Roxera 40 mg tablets №30

Author Ольга Кияница

2017-05-11

Amount in a package 30
Product form Pills
Manufacturer KRKA (Slovenia)
Registration certificate UA/11743/01/04
The main medicament Roxer
morion code 142236

Roxera (instructions for use)

Composition

active ingredient: 1 film coated tablet contains 5 mg or 10 mg or 15 mg or 20 mg or 30 mg or 40 mg rosuvastatin (as rosuvastatin calcium)

auxiliary substances: microcrystalline cellulose, lactose, crospovidone, silicon dioxide colloid, magnesium stearate

film coat: methacrylate copolymer, macrogol 6000, titanium dioxide (E 171), lactose.

Dosage form.

Tablets coated with a film coat.

Basic physical and chemical properties:

  • 5 mg of white color round, several biconvex, coated film coated tablets with beveled edges and engraved "5" on one side;
  • 10 mg of white color round, several biconvex, film-coated tablet with beveled edges and engraving "10" on one side.
  • 15 mg of white color round, several biconvex, film-coated tablets of beveled edges and engraved "15" on one side.
  • 20 mg of white round, round film coated tablets with a bevelled edge;
  • 30 mg of white color, biconvex, film-coated tablets in the form of a capsule with an incision on both sides;
  • 40 mg of white color, biconvex, film-coated tablets in capsule form.

Pharmacological group

Hypilipidemic means. HMG-CoA reductase inhibitors.

Code ATX C10A A07.

Pharmacological properties

Pharmacodynamics.

Rosevastatin reduces elevated concentrations of LDL cholesterol, total cholesterol and triglycerides, and increases cholesterol concentrations of high density lipoprotein (HDL). It also significantly reduces the concentration of apolipoprotein B, low density lipoprotein cholesterol (LDL), cholesterol LPONP, triglycerides of LPONP, and increases the concentration of apolipoprotein A-I. The dosage of the Roxer also reduces the ratio of LDL cholesterol / cholesterol HDL cholesterol, total cholesterol / cholesterol HDL and cholesterol LDL cholesterol / HDL cholesterol, as well as apolipoprotein B / apolipoprotein A-I.

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 maximal effect is usually achieved after 4 weeks and is maintained during treatment.

Pharmacokinetics.

Absorption

The maximum concentrations of rosuvastatin in plasma are reached after 5 hours after oral administration.Bioavailability is approximately 20%.

Distribution

Rosevastatin is extensively converted to the liver, which is the primary center for the synthesis of cholesterol and clearance of LDL cholesterol. The dosage of rosuvastatin is approximately 134 liters. Approximately 90% of rosuvastatin binds to plasma proteins, mainly albumin.

Metabolism

Rosevastatin undergoes a limited metabolism (approximately 10%). In vitro metabolism studies using human hepatocytes indicate that rosuvastatin is only subjected to a minimal metabolism based on 450, and this metabolism is not clinically important. CYP2C9 was the major isoenzymic involved in the metabolism, with 2C19, ZA4 and 2D6, which were less involved. The major metabolites are metabolites N-desmethyl and lactone. The metabolite N-desmethyl is approximately 50% less active than rosuvastatin, the lactone form is considered to be clinically inactive. Rosevastatin has more than 90% inhibitory activity in relation to HMG-CoA-reductase, circulating in the general circulation.

Conclusion

Approximately 90% of the dose of rosuvastatin is excreted unchanged with faeces (consists of an absorbed and non-adsorbed active substance), and the remainder is excreted in the urine. Approximately 5% is excreted intact with urine.The half-life is about 20 hours. The half-life does not increase with high dosage. The geometric mean clearance from plasma is about 50 liters per hour (coefficient of variation 21.7%). As with other HMG-CoA reductase inhibitors, the seizure of rosuvastatin by the liver is attracted by the OATP-C membrane conveyor. This conveyer is important for the withdrawal of rosuvastatin from the liver.

Linearity

The systemic exposure to rosuvastatin increases in proportion to the increase in dose. There is no change in pharmacokinetic parameters after repeated daily administration.

Groups of patients

Race

Pharmacokinetic studies demonstrate an increase of about 2 times the AUC and C max of roseuvastatin in patients from Asian peoples (Japanese, Chinese, Filipino, Vietnamese, and Korean) compared with patients from the European race;Hindus have an increase of about 1.3 times the mean values of AUC and C max . Pharmacokinetic analysis of a group of patients did not reveal any clinically significant difference in pharmacokinetics between representatives of the European and Negroid race.

