Rosulip® (Rosuvastatin) 20 mg, 28 coated tablets
- $44.20
РОЗУЛИП®
the Trade name
of Rozulip®
the International unlicensed
name Rosuvastatin Dosage Form
of the Tablet, coated 10 mg, 20 mg, 40 mg
Structure
One tablet contains
active agent - rosuvastatin of 10 mg, 20 mg and 40 mg (10.68 mg, 21.36 mg and 42.72 mg of rosuvastatin of zinc, respectively are equivalent),
excipients: ludipress (lactoses monohydrate, povidone, krospovidon), krospovidon (XL10), magnesium stearate, Opadry II white 85F 18422 (polyvinyl alcohol, titan E 171 dioxide, macrogoal 3350, talc.
The description
White or almost white, round slightly biconvex tablets, coated, without or almost flavourless, with an engraving of the stylized letter E on one party and number 592 – on other party of a tablet (for a dosage of 10 mg).
White or almost white, round slightly biconvex tablets, coated, without or almost flavourless, with an engraving of the stylized letter E and number 593 on one party of a tablet (for a dosage of 20 mg).
White or almost white, oval slightly biconvex tablets, coated, without or almost flavourless, with an engraving of the stylized letter E and number 594 on one party of a tablet (for a dosage of 40 mg).
Pharmacotherapeutic group
Hypolipidemic drugs. Reductase HMG-CoA inhibitors.
The ATX C10A A07 code
the Pharmacological
Pharmacokinetics Maximum Concentration properties of rosuvastatin in blood plasma is reached approximately in 5 hours after oral administration. The absolute bioavailability is about 20%. Rosuvastatin is absorbed, mainly, by a liver where there is the main synthesis of cholesterol and removal of Hs-LPNP. The volume of distribution of rosuvastatin is about 134 l. About 90% of rosuvastatin contact proteins of plasma, mainly albumine. Rosuvastatin in insignificant degree is exposed to metabolism (about 10%). Rosuvastatin is non-core substrate for isoenzymes of a system of P450 cytochrome. The main enzyme participating in rosuvastatin metabolism is CYP2C9. CYP2C19, CYP3A4 and CYP2D6 enzymes are involved in metabolism to a lesser extent. The main derivatives of rosuvastatin are N-desmetil and lactonic metabolites. N-desmetil for about 50% is less active, than rosuvastatin, lactonic derivatives are pharmacological not active. Rosuvastatin provides suppression of activity of more than 90% of the circulating HMG-CoA-reductase. About 90% of a dose of rosuvastatin are removed in not changed view with excrements (including the absorbed and not absorbed rosuvastatin). The rest of a dose is removed with urine. About 5% of a dose of drug are excreted with urine in not changed state. Elimination half-life of drug makes about 19 hours of blood plasma. Elimination half-life does not change at increase in a dose of drug. The average geometrical plasma clearance is about 50 liters/hour (coefficient of variation of 21.7%). Similar to other HMG-CoA-reductases inhibitors, in the course of hepatic capture of rosuvastatin the membrane protein carrier of organic anions like C (OATP-C) which is carrying out an important role in hepatic elimination of Rozulip participates. The system bioavailability of rosuvastatin increases in proportion to a dose. When using drug several times in day the pharmacokinetic parameters do not change.
As well as in case of other HMG-CoA-reductases inhibitors, the membrane carrier of cholesterol who is carrying out an important role in hepatic elimination of Rozulip is involved in process of hepatic capture of rosuvastatin.
System exposure of rosuvastatin increases in proportion to a dose.
Special groups of patients
Age and sex: Clinically significant influence of age and sex on pharmacokinetic properties of rosuvastatin was not noted. The rosuvastatin pharmacokinetics at use for children and teenagers with a family heterozygous hypercholesterolemia was similar to pharmacokinetics of adult patients.
Race: Results of pharmacokinetic researches demonstrate that in comparison with persons of white Caucasian race, at persons of Asian race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) average area under a curve concentration time (area under the curve, AUC) and the maximum concentration of drug in blood plasma (Cmax) is approximately twice higher. At Hindus these indicators are approximately 1.3 times higher, than at persons of white race. The analysis of population pharmacokinetics did not reveal clinically significant differences in pharmacokinetic parameters of rosuvastatin between persons of white and negroid race.
Patients with a renal failure. The slight or moderate renal failure did not influence concentration of rosuvastatin or a N-desmetil-metabolite in blood plasma. At patients with a heavy renal failure (clearance of creatinine
the Pharmacodynamics
Rozulip – a selection, competitive inhibitor of HMG-CoA-reductase – the enzyme catalyzing transformation of 3-hydroxy-3-methylglutaryl-coenzyme A in mevalonat, the predecessor of cholesterol. The main target of effect of rosuvastatin is the liver where synthesis of cholesterol (XC) and catabolism of lipoproteins of the low density (LDL) is carried out.
Rosuvastatin increases the number of hepatic receptors of LDL by surfaces of cells at the expense of what capture and catabolism of LDL amplifies and synthesis of lipoproteids of very low density (LPONP) in a liver is suppressed. As a result the total number of LPONP and LDL decreases.
Rozulip reduces the increased content of LDL cholesterol (Hs-LPNP), the general cholesterol and triglycerides (TG), increases the level of cholesterol of lipoproteids of the high density (Hs-LPVP) and also reduces apolipoprotein B content (ApoV), cholesterol NELPVP (Hs-neLPVP), LPONP cholesterol (Hs-LPONP), LPONP (TG-LPONP) triglycerides and increases the content of A-I apolipoprotein (ApoA-I), reduces a ratio of Hs-LPNP/Hs-LPVP, the general cholesterol / Hs-LPVP, Hs-neLPVP/Hs-LPVP and ApoV/ApoA-I. (see Table 1).
Table 1. Effects of various doses of drug at treatment of patients with primary hypercholesterolemia (IIa and IIb type) (the corrected average percentage changes in comparison with initial level)
the Dose
of N Hs-LPNP Obshchy
ApoAI ApoV Hs-LPVP Triglitseridy Hs-neLPVP cholesterol
of Placebo
of 13 - 7 - 5 3 - 3 - 7 - 3 0 5
mg 17 - 45 - 33 13 - 35 - 44 - 38 4 10 mg 17 - 52 - 36 14 - 10 - 48 - 42 4 20 mg 17 - 55 - 40 8 - 23 - 51 - 46 5 40 mg
18
-
63 - 46 10 - 28 - 60 - 54 0
The therapeutic effect is shown within one week after the beginning of therapy by drug, in 2 weeks of treatment reaches 90% of the greatest possible effect. The maximum therapeutic effect is usually reached by 4th week and maintained at regular reception.
