to years) and to the disappearance of symptoms (median - 3 weeks).

Where are you

The elevation of the KFK level> 10 times the upper limit of the norm and the symptoms of the muscles after exercise or increased physical activity were observed more frequently in a 52-week clinical trial involving children and adolescents compared with adults (see Section "Peculiarities of use"). However, the safety profile of rosuvastatin in children and adolescents was similar to that in adults.

Shelf life

2 years

Storage conditions

Store in original packaging in a dry, protected from light, inaccessible to children at a temperature not exceeding 25 ° C.

Packaging

No. 30 (10xZ), No. 90 (10x9): 10 tablets in a blister, 3 or 9 blister cards in a cardboard box.

Vacation category

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