Renal failure

In a study involving patients with varying degrees of renal impairment, mild or moderate kidney disease did not affect the concentration of rosuvastatin or N-desemethyl metabolite in plasma. In patients with severe renal impairment (creatinine clearance <30 ml / min) plasma concentration increased 3-fold, and the concentration of metabolite N-desmethyl was 9 times higher than that of healthy volunteers. Concentrations of rosuvastatin in plasma at steady state in patients undergoing hemodialysis sessions were approximately 50% higher than in healthy volunteers.

Hepatic failure

In the study, with the participation of patients with varying degrees of liver function impairment, there was no evidence of an increase in exposures to rosuvastatin in patients with a 7-fold or lower Child-Pugh classification. However, elevated systemic exposure was observed at least 2-fold in two patients with indicators 8 and 9 in the Child-Pugh classification.

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 (eg, 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.

Doses of 5 mg, 10 mg, 15 mg and 20 mg are contraindicated:

  • Patients with a high sensitivity to rosuvastatin or to any inactive ingredient;
  • patients with active liver disease, including unknown etiology, persistent elevation of transaminases in serum and serum transaminase levels more than 3 times the upper limit of the norm;
  • patients with severe renal impairment (creatinine clearance <30 ml / min);
  • patients with myopathy;
  • patients taking cyclosporine in the same way;
  • patients with already existing factors for myotoxic complications;
  • during pregnancy and breastfeeding, as well as women of reproductive age who do not use appropriate contraceptives;
  • children under the age of 10 years.

Doses of 30 mg and 40 mg are contraindicated:

  • Patients with a high sensitivity to rosuvastatin or to any inactive ingredient;
  • patients with active liver disease, including a strange, persistent increase in the level of transaminases in the serum and any increase in transaminases in the serum than 3 times the upper limit of the norm;
  • patients taking cyclosporine in the same way;
  • during pregnancy and breastfeeding and women of reproductive age who do not use appropriate contraceptives;
  • children;
  • patients with myopathy or already existing factors for myopathy / rhabdomyolysis; such factors include: moderate renal impairment (creatinine clearance <60 ml / min); hypothyroidism; presence in the personal or family history of congenital muscle disorders; history of muscle toxicity induced by another HMG-CoA reductase inhibitor or fibrates; alcohol dependence; a situation where there may be an increase in blood plasma levels (eg severe hepatic failure) of Asian origin; simultaneous application of fibers; age more than 70 years.

Interaction with other drugs and other types of interactions

Rosa-vatatin is a substrate for certain transport proteins, including OATP1B1, which provides hepatic transport, and an EFLUS vector of BCRP. Simultaneous administration of Roxers with drugs - inhibitors of these transport proteins can lead to increased concentrations of risutastin in plasma and an increased risk of myopathy.

When it is necessary to apply Roxer together with other medicines that increase exposure to rosuvastatin, the dose of Roxers should be adjusted. It should be initiated at a dose of 5 mg once daily if an increase in exposure (AUC) is expected to be about 2 times or greater. The maximum daily dose of Roxers should be adjusted in such a way that the expected exposure to rosuvastatin does not exceed the concentration, observed when the daily dose 40 mg of Roxers occurs in the absence of interaction with drugs. For example, a dose of 5 mg of Roxers with concomitant use with cyclosporine (an increase in exposure by 7.1), a dose of 10 mg of Roxers when administered concurrently with the combination of ritonavir / atnazavir (an increase of 3.1 times) and a dose of 20 mg of Roxers at the same time with gemfibrozil (increase by 1.9 times).

Antacids

Simultaneous administration of rosuvastatin with a suspension of antacids containing aluminum and magnesium hydroxide results in a 50% decrease in the concentration of rosuvastatin in the blood plasma. This effect was reduced when antacids were taken at 2 hours after rosuvastatin. The clinical significance of this interaction has not been studied.

Fenofibrates, derivatives of fibrous acid

Although no pharmacokinetic interaction was observed between rosuvastatin and fenofibrate, pharmacodynamic interaction may occur. Gemfibrozil, fenofibrate and other fibrous acids, including nicotinic acid, can increase the risk of myopathy when administered concurrently with HMG-CoA reductase inhibitors.

Ciclosporin

In the co-administration of Roxera and cyclosporine, the value of AUC of rosuvastatin was approximately 7 times higher than that observed in healthy volunteers (see Table 2). A rokker is contraindicated in patients who receive cyclosporin (see Section "Contraindications").