Rozulip is effective at treatment of most of patients with a hypercholesterolemia of IIa and IIb of type (average Hs-LPNP initial level is about 4.8 mmol/l) and corresponds to the target indicators provided in the recommendations of the European society of studying atherosclerosis (European Atherosclerosis Society, EAS, 1998). About 80% of the patients taking the drug in a dose of 10 mg reached the target Hs-LPNP level (
Indications
- primary hypercholesterolemia (type II and: hereditary defect ApoV, an autosomal and recessive hypercholesterolemia, an autosomal and prepotent hypercholesterolemia, a sitosterolemiya, a polygenic hypercholesterolemia) or the mixed dislipidemiya (IIb type) as addition to a diet, in cases when correction of food and other non-drug methods of treatment (for example, physical exercises, decrease in body weight) are insufficiently effective
- treatment of a homozygous hereditary hypercholesterolemia as addition to a diet and other methods of treatment directed to decrease in level of lipids in blood (for example, LPNP-aferez) and also in cases when these methods are insufficiently effective
- prevention of the undesirable cardiovascular phenomena at patients, with a high probability of predisposition to the first cardiovascular phenomenon as addition to correction of other risk factors
- treatment of atherosclerosis at the patients needing lipidosnizhayushchy treatment for delay of progressing of a disease.
The route of administration and doses
use Drug strictly on doctor's orders!
Rozulip it is possible to accept at any time, irrespective of meal. Prior to the beginning of and during all course of therapy by Rozulip the patient has to keep to a standard diet with the low content of cholesterol. The dose of drug should be selected individually, depending on the purposes of therapy and the response to treatment.
The recommended initial dose of drug for the patients receiving therapy by other HMG-CoA-reductases inhibitor and also for persons who did not accept before statines makes 5 or 10 mg once a day. When choosing an initial dose it is necessary to be guided by the level of content of cholesterol and to take possible risk of cardiovascular complications into account and also it is necessary to estimate potential risk of development of side effects. In case of need, the dose can be increased after 4 weeks of administration of drug.
Due to the possible development of side effects at reception of a dose of 40 mg, increase in a dose to the maximum 40 mg can be considered only at patients with a heavy hypercholesterolemia and with high risk of cardiovascular complications (especially at a hereditary hypercholesterolemia) at which the desirable result of therapy at reception of a dose of 20 mg was not achieved. Observation of the patients receiving drug in a dose of 40 mg is recommended. And also, it is recommended to begin therapy with the drug Rozulip in a dose of 40 mg under control of the doctor.
Use for children and teenagers
Use for children and teenagers has to be carried out only under control of the expert.
Children and teenagers from 10 to 17 years (boys at Tanner II'S stage above, girls at least in a year after the beginning of a menstrual cycle):
For children and teenagers with a heterozygous family hypercholesterolemia the usual initial dose makes 5 mg a day. Usual range of doses – 5-20mg in day orally. According to the recommendations of use in pediatrics, increase in a dose has to be carried out depending on the individual answer and shipping of patients. Prior to treatment by rosuvastatin children and teenagers should appoint a standard holestirinoponizhayushchy diet which should be observed also during treatment. Safety and efficiency of the doses exceeding 20 mg for this group of patients it was not studied.
Tablets of 40 mg should not be applied to treatment of the patients who did not reach 17 years.
Experience of use of drug for children aged up to 10 years (aged from 8 up to 10 years) suffering from a homozygous hereditary hypercholesterolemia is limited. Therefore treatment by rosuvastatin of children aged up to 10 years is not recommended.
Elderly patients
dose adjustment is not required. The recommended initial dose of drug for patients is more senior than 70 years makes 5 mg.
Patients with a renal failure
with a renal failure easy or moderate severity dose adjustment is not required From patients. At patients with moderate renal failures (the clearance of creatinine
Patients with a liver failure
Is absent experience of use of drug for patients with assessment higher than 9 points on Child-Pugh scale. Nevertheless, at patients with assessment of 8 and 9 balls on a scale of Child-Pugh the increase in system bioavailability was observed. The drug Rozulip is contraindicated to patients with liver diseases in an active phase.
The race
the Increased system bioavailability of drug was registered at patients of Asian race. For persons of Asian origin the recommended initial dose of drug makes 5 mg. Therapy by Rozulip in a dose of 40 mg is contraindicated to patients of this group.
The patients predisposed to a myopathy
prescribing of drug in a dose of 40 mg is contraindicated to patients with the factors predisposed to development of a myopathy the Recommended initial dose for this group of patients makes 5 mg.
Side effects
Often (from> 1/100 to
- a headache, dizziness
- a constipation, nausea, an abdominal pain
- myalgia
- an asthenia
- sugar diabet1
Infrequently (from> 1/1000 to
- an itching, rash, urticaria
Seldom (from> 1/10000 to
- reactions of hypersensitivity, including a Quincke's disease
- a myopathy (including a miositis) and a rhabdomyolysis
- increase in level of hepatic transaminases in blood serum, pancreatitis
Very seldom (
-polyneuropathy
- memory loss
- jaundice, hepatitis
- an arthralgia
- a hamaturia
- a gynecomastia
Frequency is unknown (it is impossible to define proceeding from available data)
- cough, short wind
- diarrhea
- Stephens-Johnson's syndrome
- hypostasis
- interstitial diseases of lungs
As well as at use of other HMG-CoA-reductases inhibitors, the frequency of emergence of side effects has dose-dependent character.
At some patients taking the drug the dose-dependent increase in concentration of a creatine kinase was revealed. In most cases, this phenomenon had easy, asymptomatic and passing temper. At the increased concentration of a creatine kinase in blood serum (more than by 5 times in comparison with VGN) therapy by Rozulip should be stopped.
As well as in case of intake of other HMG-CoA-reductases inhibitors, at a small amount of the patients accepting Rozulip the dose-dependent increase in content of transaminases in blood serum which in most cases, had easy, asymptomatic and passing temper was observed.
Against the background of therapy some statines registered the following by-effects: sleep disorders, including insomnia and dreadful dreams, disturbances of sexual function, the depression, very exceptional cases of an interstitial disease of lungs registered generally at long-term therapy by statines.
Frequency of development of a rhabdomyolysis, the profound renal failures and serious violations from a liver (which are generally given by increase in concentration of transaminases) above when using drug in a dose of 40 mg.
1 Frequency of cases of diabetes will depend on existence or lack of risk factors (a glucose indicator on an empty stomach ≥ 5.6 mmol/l, body mass index> 30kg/sq.m, increase in level of triglycerides, the increased arterial blood pressure).
At the patients accepting rosuvastatin the proteinuria, in most cases canalicular on a proiskhozhdeniiya, determined by the test by means of an indicator strip was observed. Changes in protein of urine from its total absence or a small amount to ++ or it was more observed at 1% of patients during treatment by a dosage of 10 mg or 20 mg and approximately at 3% of the patients accepting a dose of 40 mg. Small increase from total absence or a small amount to + was observed at reception of a dose of 20 mg. In most cases at continuous treatment the proteinuria decreased or disappeared. On the basis of information obtained during clinical trials, and post-registration experience the lack of interrelation between a proteinuria and the acute or progressing renal failure is till today established.
