Krestor of 20 mg

General characteristics. Structure:

Active agent: a rozuvastatina of 10, 20 or 40 mg in the form of a rozuvastatin of calcium.
Excipients: lactoses monohydrate of 89,50 mg (for a dosage of 10 mg), 179,00 (for a dosage of 20 mg), 164,72 mg (for a dosage of 40 mg); cellulose of microcrystallic 29,82 mg (for a dosage of 10 mg), 59,64 mg (for a dosage of 20 mg), 54,92 mg (for a dosage of 40 mg); calcium phosphate of 10,90 mg (for a dosage of 10 mg), 21,80 mg (for a dosage of 20 mg), 20,00 mg (for a dosage of 40 mg); кросповидон 7,50 mg (for a dosage of 10 mg), 15,00 mg (for a dosage of 20 mg), 15,00 mg (for a dosage of 40 mg); magnesium stearate of 1,88 mg (for a dosage of 10 mg), 3,76 mg (for a dosage of 20 mg), 3,76 mg (for a dosage of 40 mg); tablet cover: lactoses monohydrate of 1,80 mg (for a dosage of 10 mg), 3,60 mg (for a dosage of 20 mg), 3,60 mg (for a dosage of 40 mg); gipromelloza of 1,26 mg (for a dosage of 10 mg), 2,52 mg (for a dosage of 20 mg), 2,52 mg (for a dosage of 40 mg), triacetin (glycerin triacetate) 0,36 mg (for a dosage of 10 mg), 0,72 mg (for a dosage of 20 mg), 0,72 mg (for a dosage of 40 mg); titanium dioxide of 1,06 mg (for a dosage of 10 mg), 2,11 mg (for a dosage of 20 mg), 2,11 mg (for a dosage of 40 mg); dye ferrous oxide of red 0,02 mg (for a dosage of 10 mg), 0,05 mg (for a dosage of 20 mg), 0,05 mg (for a dosage of 40 mg).
Description
Tablets of 10 mg: round, biconvex tablets, film coated pink color, with an engraving of "ZD4522 10" on one party.
Tablets of 20 mg: round biconvex tablets, film coated pink color, with an engraving of "ZD4522 20" on one party.
Tablets of 40 mg: oval, biconvex tablets, film coated pink color, with an engraving of "ZD4522" on one party and 40 - on another.

Pharmacological properties:

Action mechanism
Rozuvastatin is the selection, competitive inhibitor of HMG-CoA reductase, the enzyme turning 3-hydroxy-3-methylglutaryl coenzyme A in мевалонат, the predecessor of cholesterol. The main target of action of a rozuvastatin is the liver where synthesis of cholesterol (XC) and a catabolism of lipoproteins of the low density (LPNP) is carried out.
Rozuvastatin increases number of "hepatic" receptors of LPNP by surfaces of cells, increasing capture and a catabolism of LPNP that in turn leads to inhibition of synthesis of lipoproteins of very low density (LPONP), reducing thereby total quantity of LPNP and LPONP.

Pharmacodynamics. Крестор® reduces the increased concentration holesterina-LPNP (HS-LPNP), the general cholesterol, triglycerides (TG), increases concentration of cholesterol lipoproteins of the high density (HS-LPVP), and also reduces concentration of apolipoprotein B (Apov), HS-NELPVP, HS-LPONP, TG-LPONP also increases concentration of A-I apolipoprotein (Apoa-I) (see tables 1 and 2), reduces a ratio of HS-LPNP/HS-LPVP, the general HS/HS-LPVP and HS-NELPVP/HS-LPVP and a ratio of Apob/Apoa-I.
The therapeutic effect develops within one week after the beginning of therapy by the drug Krestor®, in 2 weeks of treatment reaches 90% of the greatest possible effect. The maximum therapeutic effect is usually reached by 4th week of therapy and supported at regular administration of drug.
Table 1. Dozozavisimy effect at patients with primary hypercholesterolemia (the IIa and IIb type across Fredrikson) (the average corrected percentage change in comparison with a reference value).