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

Antagonists of vitamin K

As with other HMG-CoA reductase inhibitors, the initiation of Roxera treatment or a gradual increase in its dose in patients receiving concomitant vitamin K antagonists (eg warfarin or other indirect anticoagulants) may result in an increase in the international normalized ratio (MNF). After the cancellation of the Roxers or the reduction of the dose of the Emergency Ministry may decrease. In such cases, it is desirable to properly monitor the Ministry of Emergencies. In patients who use vitamin K antagonists, it is recommended to monitor the MES both at the start of treatment with Roxera, either after discontinuation or subsequent change in its dosage.

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 use of the Roxer drug and some combinations of protease inhibitors is possible after careful consideration of the dose adjustment of the Roxer preparation based on the expected growth of the exposure of rosuvastatin (see sections "Method of administration and dose", "Application features", "Interaction with other drugs and other mechanisms" , table 2).

Gemfibrozil and other hypolipidemic drugs

The simultaneous use of the drug Roxera and gemfibrosil resulted in a 2-fold increase in AUC and C max of rosuvastatin (see section "Special Features").

Based on these special studies of interaction, no significant pharmacokinetic interaction with fenofibrate is expected, however, a pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrate and niacin (nicotinic acid) in hypolipidemic doses (> 1 g / day) increase the risk of developing myopathy while co-administered with HMG-CoA reductase inhibitors, possibly because they are capable of leading to myopathy and when used separately. 40 mg Roxers dose is contraindicated when fibrates are co-administered.

Treatment with Roxera in such cases should also be started at a dose of 5 mg.

Ezetimib

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

Erythromycin

Concurrent use of Roxers and erythromycin reduced AUC (0-t) rosuvastatin by 20% and C max by 30%. Such an interaction may be due to increased intestinal motility 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. No clinically significant interactions were observed between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4) or ketoconazole (an inhibitor of CYP2A6 and CYP3A4).

Table 2
Effect of concomitant medications on exposure to rosuvastatin

(AUC, in decreasing order of 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 daily to 200 mg twice daily, 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
Symyprovir 150 mg once daily for 7 days 10 mg, once ↑ 2.8 times
Lopinavir 400 mg / ritonavir 100 mg twice daily for 17 days 20 mg once daily for 7 days ↑ 2.1 times
Gemfibrozil 600 mg twice daily, 7 days 80 mg, once ↑ 1.9 times
Eltromobopac 75 mg once daily for 5 days 10 mg, once ↑ 1.6 times
Darunavir 600 mg / ritonavir 100 mg twice a day, 7 days 10 mg once daily for 7 days ↑ 1.5 times
Tipranavir 500 mg / ritonavir 200 mg twice daily for 11 days 10 mg, once ↑ 1.4 times
Dronadarone 400 mg twice daily not known ↑ 1.4 times
Itraconazole 200 mg once daily, 5 days 10 mg, once ↑ 1.4 times **
Ezetimib 10 mg once daily for 14 days 10 mg once daily for 14 days ↑ 1.2 times **
Phasamprenavir 700 mg / ritonavir 100 mg twice daily for 8 days 10 mg, once
But glitazar 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 for 7 days 20 mg, once
Ketoconazole 200 mg twice daily, 7 days 80 mg, once
Fluconazole 200 mg once daily for 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%

* 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 interaction studies were conducted at various doses of rosuvastatin, and the most significant ratio is presented in the table.

Oral Contraceptives / Hormone Replacement Therapy (HRT)

Concurrent use of Roxers and oral contraceptives resulted in an increase in AUC of ethinyl estradiol and norgestrel by 26% and 34%, respectively. Increasing plasma levels should be considered when choosing a dose of oral contraceptives. Нет данных фармакокинетики препаратов у пациентов, которые одновременно принимают Роксеру и ГЗТ, поэтому возможность взаимодействия исключать нельзя. Однако такую комбинацию широко применяли женщинам в клинических исследованиях, и она переносилась хорошо.

Другие лекарственные средства

Исходя из данных специальных исследований, клинически существенного взаимодействия с дигоксином не ожидается.

В клинических исследованиях Роксеру сопутствующее применяли с антигипертензивными, противодиабетических средств и гормонозаместительной терапии. Эти исследования не показали никаких доказательств клинически значимых нежелательных взаимодействий.

Фузидова кислота

Риск миопатии, включая рабдомиолиз, может повышаться за счет сопутствующего системного применения фузидовои кислоты со статинами. Механизм этого взаимодействия (фармакодинамический или фармакокинетический), пока неизвестно. Были сообщения о рабдомиолиз (включая летальные исходы) у пациентов, которые получали эту комбинацию. Если системное лечение фузидовою кислотой необходимо, то применение розувастатина должно быть прекращено в течение всего периода лечения фузидовою кислотой.