Increase in level of a creatine kinase in 10 times more of the upper bound of norm and also the muscular symptoms following exercises or the increased physical activity were observed more often during 52-hnedelny clinical trial of children and teenagers, in comparison with adults. On other indicators the results of a research of safety of rosuvastatin at children, teenagers and adults match.
Contraindications
- hypersensitivity to rosuvastatin or any of drug components
- liver diseases in an active phase, including permanent increase
in concentration of transaminases in blood serum and any increase in activity of transaminases in blood serum (more than by 3 times in comparison with the upper bound of norm)
- the profound renal failures (clearance of creatinine
- a myopathy, predisposition to development of miotoksichesky complications
- a concomitant use of cyclosporine
- pregnancy and the period of a lactation
-use for women of reproductive age who do not use
effective methods of contraception
- children's age up to 10 years
the Therapy by the drug Rozulip in a dose of 40 mg is contraindicated:
To patients with the factors contributing to development of a myopathy (rhabdomyolysis):
- a renal failure of moderate severity (clearance of creatinine
- a hypothyroidism
- muscular diseases in the anamnesis
- the myopathy connected with intake of other HMG-CoA inhibitors - reductase or fibrat in the anamnesis
- an alcohol abuse
- states which can lead to increase in plasma
concentration of rosuvastatin
- patients of Asian race
- a concomitant use of fibrat
- children and teenagers up to 17 years
Medicinal interactions
Cyclosporine. At simultaneous use with Rozulip, indicators of AUC rosuvastatin were about 7 times higher, than at monotherapy by drug at healthy faces. Simultaneous use of rosuvastatin and cyclosporine does not affect plasma concentration of cyclosporine.
Antagonists of vitamin K. As well as in case of therapy by other HMG-CoA-reductases inhibitors, the beginning of therapy or increase in a dose of Rozulip at the patients receiving at the same time antagonists of vitamin K (for example, warfarin or other anticoagulants derivative coumarin), can be followed by increase in the international normalized relation (INR). After the termination of reception of Rozulip or decrease in its dose, MNO can decrease. In such cases the monitoring of MNO is recommended.
Gemfibrozil and other drugs reducing the maintenance of lipids in blood. Gemfibrozit simultaneous use and Rozulipa was followed by double increase in Cmax and AUC rosuvastatin. Based on data on specific interaction, significant interaction with fenofibraty, perhaps pharmakodinamichesky interaction is not expected pharmacokinetically. Gemfibrozil, fenofibrat, other fibrata and also Niacinum (niacin) in the doses reducing the maintenance of lipids in blood (1 g/day or more), increase risk of development of a myopathy at simultaneous use with HMG-CoA-reductases inhibitors, it is possible because they can cause a myopathy and when using as monotherapy. Therapy by Rozulip in a dose of 40 mg is contraindicated at the accompanying use of fibrat. At the accompanying therapy from fibrata the recommended initial dose of rosuvastatin has to make 5 mg.
Ezetimib. At simultaneous use with Rozulip the changes of AUC or Cmax of these drugs did not note. Nevertheless, between Rozulip and ezetimiby it is impossible to exclude pharmakodinamichesky interaction with development of side effects.
Inhibitors of proteases. In spite of the fact that the exact mechanism of interaction is unknown, simultaneous use of inhibitors of proteolytic enzymes can lead to significant increase in bioavailability of rosuvastatin. According to results of a pharmacokinetic research at simultaneous use of Rozulip in a dose of 20 mg and the combined drug of inhibitors of proteases (400 mg lopinavira/100 the mg of a ritonavir) at healthy volunteers noted increase in AUC0-24 and Cmax of rosuvastatin in an equilibrium state, respectively, in 2 and 5 times. Therefore the concomitant use of rosuvastatin and inhibitors of proteases at treatment of patients with HIV is not recommended.
Antacids. Simultaneous use of Rozulip and the suspension of an antacid containing aluminum and magnesium hydroxide was followed by decrease in concentration of rosuvastatin in blood plasma approximately for 50%. This effect decreased if patients accepted an antacid in 2 hours after Rozulip. The clinical importance of this interaction is not established.
Erythromycin. Simultaneous use of Rozulip and erythromycin was characterized by reduction of AUC0-t and Cmax of rosuvastatin, respectively, for 20 and 30%.
Oral contraceptives / gormonozamestitelny therapy (ZGT). Simultaneous use of Rozulip and oral contraceptives was followed by increase in AUC ethinylestradiol and Norgestrelum by 26 and 34%, respectively Increase in concentration of these hormones in blood plasma needs to be considered at selection of doses of oral contraceptives. The pharmacokinetic data characterizing Rozulip's use against the background of ZGT are absent therefore it is impossible to exclude development of the effects similar to above. However, such therapy was widely performed within clinical trials and differed in good tolerance in patients.
Digoxin. Clinically significant interaction of Rozulip and digoxin is improbable.
P450 cytochrome enzymes. Rosuvastatin is not inhibitor or the inductor of isoenzymes of a system of P450 cytochrome. Besides, rosuvastatin – non-core substrate for these isoenzymes. Between rosuvastatin and flukonazoly (CYP2C9 and CYP3A4 inhibitor) or ketokonazoly (CYP2A6 and CYP3A4 inhibitor) clinically significant interaction was not observed. The accompanying Rozulip's use and an itrakonazola (CYP3A4 inhibitor) was followed by increase in AUC rosuvastatin by 28%. Such changes are not considered as clinically significant. Thus, the medicinal interaction connected with the drug metabolism mediated by isoenzymes of a system of P450 cytochrome is improbable.
Special instructions
Influence on function of kidneys
At some patients accepting Rozulip (especially in a dose of 40 mg), the proteinuria was observed. The proteinuria was diagnosed in the analysis of urine by means of indicator strips. In most cases, it had canalicular origin, had passing or intermittent character. Changes of protein content from total absence and traces to ++ or were more observed less than at 1% of the patients receiving drug in a dose of 10 or 20 mg and also approximately at 3% of the patients taking the drug in a dose of 40 mg. The minimum changes of protein content in urine from total absence and traces to + were found in the patients taking the drug in a dose of 20 mg. In most cases the proteinuria decreases or disappears in the course of therapy and does not mean emergence sharp or progressing of the existing disease of kidneys. Within standard inspection of the patients receiving drug in this dose it is necessary to carry out assessment of function of kidneys.
Influence on skeletal muscles
By-effects from skeletal muscles (for example, myalgia, a myopathy (including mozit), and, in rare instances, a rhabdomyolysis with an acute renal failure or without it) were observed at the patients taking the drug in any doses, especially often in the doses exceeding 20 mg. Very seldom the rhabdomyolysis developed at the accompanying therapy ezetimiby and HMG-CoA-reductases inhibitors. At simultaneous use of these drugs it is impossible to exclude pharmakodinamichesky interaction and it is necessary to be careful.