Dose           Quantity           of HS-          General                          HS-TG HS-NELPVP      Apo of B    Apo of A-I
                   patients                         of LPNP XC LPVP  
                        Placebo 13 - 7            -                           5 3-3           -                     7 - 3            0
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

Table 2. Dozozavisimy effect at patients with a gipertriglitseridemiya (the IIb and IV type across Fredrikson) (average percentage change in comparison with a reference value).

Dose           Quantity                   of TG HS-          General      HS-                               HS-NELPVP HS-TG-
                   patients                                                                          of LPNP XC LPVP LPONP LPONP
                                                                                                                    Placebo 26 1 5 1-3 2 2 6
10 mg                            23 - 37         -           45 - 40                        8 - 49                  -                48 - 39
20 mg                           27 - 37         -                                  31 - 34 22 - 43                  -                49 - 40
40 mg                           25 - 43         -                                   43 - 40 17 - 51                  -                56 - 48

Clinical performance
Крестор® it is effective at adult patients with a hypercholesterolemia with or without gipertriglitseridemiya, regardless of race, a floor or age, including, at patients with a diabetes mellitus and a family hypercholesterolemia.
At 80% of patients with a hypercholesterolemia of IIa and IIb of type across Fredrikson (average initial concentration of HS-LPNP about 4,8 mmol/l) against the background of administration of drug in a dose of 10 mg concentration of HS-LPNP reaches values less than 3 mmol/l.
At the patients with a heterozygous family hypercholesterolemia receiving Krestor® in a dose of 20-80 mg positive dynamics of indicators of a lipidic profile is noted (a research with participation of 435 patients). After titration to a daily dose of 40 mg (12 weeks of therapy), decrease in concentration is noted
HS-LPNP for 53%. At 33% of patients concentration of HS-LPNP less than 3 mmol/l is reached.
At the patients with a homozygous family hypercholesterolemia accepting Krestor® in a dose of 20 mg and 40 mg, average decrease in concentration of HS-LPNP makes 22%.
Patients with a gipertriglitseridemiya with initial concentration of TG have from 273 to 817 mg/dl receiving Krestor® in a dose from 5 mg to 40 mg once a day within 6 weeks, concentration of TG in a blood plasma considerably decreased (see table 2).
The additive effect is noted in a combination with fenofibraty concerning concentration of triglycerides and with niacin in lipidsnizhayushchy doses concerning concentration of HS-LPVP (see also section "Special Instructions").
In the research METEOR with participation of 984 patients at the age of 45 – 70 years with low risk of development of the coronary heart disease (CHD) (10-year risk on the Framingemsky scale less than 10%), average concentration of the XC LPNP of 4,0 mmol/l (154,5 mg/dl) and subclinical atherosclerosis (which was estimated on thickness of a complex of "erotic media" of carotid arteries – TKIM) studied influence of a rozuvastatin on thickness of a complex of "erotic media".
Patients received розувастатин in a dose 40 mg/days or placebo within 2 years. Therapy rozuvastatiny considerably slowed down the speed of progressing of the maximum TKIM for 12 segments of a carotid artery in comparison with placebo with distinction on –0,0145 mm/year [95% a confidence interval from –0,0196 to – 0,0093; р <0,001]. In comparison with reference values in group of a rozuvastatin reduction of the TKIM maximum value by 0,0014 mm/year (0,12%/year (doubtful distinction)) in comparison with increase in this indicator by 0,0131 mm/year (1,12%/year (р <0,001)) in group of placebo was noted. So far to direct dependence between reduction of TKIM and decrease in risk of cardiovascular events it was not shown. The research METEOR was conducted at patients with low risk of an ischemic heart disease for which the dose of the drug Крестор® 40 of mg is not recommended. The dose of 40 mg has to be applied at patients with the expressed hypercholesterolemia and high risk of the cardiovascular diseases (CD).
Results of the conducted research JUPITER (Justification of use of statines for primary prevention: an intervention research on assessment of a rozuvastatin) at 17802 patients showed that розувастатин the risk of development of cardiovascular complications (252 in group of placebo in comparison with 142 in group of a rozuvastatin) (р <0,001) with decrease in relative risk by 44% significantly reduced. Efficiency of therapy was noted in 6 first months of use of drug. Statistically significant decrease by 48% of the combined criterion including death from the cardiovascular reasons, a stroke and a myocardial infarction is noted (a ratio of risks: 0,52, 95%, confidence interval 0,40-0,68, p <0,001), reduction by 54% of developing of a fatal or not fatal myocardial infarction (ratio of risks: 0,46, 95%, a confidence interval 0,30-0,70) and for 48% - a fatal or not fatal stroke. The general mortality decreased by 20% in group of a rozuvastatin (a ratio of risks: 0,80, 95%, confidence interval 0,67-0,97, р =0,02). The safety profile at the patients accepting розувастатин in a dose of 20 mg, in general, was similar to a safety profile in group of placebo.