Лопинавир / ритонавир

In pharmacological research and the simultaneous Application Rokserы kombynyrovannoho drugs, two inhibitors soderzhascheho proteazy (lopynavyr 400 mg / rytonavyr 100 mg) zdorovыh dobrovoltsev assotsyyrovalos with prymerno dvukratnыm and pyatykratnыm Increase indicators ravnovesnoho AUC (0-24) and smahu for rosuvastatin in accordance. Interaction Between Rokseroyu a second inhibitor proteazy not yzuchalys.

Where are you

Only interaction Study conducted in adults. Degree of interaction in children Unknown.

Application features

Influence on the kidneys

In patsyentov, poluchavshyh Rokseru in High doses, especially 40 mg, otmechalos cases of proteinuria (opredelennoj for "test stripes") preymuschestvenno tubular in origin and in Most cases vremennoy or neprodolzhytelnoy. Proteinuria not talk about Ostrom or progressive renal Disease. Nezhelatelnыe phenomenon in co storony kidney postmarketynhovыy period otmechaly chashche Application dozы at 40 mg. In patsyentov, prynymayuschyh in drug dose 30 or 40 mg kidney function sleduet Provera regularly.

Influence on skeletal muscle

Defeat muskulaturы bones, for example myalgia, myopathy, and rarely - rabdomyolyz nablyudalys in patsyentov at doses Rokserы Application vseh, especially at doses more than 20 mg. With Application эzetymyba in kombynatsyy with inhibitors of HMG-CoA reductase Very rarely cases was reported at rabdomyolyza development. Opportunity impossible ysklyuchat farmakodynamycheskoho interaction, and after such kombynatsyyu sleduet Apply with caution.

As a sluchae Application and second ynhybytorov HMG-CoA reductase, rabdomyolyza cases related primeneniem Rokserы in postmarketynhovыy sluchalys chashche period at dose of 40 mg. Ymeyutsya messages rarely cases of necrotizing myopathy ymmunooposredovannыh, Clinical proyavlyayutsya 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.

Definition urovnja CPK

It should not CPK level yzmeryat after znachytelnыh fyzycheskyh nahruzok or availability at vozmozhnыh alternatyvnыh reasons Increase creatine fosfokynazы, kotoryya mogut meshat interpretation of results. If creatine Initial Levels Significantly fosfokynazы povыshenы (> 5x upper boundaries norms) in 5-7 days techenye neobhodimo Set Additional podtverzhdayuschyy analyz.Esly result of re-analysis confirms the Initial Level> 5 x upper boundaries norms, the Start Treatment It should not.

Before Treatment

Rokseru, As a global Global ynhybytorov HMG-CoA reductase, sleduet with caution assign patsyentam with factors sposobstvuyuschymy development myopathy / rabdomyolyza. K such factors include:

  • violation kidney function
  • hypothyroidism
  • The presence of family or individually in anamneze nasledstvennыh muscle diseases;
  • The presence in anamneze myotoksychnosty, vыzvannoho second inhibitor of HMG-CoA reductase or fybratamy;
  • zloupotreblenye alcohol;
  • vozrast> 70 years;
  • situation, kotoryya mogut lead for drug urovnja Increase in plasma
  • Application simultaneous fibratov.

In such patsyentov Nuzhny Compare vozmozhnuyu risk and favor in the Application of the drug Is recommended also Clinical MONITORING. It should not sluchae in the Start Treatment Significantly povыshennыh nachalnыh CPK level (> 5 x VHN).

In the period of treatment

It should be at Patsyentov predupredyt Need nemedlenno Report neobъyasnymыy mыshechnaya pain, weakness or cramps mыshechnuyu, especially îíè If soprovozhdayutsya nedomohanyem Increase or temperature. In such patsyentov It should opredelyt CPK Levels. It should prekratyt Treatment, Level If CPK Significantly povыshenы (> 5hVMN) or mыshechnыe If symptoms Heavy vыzыvayut and discomfort in everyday life (Even If Level CPK ≤ 5 x ULN). If symptoms pass and Level CPK vozvraschaetsya for normal, or Rokseru Alternative inhibitor of HMG-CoA can be poprobovat Apply Dreams, but in doses mynymalnыh and control pod tschatelnыm nablyudenyem.Rehulyarnыy urovnja CPK in patsyentov without vыsheukazannыh symptomov nuzhen.