As well as in case of therapy by other HMG-CoA inhibitors - reductases, the frequency of development of a rhabdomyolysis, the profound renal failures and serious violations from a liver (which are generally given by increase in concentration of transaminases) above when using drug in a dose of 40 mg.
Definition of concentration of a creatine kinase
Determination of level of a creatine kinase in blood serum should not be carried out after intensive physical activity or in the presence of other possible reasons of increase in concentration of a creatine kinase as it can complicate interpretation of results. If the initial level of a creatine kinase is considerably increased (5 times higher, than the upper bound of norm), in 5 - 7 days it is necessary to take repeated measurement. It is not necessary to begin therapy if the repeated test confirms the initial level of a creatine kinase (more than 5 times higher in comparison with the upper bound of norm).
Prior to therapy
As well as other inhibitors of HMG-CoA-reductase, Rozulip patients need to appoint with care with the factors contributing to development of a myopathy (rhabdomyolysis): the renal failure, a hypothyroidism, hereditary pathology of a muscular system at the patient or his immediate family, the myopathy connected with intake of other HMG-CoA inhibitor - reductase or the fibrat in the anamnesis, an alcohol abuse, age is more senior than 70 years, situations at which increase in concentration of rosuvastatin in blood plasma, the accompanying use of fibrat can be observed.
When prescribing drug such patients need to weigh carefully potential risk of therapy and possible advantage. Besides, it is recommended to carry out clinical monitoring.
During therapy
the doctor Should inform the patient on need of the immediate message about cases of unexpected appearance of muscular pains, muscle weakness or spasms, especially if they are followed by an indisposition and fever. At such patients it is necessary to determine creatine kinase level in blood serum. Therapy has to be stopped if the level of a creatine kinase is considerably increased (more than by 5 times in comparison with the upper bound of norm) or if symptoms from muscles are pronounced and cause daily discomfort (even if the level of a creatine kinase is 5 times less in comparison with the upper bound of norm). If symptoms disappear and the level of a creatine kinase returns to norm, it is necessary to consider a question of repeated appointment of Rozulip or other HMG-CoA-reductases inhibitors in smaller doses at careful observation of the patient. Routine control of a creatine kinase in the absence of symptoms is not reasonable.
Signs of increase in impact on skeletal muscles at Rozulip's reception and the accompanying therapy are noted. It was reported about increase in cases of a miositis and a myopathy at the patients accepting other inhibitors of HMG-CoA-reductase in combination with derivatives of fibrinous acid, including gemfibrozit, cyclosporine, niacin, azolny antifungal means, inhibitors of proteases and makrolidny antibiotics. Gemfibrozil increases risk of emergence of a myopathy at the combined appointment with some HMG-CoA inhibitors - reductases. Thus, co-administration of Rozulip and a gemfibrozil is not recommended. The ratio of risk and possible advantage at combined use of Rozulip and fibrat or Niacinum has to be carefully weighed.
At the accompanying therapy of a fibratama Rozulip's reception in a dose of 40 mg is contraindicated.
Rozulip it is not necessary to use for treatment of patients with the acute, serious violations demonstrating development of a myopathy or contributing with factors to development of a renal failure secondary in relation to a rhabdomyolysis (for example, sepsis, hypotension, extensive surgical intervention, an injury, heavy metabolic, endocrine or electrolytic disturbances, not stopped spasms).
Influence on function of a liver
As well as other inhibitors of HMG-CoA-reductase, Rozulip it is necessary to use with care at treatment of the persons abusing alcoholic beverages and patients with initial pathology of a liver.
Prior to therapy and in 3 months after the beginning of therapy it is recommended to carry out assessment of functional hepatic trials. If the level of transaminases in blood serum exceeds the upper bound of norm more than by 3 times, Rozulip's reception it is necessary to stop or lower his dose. In the post-marketing period the serious undesirable phenomena from a liver (generally the increased level of transaminases in blood serum) were more often observed at patients who received drug in a dose of 40 mg.
At patients with a hypercholesterolemia owing to a hypothyroidism or a lipoid nephrosis therapy of basic diseases has to be carried out prior to treatment by Rozulip.
Race
Results of pharmacokinetic researches demonstrate that at persons of Asian race Rozulip's bioavailability is higher, than at persons of white Caucasian race.
Inhibitors of proteases
Therapy by Rozulip in combination with inhibitors of proteases is not recommended.
An interstitial disease of lungs
Very exceptional cases of an interstitial disease of lungs were registered at the patients receiving some drugs from group of statines. As a rule, these cases were observed at long-term therapy by statines. The interstitial disease of lungs is shown by short wind, unproductive cough and deterioration in the general state (increased fatigue, decrease in body weight and fever). If there are suspicions on development in the patient of an interstitial disease of lungs, therapy by statines it is necessary to stop.
The lactose intolerance
is not recommended to take the Drug to patients with rare hereditary intolerance of a galactose, insufficiency of lactase and a sprue of glucose and a galactose.
One tablet, coated 10 mg - contains 121.2 mg of lactose of monohydrate, in a tablet of 20 mg - 242.4 mg of lactose of monohydrate, in a tablet of 40 mg - 484.8 mg of lactose of monohydrate.
Use in pediatrics
is not recommended to use Drug at children and teenagers aged up to 10 years due to the lack of data on its safety and efficiency of use.
Pregnancy and feeding by a breast
Rozulip is contraindicated during pregnancy and in the period of a lactation.
Women of childbearing age have to use effective measures of contraception. As cholesterol and other products of biosynthesis of cholesterol are necessary for normal fetation, the potential risk of suppression of activity of HMG-CoA-reductase exceeds advantages of therapy by drug during pregnancy. If pregnancy occurred against the background of therapy by Rozulip, then administration of drug needs to be stopped immediately. Data on excretion of rosuvastatin with breast milk are absent.
The features of influence of medicine on ability of control of vehicles and potentially dangerous mechanisms
of the Research estimating Rozulip's influence on ability to control of vehicles and mechanisms were not carried out. During the driving or work with potentially dangerous mechanisms it is necessary to consider that during therapy there can be dizziness.
Overdose
Symptoms – strengthening of expressiveness of symptoms of side effects.
Treatment: in case of overdose it is necessary to carry out symptomatic treatment, besides, it is necessary to control function of a liver and level of a creatine kinase in blood serum. Specific antidote for rosuvastatin does not exist. The efficiency of a hemodialysis is improbable.
A form of release and packing
On 7 tablets in blister strip packaging from the combined film of 'cold' (polyamide / aluminum foil / a polyvinylchloride film (PVC) and aluminum foil. On 2, 4 or 8 blister strip packagings together with the instruction for medical use in the state and Russian languages place in a cardboard pack.
3 years
not to use a period of storage after expiry date.
To Store storage conditions at a temperature not above 25 °C.
To store out of children's reach!