Pharmacokinetics. Absorption and distribution
The maximum concentration of a rozuvastatin in a blood plasma is reached approximately in 5 hours after intake. Absolute bioavailability makes about 20%.
Rozuvastatin is metabolized preferential by a liver which is the main place of synthesis of cholesterol and metabolism of HS-LPNP. The volume of distribution of a rozuvastatin makes about 134 l. About 90% of a rozuvastatin contact proteins of a blood plasma, generally albumine.
Metabolism
Is exposed to limited metabolism (about 10%). Rozuvastatin is non-core substrate for metabolism by enzymes of system of P450 cytochrome. The main isoenzyme participating in metabolism of a rozuvastatin is CYP2C9 isoenzyme. Isoenzymes of CYP2C19, CYP3A4 and CYP2D6 are involved in metabolism to a lesser extent.
The main revealed metabolites of a rozuvastatin are N-desmetil and lactonic metabolites. N-desmetil for about 50% is less active, than розувастатин, lactonic metabolites are pharmacological not active. More than 90% of pharmacological activity on inhibition of the circulating HMG-CoA reductase are provided rozuvastatiny, the rest – its metabolites.
Removal
About 90% of a dose of a rozuvastatin are removed in not changed look through intestines (including absorbed and not absorbed розувастатин). The rest is removed by kidneys. The plasma elimination half-life (T ½) makes about 19 hours. The elimination half-life does not change at increase in a dose of drug. The average geometrical plasma clearance makes about 50 l/hour (coefficient of variation of 21,7%). As well as in case of other inhibitors of HMG-CoA reductase, the membrane carrier of cholesterol which is carrying out an important role in hepatic elimination of a rozuvastatin is involved in process of "hepatic" capture of a rozuvastatin.
Linearity
System exposure of a rozuvastatin increases in proportion to a dose. Pharmacokinetic parameters do not change at daily reception.
Special populations of patients. Age and floor
Gender and age do not exert clinically significant impact on pharmacokinetics of a rozuvastatin.
Ethnic groups
Pharmacokinetic researches showed approximately double increase in a median of AUC (the area under a curve "concentration time") and Cmax (the maximum concentration in a blood plasma) a rozuvastatina at patients of an Asian nationality (Japanese, Chinese, Filipinos, Vietnamese and Koreans) in comparison with Europeans; at the Indian patients increase in a median of AUC and Cmax by 1,3 times is shown. The pharmacokinetic analysis did not reveal clinically significant distinctions in pharmacokinetics among Europeans and representatives of negroid race.
Renal failure
At patients with the slight and moderately expressed renal failure the size of plasma concentration of a rozuvastatin or N-desmetila significantly does not change. At patients with the expressed renal failure (the clearance of creatinine (CC) less than 30 ml/min.) concentration of a rozuvastatin in a blood plasma is 3 times higher, and concentration of N-desmetila is 9 times higher, than at healthy
volunteers. Concentration of a rozuvastatin in a blood plasma at patients on a hemodialysis was about 50% higher, than at healthy volunteers.
Liver failure
At patients with various stages of a liver failure increase in an elimination half-life of a rozuvastatin at patients with point 7 and below on a scale of Chayld-Pyyu is not revealed. At two patients with points 8 and 9 on a scale of Chayld-Pyyu increase in an elimination half-life, at least, is noted twice. Experience of use of a rozuvastatin for patients with point higher than 9 on a scale of Chayld-Pyyu is absent.