В клинических исследованиях у небольшого количества пациентов, которые применяли Роксеру и сопутствующие препараты, усиленного воздействия на скелетную мускулатуру не отмечали. Однако повышенная частота случаев миозита и миопатии наблюдалась у пациентов, применяющих другие ингибиторы ГМГ-КоА редуктазы с производными фиброевой кислоты, в том числе гемфиброзилом, циклоспорином, никотиновой кислотой, азольными противогрибковыми средствами, ингибиторами протеазы и макролидные антибиотики. Гемфиброзил повышает риск развития миопатии при одновременном применении с некоторыми ингибиторами ГМГ-КоА редуктазы, поэтому Роксеру не рекомендуется применять в комбинации с гемфиброзилом. Благотворное влияние дальнейших изменений уровня липидов при одновременном применении Роксеры с фибратами или ниацином нужно сравнить с потенциальными рисками при применении такой комбинации. Одновременное применение Роксеры в дозе 30 или 40 мг и фибратов противопоказано.

Роксеру не следует совмещать вместе с системным применения фузидовои кислоты или в течение 7 дней после прекращения лечения фузидовою кислотой. Для пациентов, для которых использование системной фузидовои кислоты считается необходимым, лечение статинами необходимо прекратить в течение всего периода лечения фузидовою кислотой. Были сообщения о случаях рабдомиолиза (включая летальные исходы) у пациентов, которые получали фузидову кислоту и статины в комбинации. Пациент должен немедленно обратиться к врачу, если он чувствует симптомы, такие как мышечная слабость, боль или вялость. Терапия статинами может быть повторно проведена через 7 дней после последней дозы фузидовои кислоты. В исключительных случаях, когда необходимо длительное системное применение фузидовои кислоты, например, для лечения тяжелых инфекций, необходимость одновременного назначения Роксеры и фузидовои кислоты следует рассматривать только в каждом конкретном случае и под тщательным медицинским наблюдением.

It should Rokseru with caution Apply patsyentam with factors sposobstvuyuschymy development myopathy, such As Renal failure, pozhyloy age, hypothyroidism, or in situations, when uvelychytsya Can Concentration in blood plasma.

It should not Rokseru Apply for patsyentov with ostrыmy, sereznыmy STATUS, myopathy sposobstvuyuschyh development or risk of development povыshayut renal insufficiency on the background rabdomyolyza (eg How sepsis, hypotension, obshyrnoe surgical intervention, trauma, metabolic Heavy, эndokrynnыe or electrolyte violations; nekontrolyruemыe spasms).

Influence on the liver

As others ynhybytorы and HMG-CoA reductase, Rokseru sleduet Apply caution with patients, zloupotreblyayuschym alcohol and / or with liver disease in history.

Liver function is recommended before the beginning the Review Application preparation and after 3 months of treatment. If Level transaminases in blood whey something more than tripled prevыshaet verhnyuyu border norms, Application Rokserы It should prekratyt. At sereznыh abuse liver function (preymuschestvenno urovnja pechenochnыh transaminases Increase) in postmarketynhovыy period was reported at chashche Application dozы 40 mg.

In patsyentov vtorychnoy with hypercholesterolemia, vыzvannoy hypothyroidism or nephrotic syndrome, snachala It should hold a primary disease Treatment and zatem the Start Application Rokserы.

In postrehystratsyonnыy yzredka period was reported at letalnыh or hepatic insufficiency neletalnыh cases in patsyentov, prynymavshyh statynы in volume including rosuvastatin. If the background of treatment for drug Roksera razvyvaetsya sereznoe defeat klynycheskoy symptomatykoy with liver and / or hyperbilirubinemia or zheltuhoy, nemedlenno It should prekratyt pryem drug. If others have been detected Causes, Treatment vozobnovlyat It should not Roksera drug.

Race

In research pharmacokinetics nablyudalsya GROWTH systemnoy Exposition in patsyentov monholoydnoy rasы compared to Europeans.