BUDAPEST JSC EGIS PHARMATSEVTICHESKY PLANT Producer 1106, Keresturi St., 30-38 Hungary
to Develop prescription status According to the prescription
the Trade name
of Rozulip®
the International unlicensed
name Rosuvastatin Dosage Form
of the Tablet, coated 10 mg, 20 mg, 40 mg
Structure
One tablet contains
active agent - rosuvastatin of 10 mg, 20 mg and 40 mg (10.68 mg, 21.36 mg and 42.72 mg of rosuvastatin of zinc, respectively are equivalent),
excipients: ludipress (lactoses monohydrate, povidone, krospovidon), krospovidon (XL10), magnesium stearate, Opadry II white 85F 18422 (polyvinyl alcohol, titan E 171 dioxide, macrogoal 3350, talc.
The description
White or almost white, round slightly biconvex tablets, coated, without or almost flavourless, with an engraving of the stylized letter E on one party and number 592 – on other party of a tablet (for a dosage of 10 mg).
White or almost white, round slightly biconvex tablets, coated, without or almost flavourless, with an engraving of the stylized letter E and number 593 on one party of a tablet (for a dosage of 20 mg).
White or almost white, oval slightly biconvex tablets, coated, without or almost flavourless, with an engraving of the stylized letter E and number 594 on one party of a tablet (for a dosage of 40 mg).
Pharmacotherapeutic group
Hypolipidemic drugs. Reductase HMG-CoA inhibitors.
The ATX C10A A07 code
the Pharmacological
Pharmacokinetics Maximum Concentration properties of rosuvastatin in blood plasma is reached approximately in 5 hours after oral administration. The absolute bioavailability is about 20%. Rosuvastatin is absorbed, mainly, by a liver where there is the main synthesis of cholesterol and removal of Hs-LPNP. The volume of distribution of rosuvastatin is about 134 l. About 90% of rosuvastatin contact proteins of plasma, mainly albumine. Rosuvastatin in insignificant degree is exposed to metabolism (about 10%). Rosuvastatin is non-core substrate for isoenzymes of a system of P450 cytochrome. The main enzyme participating in rosuvastatin metabolism is CYP2C9. CYP2C19, CYP3A4 and CYP2D6 enzymes are involved in metabolism to a lesser extent. The main derivatives of rosuvastatin are N-desmetil and lactonic metabolites. N-desmetil for about 50% is less active, than rosuvastatin, lactonic derivatives are pharmacological not active. Rosuvastatin provides suppression of activity of more than 90% of the circulating HMG-CoA-reductase. About 90% of a dose of rosuvastatin are removed in not changed view with excrements (including the absorbed and not absorbed rosuvastatin). The rest of a dose is removed with urine. About 5% of a dose of drug are excreted with urine in not changed state. Elimination half-life of drug makes about 19 hours of blood plasma. Elimination half-life does not change at increase in a dose of drug. The average geometrical plasma clearance is about 50 liters/hour (coefficient of variation of 21.7%). Similar to other HMG-CoA-reductases inhibitors, in the course of hepatic capture of rosuvastatin the membrane protein carrier of organic anions like C (OATP-C) which is carrying out an important role in hepatic elimination of Rozulip participates. The system bioavailability of rosuvastatin increases in proportion to a dose. When using drug several times in day the pharmacokinetic parameters do not change.
As well as in case of other HMG-CoA-reductases inhibitors, the membrane carrier of cholesterol who is carrying out an important role in hepatic elimination of Rozulip is involved in process of hepatic capture of rosuvastatin.
System exposure of rosuvastatin increases in proportion to a dose.
Special groups of patients
Age and sex: Clinically significant influence of age and sex on pharmacokinetic properties of rosuvastatin was not noted. The rosuvastatin pharmacokinetics at use for children and teenagers with a family heterozygous hypercholesterolemia was similar to pharmacokinetics of adult patients.
Race: Results of pharmacokinetic researches demonstrate that in comparison with persons of white Caucasian race, at persons of Asian race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) average area under a curve concentration time (area under the curve, AUC) and the maximum concentration of drug in blood plasma (Cmax) is approximately twice higher. At Hindus these indicators are approximately 1.3 times higher, than at persons of white race. The analysis of population pharmacokinetics did not reveal clinically significant differences in pharmacokinetic parameters of rosuvastatin between persons of white and negroid race.
Patients with a renal failure. The slight or moderate renal failure did not influence concentration of rosuvastatin or a N-desmetil-metabolite in blood plasma. At patients with a heavy renal failure (clearance of creatinine
the Pharmacodynamics
Rozulip – a selection, competitive inhibitor of HMG-CoA-reductase – the enzyme catalyzing transformation of 3-hydroxy-3-methylglutaryl-coenzyme A in mevalonat, the predecessor of cholesterol. The main target of effect of rosuvastatin is the liver where synthesis of cholesterol (XC) and catabolism of lipoproteins of the low density (LDL) is carried out.
Rosuvastatin increases the number of hepatic receptors of LDL by surfaces of cells at the expense of what capture and catabolism of LDL amplifies and synthesis of lipoproteids of very low density (LPONP) in a liver is suppressed. As a result the total number of LPONP and LDL decreases.
Rozulip reduces the increased content of LDL cholesterol (Hs-LPNP), the general cholesterol and triglycerides (TG), increases the level of cholesterol of lipoproteids of the high density (Hs-LPVP) and also reduces apolipoprotein B content (ApoV), cholesterol NELPVP (Hs-neLPVP), LPONP cholesterol (Hs-LPONP), LPONP (TG-LPONP) triglycerides and increases the content of A-I apolipoprotein (ApoA-I), reduces a ratio of Hs-LPNP/Hs-LPVP, the general cholesterol / Hs-LPVP, Hs-neLPVP/Hs-LPVP and ApoV/ApoA-I. (see Table 1).
Table 1. Effects of various doses of drug at treatment of patients with primary hypercholesterolemia (IIa and IIb type) (the corrected average percentage changes in comparison with initial level)
the Dose
of N Hs-LPNP Obshchy
ApoAI ApoV Hs-LPVP Triglitseridy Hs-neLPVP cholesterol
of Placebo
of 13 - 7 - 5 3 - 3 - 7 - 3 0 5
mg 17 - 45 - 33 13 - 35 - 44 - 38 4 10 mg 17 - 52 - 36 14 - 10 - 48 - 42 4 20 mg 17 - 55 - 40 8 - 23 - 51 - 46 5 40 mg
18
-
63 - 46 10 - 28 - 60 - 54 0
The therapeutic effect is shown within one week after the beginning of therapy by drug, in 2 weeks of treatment reaches 90% of the greatest possible effect. The maximum therapeutic effect is usually reached by 4th week and maintained at regular reception.