Indications to use:

Primary hypercholesterolemia across Fredrikson (the IIa type, including a family heterozygous hypercholesterolemia) or the mixed hypercholesterolemia (IIb type) as addition to a diet when the diet and other non-drug methods of treatment (for example, physical exercises, decrease in body weight) are insufficient.
Family homozygous hypercholesterolemia as addition to a diet and other lipidsnizhayushchy therapy (for example, LPNP-aferez), or in cases when similar therapy is insufficiently effective.
Gipertriglitseridemiya (type IV across Fredrikson) as addition to a diet.
For delay of progressing of atherosclerosis as addition to a diet at patients to whom therapy for decrease in concentration of the general in XC and HS-LPNP is shown.
Primary prevention of the main cardiovascular complications (stroke, heart attack, arterial revascularization) at adult patients without clinical signs of an ischemic heart disease, but with the increased risk of its development (the age is more senior than 50 years for men and 60 years for women, the increased concentration of S-reactive protein (≥ 2 mg/l) in the presence are more senior, than at least one of accessory factors of risk, such as arterial hypertension, low concentration of HS-LPVP, smoking, the family anamnesis of the early beginning of an ischemic heart disease).

Route of administration and doses:

Inside, not to chew and not to crush a tablet, to swallow entirely, washing down with water. Drug can be appointed irrespective of meal at any time.
Prior to therapy by the drug Krestor® the patient has to begin to keep to a standard gipokholesterinemichesky diet and to continue to observe it during treatment. The dose of drug has to be selected individually depending on the purposes of therapy and the therapeutic response to treatment, in view of the current recommendations about target concentration of lipids.
The recommended initial dose for the patients beginning to accept drug or for the patients transferred from reception of other inhibitors of HMG-CoA reductase has to make 5 or 10 mg of the drug Крестор® 1 of times a day. At the choice of an initial dose it is necessary to be guided by individual concentration 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 to bigger in 4 weeks (see the section "Pharmacodynamics").
Due to the possible development of side effects at reception of a dose of 40 mg, in comparison with lower doses of drug (see the section "Side effect"), increase in a dose up to 40 mg, after additional reception of a dose is higher than the recommended initial dose within 4 weeks of therapy, can be carried out only at patients with heavy degree of a hypercholesterolemia and with high risk of cardiovascular complications (especially at patients with a family hypercholesterolemia) at which the desirable result of therapy at reception of a dose of 20 mg and which will be under observation of the specialist was not achieved (see the section "Special Instructions"). Especially careful observation of the patients receiving drug in a dose of 40 mg is recommended.
Purpose of a dose of 40 mg is not recommended to the patients who were earlier not seeing a doctor.
After 2-4 weeks of therapy and/or at increase in a dose of the drug Krestor® control of indicators of lipidic exchange is necessary (if necessary dose adjustment is required).
Elderly patients
Dose adjustment is not required.
Patients with a renal failure
With a renal failure easy or moderate severity dose adjustment is not required from patients. At patients with a heavy renal failure (KK less than 30 ml/min.) use of the drug Krestor® is contraindicated. Use of drug in a dose of 40 mg is contraindicated to patients with moderate renal failures (KK less than 30-60 ml/min.) (see the section "Special Instructions" and "Pharmacodynamics"). The initial dose of drug of 5 mg is recommended to patients with moderate renal failures.
Patients with a liver failure
Крестор® it is contraindicated to patients with liver diseases in an active phase (see the section "Contraindications").
Special populations. Ethnic groups
When studying pharmacokinetic parameters of a rozuvastatin at the patients belonging to different ethnic groups increase in system concentration of a rozuvastatin among Japanese and Chinese is noted (see the section "Special Instructions").
It is necessary to consider this fact at purpose of the drug Krestor® to these groups of patients. At purpose of doses of 10 and 20 mg the recommended initial dose for patients of Mongoloid race makes 5 mg. Purpose of drug in a dose of 40 mg is contraindicated to patients of Mongoloid race (see the section "Contraindications").
The patients predisposed to a myopathy
Purpose of drug in a dose of 40 mg is contraindicated to patients with factors which can indicate predisposition to development of a myopathy (see the section "Contraindications"). At purpose of doses of 10 and 20 mg the recommended initial dose for this group of patients makes 5 mg (See the section "Contraindications").