For such patsyentov neobhodyma correction dozы drug Roksera (cm. Sections "Method and Application dozы" and "Pharmacokinetics"). For patsyentov monholoydnoy rasы nachalnaya Rokserы dolzhna bыt dose of 5 mg. Concentration at peak times rosuvastatin plasma bыla zamechena in azyatskyh patsyentov (see. Section "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 drug Roksera in patsyentov with HIV, kotoryya poluchayut ynhybytorы proteazy well and Increase Ability rosuvastatin concentrations in plasma in early therapy and at Increase dozы Rokserы for patsyentov, poluchayuschyh ynhybytorы proteazy. Application with simultaneous drug proteazy inhibitors is not recommended, If not skorrektyrovannыe Rokserы dose (see. Section "Method and Application dozы" and "Interaction with the second lekarstvennыmy funds and others types vzaymodeystvyy").

lactose intolerance

Patsyentam redkoy with hereditary galactose neperenosymostyu, laktazы Lappa deficit or glucose-galactose malabsorption It should not Apply this product.

Interstitial pulmonary Disease

Edynychnыe cases of interstitial lung disease bыly zarehystryrovanы Application nekotorыh with statins, especially in sluchae dlytelnoy therapy. K otnosjatsja odыshka violations symptoms, cough and neproduktyvnыy uhudshenye STATUS, general (fatigue, pulmonary embolism Fire-proof compounds and rubbed fever). If podozrevaetsya, something in patsyenta razvylos interstitial lung Disease, Application statins sleduet prekratyt.

Saharnыy diabetes

Некоторые факты свидетельствуют, что статины повышают уровень глюкозы в крови и в некоторых пациентов, которым грозит высокий риск развития диабета в будущем, могут вызывать гипергликемию такого уровня, при котором необходимо надлежащее лечение диабета. Эту угрозу, однако, превышает снижение риска сосудистых нарушений при применении статинов, и поэтому она не должна быть основанием для прекращения терапии статинами. Пациенты группы риска (уровень глюкозы натощак 5,6-6,0 ммоль / л, ИМТ> 30 кг / м 2 , повышенный уровень триглицеридов, артериальная гипертензия) следует установить как клинический, так и биохимический контроль в соответствии с национальными установками.

В исследованиях зарегистрировано общая частота сахарного диабета составила 2,8% в группе приема розувастатина и 2,3% - в группе плацебо, преимущественно у пациентов с уровнем глюкозы натощак от 5,6 до 6,9 ммоль / л.

Как и в других ингибиторов ГМГ-КоА-редуктазы, при применении розувастатина наблюдался рост HbA1c и уровня глюкозы в сыворотке крови. В некоторых случаях эти показатели могут превышать предельное значение для диагностики сахарного диабета, прежде всего у пациентов с высоким риском развития диабета.

In Clinical Studies It would show something Roksera monotherapy in kachestve not vыzыvaet Reduction bazovoy plasma concentrations of cortisol and blood not vlyyaet allowance nadpochechnykov.Neobhodyma ostorozhnost while simultaneously Application drug Roksera and second lekarstvennыh funds, sposobnыh snyzhat Level эndohennыh activity or steroid hormones, for example ketoconazole, spironolactone and cimetidine.

Dety and podrostky in age from 10 to 17 years

The influence of rosuvastatin on linear growth (body height), body weight, BMI (body mass index), and the development of secondary Tanner markers at the age of 10-17 years was evaluated for only one year. After 52 weeks of treatment, no effect on growth, body weight, BMI, or puberty was found (see Section "Pharmacological"). The experience of clinical trials in children and adolescents is limited, and the long-term effects of rosuvastatin (> 1 year) on puberty are unknown.

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 safety of the use of Roxers during pregnancy and breast-feeding has not been studied.

A roxera is contraindicated during pregnancy and breastfeeding.

Women of childbearing age should receive appropriate contraceptive measures when taking Roxers.

As cholesterol and other cholesterol biosynthesis products are essential for fetal development, the potential risk of inhibition of HMG-CoA reductase exceeds the potential benefits of using the drug during pregnancy. If the patient becomes pregnant during the period of application, the 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 with Roxer 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.

No studies were conducted to determine the effect of rosuvastatin on the ability to drive a car and other mechanisms.Based on the pharmacodynamic properties of rosuvastatin, the probability of such an effect is negligible. However, when driving a car and other mechanical means, it should be taken into account that dizziness may occur during treatment.

Method of administration and dose.

Before starting treatment, a standard hypocholesterolemic diet should be prescribed to the patient, which should be followed during treatment. The dose should be selected individually, depending on the purpose of the therapy and the effectiveness of the treatment, applying the current agreed recommendations.

A boxer can be taken at any time of the day, regardless of meals.

The tablet should not be chewed or crushed. Swallow the tablet whole with water.