Rozulip is effective at treatment of most of patients with a hypercholesterolemia of IIa and IIb of type (average Hs-LPNP initial level is about 4.8 mmol/l) and corresponds to the target indicators provided in the recommendations of the European society of studying atherosclerosis (European Atherosclerosis Society, EAS, 1998). About 80% of the patients taking the drug in a dose of 10 mg reached the target Hs-LPNP level (
Indications
- primary hypercholesterolemia (type II and: hereditary defect ApoV, an autosomal and recessive hypercholesterolemia, an autosomal and prepotent hypercholesterolemia, a sitosterolemiya, a polygenic hypercholesterolemia) or the mixed dislipidemiya (IIb type) as addition to a diet, in cases when correction of food and other non-drug methods of treatment (for example, physical exercises, decrease in body weight) are insufficiently effective
- treatment of a homozygous hereditary hypercholesterolemia as addition to a diet and other methods of treatment directed to decrease in level of lipids in blood (for example, LPNP-aferez) and also in cases when these methods are insufficiently effective
- prevention of the undesirable cardiovascular phenomena at patients, with a high probability of predisposition to the first cardiovascular phenomenon as addition to correction of other risk factors
- treatment of atherosclerosis at the patients needing lipidosnizhayushchy treatment for delay of progressing of a disease.
The route of administration and doses
use Drug strictly on doctor's orders!
Rozulip it is possible to accept at any time, irrespective of meal. Prior to the beginning of and during all course of therapy by Rozulip the patient has to keep to a standard diet with the low content of cholesterol. The dose of drug should be selected individually, depending on the purposes of therapy and the response to treatment.
The recommended initial dose of drug for the patients receiving therapy by other HMG-CoA-reductases inhibitor and also for persons who did not accept before statines makes 5 or 10 mg once a day. When choosing an initial dose it is necessary to be guided by the level of content of cholesterol and to take possible risk of cardiovascular complications into account and also it is necessary to estimate potential risk of development of side effects. In case of need, the dose can be increased after 4 weeks of administration of drug.
Due to the possible development of side effects at reception of a dose of 40 mg, increase in a dose to the maximum 40 mg can be considered only at patients with a heavy hypercholesterolemia and with high risk of cardiovascular complications (especially at a hereditary hypercholesterolemia) at which the desirable result of therapy at reception of a dose of 20 mg was not achieved. Observation of the patients receiving drug in a dose of 40 mg is recommended. And also, it is recommended to begin therapy with the drug Rozulip in a dose of 40 mg under control of the doctor.
Use for children and teenagers
Use for children and teenagers has to be carried out only under control of the expert.
Children and teenagers from 10 to 17 years (boys at Tanner II'S stage above, girls at least in a year after the beginning of a menstrual cycle):
For children and teenagers with a heterozygous family hypercholesterolemia the usual initial dose makes 5 mg a day. Usual range of doses – 5-20mg in day orally. According to the recommendations of use in pediatrics, increase in a dose has to be carried out depending on the individual answer and shipping of patients. Prior to treatment by rosuvastatin children and teenagers should appoint a standard holestirinoponizhayushchy diet which should be observed also during treatment. Safety and efficiency of the doses exceeding 20 mg for this group of patients it was not studied.
Tablets of 40 mg should not be applied to treatment of the patients who did not reach 17 years.
Experience of use of drug for children aged up to 10 years (aged from 8 up to 10 years) suffering from a homozygous hereditary hypercholesterolemia is limited. Therefore treatment by rosuvastatin of children aged up to 10 years is not recommended.
Elderly patients
dose adjustment is not required. The recommended initial dose of drug for patients is more senior than 70 years makes 5 mg.
Patients with a renal failure
with a renal failure easy or moderate severity dose adjustment is not required From patients. At patients with moderate renal failures (the clearance of creatinine
Patients with a liver failure
Is absent experience of use of drug for patients with assessment higher than 9 points on Child-Pugh scale. Nevertheless, at patients with assessment of 8 and 9 balls on a scale of Child-Pugh the increase in system bioavailability was observed. The drug Rozulip is contraindicated to patients with liver diseases in an active phase.
The race
the Increased system bioavailability of drug was registered at patients of Asian race. For persons of Asian origin the recommended initial dose of drug makes 5 mg. Therapy by Rozulip in a dose of 40 mg is contraindicated to patients of this group.
The patients predisposed to a myopathy
prescribing of drug in a dose of 40 mg is contraindicated to patients with the factors predisposed to development of a myopathy the Recommended initial dose for this group of patients makes 5 mg.
Side effects
Often (from> 1/100 to
- a headache, dizziness
- a constipation, nausea, an abdominal pain
- myalgia
- an asthenia
- sugar diabet1
Infrequently (from> 1/1000 to
- an itching, rash, urticaria
Seldom (from> 1/10000 to
- reactions of hypersensitivity, including a Quincke's disease
- a myopathy (including a miositis) and a rhabdomyolysis
- increase in level of hepatic transaminases in blood serum, pancreatitis
Very seldom (
-polyneuropathy
- memory loss
- jaundice, hepatitis
- an arthralgia
- a hamaturia
- a gynecomastia
Frequency is unknown (it is impossible to define proceeding from available data)
- cough, short wind
- diarrhea
- Stephens-Johnson's syndrome
- hypostasis
- interstitial diseases of lungs
As well as at use of other HMG-CoA-reductases inhibitors, the frequency of emergence of side effects has dose-dependent character.
At some patients taking the drug the dose-dependent increase in concentration of a creatine kinase was revealed. In most cases, this phenomenon had easy, asymptomatic and passing temper. At the increased concentration of a creatine kinase in blood serum (more than by 5 times in comparison with VGN) therapy by Rozulip should be stopped.
As well as in case of intake of other HMG-CoA-reductases inhibitors, at a small amount of the patients accepting Rozulip the dose-dependent increase in content of transaminases in blood serum which in most cases, had easy, asymptomatic and passing temper was observed.
Against the background of therapy some statines registered the following by-effects: sleep disorders, including insomnia and dreadful dreams, disturbances of sexual function, the depression, very exceptional cases of an interstitial disease of lungs registered generally at long-term therapy by statines.
Frequency of development of a rhabdomyolysis, the profound renal failures and serious violations from a liver (which are generally given by increase in concentration of transaminases) above when using drug in a dose of 40 mg.
1 Frequency of cases of diabetes will depend on existence or lack of risk factors (a glucose indicator on an empty stomach ≥ 5.6 mmol/l, body mass index> 30kg/sq.m, increase in level of triglycerides, the increased arterial blood pressure).
At the patients accepting rosuvastatin the proteinuria, in most cases canalicular on a proiskhozhdeniiya, determined by the test by means of an indicator strip was observed. Changes in protein of urine from its total absence or a small amount to ++ or it was more observed at 1% of patients during treatment by a dosage of 10 mg or 20 mg and approximately at 3% of the patients accepting a dose of 40 mg. Small increase from total absence or a small amount to + was observed at reception of a dose of 20 mg. In most cases at continuous treatment the proteinuria decreased or disappeared. On the basis of information obtained during clinical trials, and post-registration experience the lack of interrelation between a proteinuria and the acute or progressing renal failure is till today established.