Features of use:

Renal effects
At the patients receiving high doses of the drug Krestor® (generally 40 mg), the canalicular proteinuria which in most cases was tranzitorny was observed. Such proteinuria did not testify to an acute disease of kidneys or progressing of a disease of kidneys. At the patients accepting drug in a dose of 40 mg it is recommended to control indicators of function of kidneys during treatment.
From a musculoskeletal system
At use of the drug Krestor® in all dosages and, in particular at reception of the doses of drug exceeding 20 mg it was reported about the following impacts on a musculoskeletal system: mialgiya, myopathy, in rare instances рабдомиолиз.
Definition of a kreatinfosfokinaza
Definition of KFK should not be carried out after intensive exercise stresses or in the presence of other possible reasons of increase in KFK that can lead to incorrect interpretation of the received results. If the KFK initial level is significantly 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 KFK initial level (more than 5 times higher in comparison with the upper bound of norm).
Prior to therapy
At purpose of the drug Krestor®, also as well as at purpose of other inhibitors of GMG-KOA-reduktazy, patients should show care with the available risk factors of a myopathy / рабдомиолиза (see the section "With Care"), it is necessary to consider a ratio of risk and possible advantage of therapy and to make clinical observation.
During therapy
It is necessary to inform the patient on need of the immediate message to the doctor about cases of unexpected emergence of muscular pains, muscular weakness or spasms, especially in combination with an indisposition and fever. At such patients it is necessary to determine the KFK level. Therapy has to be stopped if the KFK level is considerably increased (more than by 5 times in comparison with the upper bound of norm) or if symptoms from muscles are sharply expressed and cause daily discomfort (even if the KFK level is 5 times less in comparison with the upper bound of norm). If symptoms disappear, and the KFK level is returned to norm, it is necessary to consider a question of repeated purpose of the drug Krestor® or other inhibitors of GMG-KOA-reduktazy in smaller doses at careful observation of the patient.
Routine control of KFK in the absence of symptoms is inexpedient.
Very exceptional cases of the immuno-mediated necrotizing myopathy with clinical manifestations in the form of resistant weakness of proximal muscles and increase in the KFK level in blood serum are celebrated during treatment or at the termination of reception of statines, including a rozuvastatina. Carrying out additional researches of a muscular and nervous system, serological researches, and also therapy by immunodepressive means can be required.
Signs of increase in impact on skeletal muscles at administration of drug of Krestor® and the accompanying therapy are noted. However it was reported about increase in number of cases of a miositis and myopathy at the patients accepting other inhibitors of GMG-KOA-reduktazy 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 inhibitors of GMG-KOA-reduktazy. Thus, co-administration of the drug Krestor® and a gemfibrozil is not recommended. The ratio of risk and possible advantage at combined use of the drug Krestor® and fibrat or lipidsnizhayushchy doses of niacin has to be carefully weighed. Administration of drug of Krestor® in a dose of 40 mg together with fibrata is contraindicated. (see the sections "Interaction with Other Medicines and Other Forms of Medicinal Interaction", "Contraindications").
In 2-4 weeks after an initiation of treatment and/or at increase in a dose of the drug Krestor® control of indicators of lipidic exchange is necessary (if necessary dose adjustment is required).
Liver
It is recommended to carry out definition of indicators of function of a liver prior to therapy and in 3 months after the beginning of therapy. Administration of drug of Krestor® it is necessary to stop or reduce a drug dose if the level of activity of transaminases in blood serum by 3 times exceeds the upper bound of norm.
At patients with a hypercholesterolemia owing to a hypothyroidism or a nephrotic syndrome therapy of basic diseases has to be carried out prior to treatment by the drug Krestor®.
Special populations. Ethnic groups
During the pharmacokinetic researches among the Chinese and Japanese patients increase in system concentration of a rozuvastatin in comparison with the indicators received among patients - Europeans is noted (see the sections "Route of Administration and Doses" and "Pharmacokinetics").
Inhibitors of proteases
Combined use of drug with inhibitors of proteases is not recommended (see the section "Interaction with Other Medicines and Other Types of Interaction").
Lactose
Drug should not be used at patients with a lactose intolerance, intolerance of a galactose and glyukozo-galaktozny malabsorption.
Intersticial disease of lungs
At use of some statines, especially for a long time, it was reported about isolated cases of an intersticial disease of lungs. Short wind, unproductive cough and deterioration in overall health (weakness, weight reduction and fever) can be displays of a disease. At suspicion of an intersticial disease of lungs it is necessary to stop therapy by statines.
Diabetes mellitus of the 2nd type
At patients with concentration of glucose from 5,6 to 6,9 mmol/l therapy by the drug Krestor® was associated with the increased risk of development of a diabetes mellitus of the 2nd type.
INFLUENCE ON ABILITY TO DRIVE THE CAR AND OTHER MECHANISMS
Researches on studying of influence of the drug Krestor® on ability to manage the vehicle and to use mechanisms were not conducted. However, based on pharmakodinamichesky properties, Krestor® should not make such impact. It is necessary to be careful at control of motor transport or the work connected with the increased concentration of attention and psychomotor reaction (during therapy there can be dizziness).