Treatment of hypercholesterolemia

The recommended starting dose is 5 or 10 mg orally once daily for both patients who have not previously taken statins and for patients who have previously been prescribed other HMG-CoA reductase inhibitors. Choosing the starting dose should take into account the individual cholesterol level in patients and the future cardiovascular risk, as well as the potential risk of side effects (see below). If necessary, after 4 weeks, the dose can be increased to the next. Since in the case of a dose of 40 mg, adverse reactions occur more often than at lower doses, titration of the dose up to 30 mg to 40 mg should only be performed in patients with severe hypercholesterolemia and high cardiovascular risk (in particular, in persons with familial hypercholesterolaemia), in whom failed to achieve the desired result for a dose of 20 mg and should be under regular observation. At the start of the dose of 30 mg or 40 mg, specialist supervision is recommended.

Prevention of cardiovascular disorders

In the study, the reduction in the risk of complications from the cardiovascular system, the daily dose was 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

The recommended starting dose for patients over the age of 70 years is 5 mg. No other dose adjustments are required depending on age.

application for children

The usual dose for children and adolescents 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.

Dosage for patients with impaired kidney function

For patients with mild to moderate renal impairment, no dosage adjustment is required. The recommended initial dose for patients with moderate renal impairment (creatinine clearance <60 ml / min) is 5 mg. The dose of 30 mg and 40 mg is contraindicated in patients with moderate renal impairment. For patients with severe renal impairment, the use of Roxers is contraindicated in any dose.

Dosage for patients with impaired liver function

There was no increase in systemic exposures of rosuvastatin in patients with a score of 7 on the Child-Pugh scale.However, the increase in systemic exposure was noted in patients whose status was estimated at 8 and 9 points on the Child-Pugh scale. Such patients should be evaluated for renal function. Experience in using the drug in patients with a score of 9 points on the Child-Pugh scale is absent. A rokker is contraindicated in patients with active liver disease.Patients with severe liver function impairment showed an increase in exposure to rosuvastatin, and therefore they should be administered with a dose of above 10 mg to Precaution.

Race

Patients in the Mongoloid race have an increased systemic exposure to the drug. The recommended initial dose for Asian patients is 5 mg. The dose of 40 mg for these patients is contraindicated. 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 the genotype c.521CC or c.421AA, the maximum recommended daily dose of Roxers is 20 mg.

Rosevastatin is a substrate for various transport proteins (e.g., OATP1B1 and BCRP). Myopathy (including rhabdomyolysis) increases with concomitant administration of Roxers with certain drugs that can increase the plasma concentrations of roseuvastatin through interaction with these transport proteins (eg, cyclosporin and some protease inhibitors, including combinations of ritonavir with atnazavir, lopinavir and / or tipranavir). If possible, alternative treatment should be considered and, if necessary, temporarily stop treatment with Roxera. In situations where the simultaneous administration of these drugs with Roxera can not be avoided, we must weigh all the benefits and risks of concomitant treatment and carefully select the dose of Roxers.

Where are you.

Do not use Roxers for children under 10 years of age.

The influence of rosuvastatin on linear growth (body height), body weight, BMI (body mass index), and the development of secondary Tanner markers at the age of 10-17 years was 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

No specific treatment in case of overdose. Symptomatic treatment. If necessary, take supportive measures. You should check the level of KFK and conduct a liver function test. The unlikely benefits of carrying out hemodialysis.

Adverse reactions

Side effects observed with the application of Roxers are usually mild and transient.

From the side of the immune system
Hypersensitivity reactions, including angioneurotic edema.

From the endocrine system
Diabetes mellitus 1,2 .

From the nervous system
Headache, dizziness.

From the digestive system
Constipation, nausea, abdominal pain, pancreatitis.

From the skin and subcutaneous tissue
Itching, rash and urticaria.

On the part of the musculoskeletal system of the connective tissue and bones
Myalgia, myopathy (including myositis) and rhabdomyolysis.

General condition
Asthenia

As with other HMG-CoA reductase inhibitors, the incidence of adverse reactions is dose-dependent.

1 Frequency is dependent on the presence of risk factors (fasting blood glucose ≥ 5.6 mmol / l, body mass index> 30 kg / m 2 , triglyceride increased, history of hypertension).
2 According to the results of the JUPITER study (the overall frequency of reports with rosuvastatin - 2.8%, placebo - 2.3%) is primarily in patients already at high risk of developing diabetes mellitus.