Increase in level of a creatine kinase in 10 times more of the upper bound of norm and also the muscular symptoms following exercises or the increased physical activity were observed more often during 52-hnedelny clinical trial of children and teenagers, in comparison with adults. On other indicators the results of a research of safety of rosuvastatin at children, teenagers and adults match.
Contraindications
- hypersensitivity to rosuvastatin or any of drug components
- liver diseases in an active phase, including permanent increase
in concentration of transaminases in blood serum and any increase in activity of transaminases in blood serum (more than by 3 times in comparison with the upper bound of norm)
- the profound renal failures (clearance of creatinine
- a myopathy, predisposition to development of miotoksichesky complications
- a concomitant use of cyclosporine
- pregnancy and the period of a lactation
-use for women of reproductive age who do not use
effective methods of contraception
- children's age up to 10 years
the Therapy by the drug Rozulip in a dose of 40 mg is contraindicated:
To patients with the factors contributing to development of a myopathy (rhabdomyolysis):
- a renal failure of moderate severity (clearance of creatinine
- a hypothyroidism
- muscular diseases in the anamnesis
- the myopathy connected with intake of other HMG-CoA inhibitors - reductase or fibrat in the anamnesis
- an alcohol abuse
- states which can lead to increase in plasma
concentration of rosuvastatin
- patients of Asian race
- a concomitant use of fibrat
- children and teenagers up to 17 years
Medicinal interactions
Cyclosporine. At simultaneous use with Rozulip, indicators of AUC rosuvastatin were about 7 times higher, than at monotherapy by drug at healthy faces. Simultaneous use of rosuvastatin and cyclosporine does not affect plasma concentration of cyclosporine.
Antagonists of vitamin K. As well as in case of therapy by other HMG-CoA-reductases inhibitors, the beginning of therapy or increase in a dose of Rozulip at the patients receiving at the same time antagonists of vitamin K (for example, warfarin or other anticoagulants derivative coumarin), can be followed by increase in the international normalized relation (INR). After the termination of reception of Rozulip or decrease in its dose, MNO can decrease. In such cases the monitoring of MNO is recommended.
Gemfibrozil and other drugs reducing the maintenance of lipids in blood. Gemfibrozit simultaneous use and Rozulipa was followed by double increase in Cmax and AUC rosuvastatin. Based on data on specific interaction, significant interaction with fenofibraty, perhaps pharmakodinamichesky interaction is not expected pharmacokinetically. Gemfibrozil, fenofibrat, other fibrata and also Niacinum (niacin) in the doses reducing the maintenance of lipids in blood (1 g/day or more), increase risk of development of a myopathy at simultaneous use with HMG-CoA-reductases inhibitors, it is possible because they can cause a myopathy and when using as monotherapy. Therapy by Rozulip in a dose of 40 mg is contraindicated at the accompanying use of fibrat. At the accompanying therapy from fibrata the recommended initial dose of rosuvastatin has to make 5 mg.
Ezetimib. At simultaneous use with Rozulip the changes of AUC or Cmax of these drugs did not note. Nevertheless, between Rozulip and ezetimiby it is impossible to exclude pharmakodinamichesky interaction with development of side effects.
Inhibitors of proteases. In spite of the fact that the exact mechanism of interaction is unknown, simultaneous use of inhibitors of proteolytic enzymes can lead to significant increase in bioavailability of rosuvastatin. According to results of a pharmacokinetic research at simultaneous use of Rozulip in a dose of 20 mg and the combined drug of inhibitors of proteases (400 mg lopinavira/100 the mg of a ritonavir) at healthy volunteers noted increase in AUC0-24 and Cmax of rosuvastatin in an equilibrium state, respectively, in 2 and 5 times. Therefore the concomitant use of rosuvastatin and inhibitors of proteases at treatment of patients with HIV is not recommended.
Antacids. Simultaneous use of Rozulip and the suspension of an antacid containing aluminum and magnesium hydroxide was followed by decrease in concentration of rosuvastatin in blood plasma approximately for 50%. This effect decreased if patients accepted an antacid in 2 hours after Rozulip. The clinical importance of this interaction is not established.
Erythromycin. Simultaneous use of Rozulip and erythromycin was characterized by reduction of AUC0-t and Cmax of rosuvastatin, respectively, for 20 and 30%.
Oral contraceptives / gormonozamestitelny therapy (ZGT). Simultaneous use of Rozulip and oral contraceptives was followed by increase in AUC ethinylestradiol and Norgestrelum by 26 and 34%, respectively Increase in concentration of these hormones in blood plasma needs to be considered at selection of doses of oral contraceptives. The pharmacokinetic data characterizing Rozulip's use against the background of ZGT are absent therefore it is impossible to exclude development of the effects similar to above. However, such therapy was widely performed within clinical trials and differed in good tolerance in patients.
Digoxin. Clinically significant interaction of Rozulip and digoxin is improbable.
P450 cytochrome enzymes. Rosuvastatin is not inhibitor or the inductor of isoenzymes of a system of P450 cytochrome. Besides, rosuvastatin – non-core substrate for these isoenzymes. Between rosuvastatin and flukonazoly (CYP2C9 and CYP3A4 inhibitor) or ketokonazoly (CYP2A6 and CYP3A4 inhibitor) clinically significant interaction was not observed. The accompanying Rozulip's use and an itrakonazola (CYP3A4 inhibitor) was followed by increase in AUC rosuvastatin by 28%. Such changes are not considered as clinically significant. Thus, the medicinal interaction connected with the drug metabolism mediated by isoenzymes of a system of P450 cytochrome is improbable.
Special instructions
Influence on function of kidneys
At some patients accepting Rozulip (especially in a dose of 40 mg), the proteinuria was observed. The proteinuria was diagnosed in the analysis of urine by means of indicator strips. In most cases, it had canalicular origin, had passing or intermittent character. Changes of protein content from total absence and traces to ++ or were more observed less than at 1% of the patients receiving drug in a dose of 10 or 20 mg and also approximately at 3% of the patients taking the drug in a dose of 40 mg. The minimum changes of protein content in urine from total absence and traces to + were found in the patients taking the drug in a dose of 20 mg. In most cases the proteinuria decreases or disappears in the course of therapy and does not mean emergence sharp or progressing of the existing disease of kidneys. Within standard inspection of the patients receiving drug in this dose it is necessary to carry out assessment of function of kidneys.
Influence on skeletal muscles
By-effects from skeletal muscles (for example, myalgia, a myopathy (including mozit), and, in rare instances, a rhabdomyolysis with an acute renal failure or without it) were observed at the patients taking the drug in any doses, especially often in the doses exceeding 20 mg. Very seldom the rhabdomyolysis developed at the accompanying therapy ezetimiby and HMG-CoA-reductases inhibitors. At simultaneous use of these drugs it is impossible to exclude pharmakodinamichesky interaction and it is necessary to be careful.