Influence on the kidneys

Patients who received Roxer had cases of proteinuria, primarily tubular origin (defined as "strip test"). Changes in the urine protein content from absence or trace amounts to ++ or greater are reported after a short time in <1% of patients taking the drug at a dose of 10 mg and 20 mg and in about 3% of patients at a dose of 40 mg. A slight increase in the incidence of cases an increase in urine protein from absence or traces to + was observed at a dose of 20 mg. In most cases, the severity of proteinuria decreased or disappeared spontaneously with continued use of the drug. A review of data from clinical studies and postmarketing observations has currently found no causal link between proteinuria and acute or progressive kidney disease.

Hematuria was observed in patients who received Roxer and clinical data suggest a low incidence of hematuria.

Influence on skeletal muscle

On the part of the skeletal muscles, such as myalgia, myopathy (including myositis), and rarely, rhabdomyolysis with or without acute renal failure has been observed with the use of any dose of Roxers, especially when dosages of> 20 mg are used. Of rare cases of rhabdomyolysis, sometimes associated with renal failure, has been reported with the use of rosuvastatin, as well as other statins.

In patients taking rosuvastatin, there was a dose-dependent increase in the levels of KFK (CPK), in most cases the event was mild, asymptomatic and temporary. If the levels of KFK are elevated (> 5 x upper limit of the norm (VMN)), treatment should be discontinued.

Influence on the liver

As with other HMG-CoA reductase inhibitors, a small proportion of patients taking rosuvastatin experienced dose-dependent elevation of transaminases; in most cases the phenomenon was weak, asymptomatic and temporary.

Effect on laboratory parameters

As with other HMG-CoA reductase inhibitors, a small proportion of patients taking rosuvastatin had a dose-proportional increase in hepatic transaminases and CPC. The use of rosuvastatin also indicated an increase in HbA1c levels. In a small number of patients who used Roxeter and other HMG-CoA reductase inhibitors, pathological changes were observed in urine analysis (the test strip was evidence of proteinuria). The revealed protein was, as a rule, tubular reconciliation. In most cases, proteinuria becomes less pronounced or disappears spontaneously with continued therapy and does not indicate an acute or progressive kidney disease.

Other effects

In prolonged controlled clinical trials, Roxer did not show any adverse effects on the eye lens.

In patients who were treated with Roxera, there were no violations of the functions of the adrenal cortex.

Post-marketing experience

In addition to the aforementioned, in the postmarketing period of the application of the Roxers, the following phenomena were recorded:

  • from the nervous system: polyneuropathy, memory loss, peripheral neuropathy;
  • from the respiratory system , thoracic and mediastinal organs: cough, shortness of breath;
  • from the digestive system: diarrhea
  • from the digestive system: jaundice, hepatitis, increased activity of hepatic transaminases;
  • from the side of the skin and subcutaneous tissue : Stevens-Johnson syndrome
  • from the bone-muscle system: immuno-mediated necrotizing myopathy, arthralgia. from the side of the tendons, sometimes complicated by ruptures, immuno-mediated necrotizing myopathy;
  • from the side of the kidneys: hematuria
  • general condition and disorders related to the method of application of the drug: edema
  • on the part of the reproductive system and mammary glands: gynecomastia
  • from the side of the blood: thrombocytopenia.

When using some statins, the following side effects were reported:

  • depression
  • sleep disorders, including insomnia and nightmares;
  • sexual dysfunction;
  • isolated cases of interstitial lung disease, especially in the case of long-term therapy;
  • diseases of the tendons, sometimes complicated by their rupture.

The frequency of cases of rhabdomyolysis, severe renal and hepatic impairment (predominantly elevated transaminase levels) was higher with a dose of 40 mg.

In the process of post-surgical use of rosuvastatin, such an undesirable reaction 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).

Children and teens from 10 to 17 years old

The safety profile of Roxers in children, adolescents and adults is similar, although in clinical trials in children and adolescents after exercise or significant physical activity, increased CPK> 10μM and muscle symptoms were more often observed, and subsequently passed without interruption of treatment. However, for both children and adult precautions, the use of Roxers is the same.

Shelf life

3 years.

Storage conditions

Store in original packaging to protect against light exposure. The preparation does not require special temperature storage conditions.

Keep out of the reach of children.

Packaging

For tablets of 5 mg or 10 mg, or 15 mg or 20 mg
10 tablets in a blister, 1 or 2, or 3, or 6, or 9 blister cards in a cardboard box
14 tablets in a blister, 1 or 2, or 4 blister in a cardboard box.

For tablets of 30 mg or 40 mg
10 tablets in a blister, 1 or 2, or 3, or 6, or 9 blister cards in a cardboard box
7 tablets in a blister, 2 or 4, or 8 blister cards in a cardboard box.

Vacation category

By recipe


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