As well as in case of therapy by other HMG-CoA inhibitors - reductases, the frequency of development of a rhabdomyolysis, the profound renal failures and serious violations from a liver (which are generally given by increase in concentration of transaminases) above when using drug in a dose of 40 mg.
Definition of concentration of a creatine kinase
Determination of level of a creatine kinase in blood serum should not be carried out after intensive physical activity or in the presence of other possible reasons of increase in concentration of a creatine kinase as it can complicate interpretation of results. If the initial level of a creatine kinase is considerably increased (5 times higher, than the upper bound of norm), in 5 - 7 days it is necessary to take repeated measurement. It is not necessary to begin therapy if the repeated test confirms the initial level of a creatine kinase (more than 5 times higher in comparison with the upper bound of norm).
Prior to therapy
As well as other inhibitors of HMG-CoA-reductase, Rozulip patients need to appoint with care with the factors contributing to development of a myopathy (rhabdomyolysis): the renal failure, a hypothyroidism, hereditary pathology of a muscular system at the patient or his immediate family, the myopathy connected with intake of other HMG-CoA inhibitor - reductase or the fibrat in the anamnesis, an alcohol abuse, age is more senior than 70 years, situations at which increase in concentration of rosuvastatin in blood plasma, the accompanying use of fibrat can be observed.
When prescribing drug such patients need to weigh carefully potential risk of therapy and possible advantage. Besides, it is recommended to carry out clinical monitoring.
During therapy
the doctor Should inform the patient on need of the immediate message about cases of unexpected appearance of muscular pains, muscle weakness or spasms, especially if they are followed by an indisposition and fever. At such patients it is necessary to determine creatine kinase level in blood serum. Therapy has to be stopped if the level of a creatine kinase is considerably increased (more than by 5 times in comparison with the upper bound of norm) or if symptoms from muscles are pronounced and cause daily discomfort (even if the level of a creatine kinase is 5 times less in comparison with the upper bound of norm). If symptoms disappear and the level of a creatine kinase returns to norm, it is necessary to consider a question of repeated appointment of Rozulip or other HMG-CoA-reductases inhibitors in smaller doses at careful observation of the patient. Routine control of a creatine kinase in the absence of symptoms is not reasonable.
Signs of increase in impact on skeletal muscles at Rozulip's reception and the accompanying therapy are noted. It was reported about increase in cases of a miositis and a myopathy at the patients accepting other inhibitors of HMG-CoA-reductase in combination with derivatives of fibrinous acid, including gemfibrozit, cyclosporine, niacin, azolny antifungal means, inhibitors of proteases and makrolidny antibiotics. Gemfibrozil increases risk of emergence of a myopathy at the combined appointment with some HMG-CoA inhibitors - reductases. Thus, co-administration of Rozulip and a gemfibrozil is not recommended. The ratio of risk and possible advantage at combined use of Rozulip and fibrat or Niacinum has to be carefully weighed.
At the accompanying therapy of a fibratama Rozulip's reception in a dose of 40 mg is contraindicated.
Rozulip it is not necessary to use for treatment of patients with the acute, serious violations demonstrating development of a myopathy or contributing with factors to development of a renal failure secondary in relation to a rhabdomyolysis (for example, sepsis, hypotension, extensive surgical intervention, an injury, heavy metabolic, endocrine or electrolytic disturbances, not stopped spasms).
Influence on function of a liver
As well as other inhibitors of HMG-CoA-reductase, Rozulip it is necessary to use with care at treatment of the persons abusing alcoholic beverages and patients with initial pathology of a liver.
Prior to therapy and in 3 months after the beginning of therapy it is recommended to carry out assessment of functional hepatic trials. If the level of transaminases in blood serum exceeds the upper bound of norm more than by 3 times, Rozulip's reception it is necessary to stop or lower his dose. In the post-marketing period the serious undesirable phenomena from a liver (generally the increased level of transaminases in blood serum) were more often observed at patients who received drug in a dose of 40 mg.
At patients with a hypercholesterolemia owing to a hypothyroidism or a lipoid nephrosis therapy of basic diseases has to be carried out prior to treatment by Rozulip.
Race
Results of pharmacokinetic researches demonstrate that at persons of Asian race Rozulip's bioavailability is higher, than at persons of white Caucasian race.
Inhibitors of proteases
Therapy by Rozulip in combination with inhibitors of proteases is not recommended.
An interstitial disease of lungs
Very exceptional cases of an interstitial disease of lungs were registered at the patients receiving some drugs from group of statines. As a rule, these cases were observed at long-term therapy by statines. The interstitial disease of lungs is shown by short wind, unproductive cough and deterioration in the general state (increased fatigue, decrease in body weight and fever). If there are suspicions on development in the patient of an interstitial disease of lungs, therapy by statines it is necessary to stop.
The lactose intolerance
is not recommended to take the Drug to patients with rare hereditary intolerance of a galactose, insufficiency of lactase and a sprue of glucose and a galactose.
One tablet, coated 10 mg - contains 121.2 mg of lactose of monohydrate, in a tablet of 20 mg - 242.4 mg of lactose of monohydrate, in a tablet of 40 mg - 484.8 mg of lactose of monohydrate.
Use in pediatrics
is not recommended to use Drug at children and teenagers aged up to 10 years due to the lack of data on its safety and efficiency of use.
Pregnancy and feeding by a breast
Rozulip is contraindicated during pregnancy and in the period of a lactation.
Women of childbearing age have to use effective measures of contraception. As cholesterol and other products of biosynthesis of cholesterol are necessary for normal fetation, the potential risk of suppression of activity of HMG-CoA-reductase exceeds advantages of therapy by drug during pregnancy. If pregnancy occurred against the background of therapy by Rozulip, then administration of drug needs to be stopped immediately. Data on excretion of rosuvastatin with breast milk are absent.
The features of influence of medicine on ability of control of vehicles and potentially dangerous mechanisms
of the Research estimating Rozulip's influence on ability to control of vehicles and mechanisms were not carried out. During the driving or work with potentially dangerous mechanisms it is necessary to consider that during therapy there can be dizziness.
Overdose
Symptoms – strengthening of expressiveness of symptoms of side effects.
Treatment: in case of overdose it is necessary to carry out symptomatic treatment, besides, it is necessary to control function of a liver and level of a creatine kinase in blood serum. Specific antidote for rosuvastatin does not exist. The efficiency of a hemodialysis is improbable.
A form of release and packing
On 7 tablets in blister strip packaging from the combined film of 'cold' (polyamide / aluminum foil / a polyvinylchloride film (PVC) and aluminum foil. On 2, 4 or 8 blister strip packagings together with the instruction for medical use in the state and Russian languages place in a cardboard pack.
3 years
not to use a period of storage after expiry date.
To Store storage conditions at a temperature not above 25 °C.
To store out of children's reach!
BUDAPEST JSC EGIS PHARMATSEVTICHESKY PLANT Producer 1106, Keresturi St., 30-38 Hungary
to Develop prescription status According to the prescription
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