Side effects:

The side effects observed at administration of drug of Krestor® are usually expressed slightly and pass independently. As well as at use of other inhibitors of GMG-KOA-reduktazy, the frequency of emergence of side effects carries, generally dozozavisimy character.
Frequency of emergence of undesirable effects is presented as follows:
Often (> 1/100, <1/10); Infrequently (> 1/1000, <1/100); Seldom (> 1/10 000, <1/1 000); Very seldom (<1/10 000), including separate messages.
Immune system
Seldom: hypersensitivity reactions, including a Quincke's disease
Endocrine system
Often: diabetes mellitus of the 2nd type
From the central nervous system
Often: headache, dizziness
From a digestive tract
Often: lock, nausea, abdominal pains
Seldom: pancreatitis
From integuments
Infrequently: skin itch, rash, small tortoiseshell
From a musculoskeletal system
Often: mialgiya
Seldom: a myopathy (including a miositis), рабдомиолиз
Others
Often: asthenic syndrome
From an urinary system
At the patients receiving Krestor® the proteinuria can come to light. Changes of amount of protein in urine (from absence or trace quantities to ++ or more) are observed at less than 1% of the patients receiving 10 - 20 mg of drug and at about 3% of the patients receiving 40 mg of drug. Minor change of amount of protein in urine was noted at reception of a dose 20 mg. In most cases the proteinuria decreases or disappears in the course of therapy and does not mean emergence acute or progressing of the existing disease of kidneys.
From a musculoskeletal system
At use of the drug Krestor® in all dosages and, in particular at reception of the doses of drug exceeding 20 mg it was reported about the following impacts on a musculoskeletal system: a mialgiya, a myopathy (including a miositis), in rare instances – рабдомиолиз with an acute renal failure or without it.
Dozozavisimy increase in level of a kreatinfosfokinaza (KFK) is observed at insignificant number of the patients accepting розувастатин. In most cases it was insignificant, asymptomatic and temporary. In case of increase in the KFK level (more than by 5 times in comparison with the upper bound of norm) therapy has to be suspended (see the section "Special Instructions").
From a liver
At use of a rozuvastatin dozozavisimy increase in activity of "hepatic" transaminases at insignificant number of patients is observed. In most cases it is insignificant, asymptomatically and temporarily.
Laboratory indicators
At drug Krestor® use the following changes of laboratory indicators were also observed: increase in concentration of glucose, bilirubin, activity gamma глютамилтранспептидазы, alkaline phosphatase, dysfunction of a thyroid gland.
Post-marketing use
It was reported about the following side effects in post-marketing use of the drug Krestor®:
From a digestive tract
Very seldom: jaundice, hepatitis
Seldom: increase in activity of "hepatic" transaminases
Not specified frequency: diarrhea
From a musculoskeletal system
Very seldom: arthralgia
Not specified frequency: the immuno-mediated necrotizing myopathy
From the central nervous system
Very seldom: polyneuropathy, memory loss
From respiratory system
Not specified frequency: cough, short wind
From an urinary system
Very seldom: hamaturia
From integuments and a hypodermic fatty tissue
Not specified frequency: Stephens-Johnson's syndrome
From reproductive system and a mammary gland
Not specified frequency: gynecomastia
Others
Not specified frequency: peripheral hypostases
At use of some statines it was reported about the following side effects:
depression, sleep disorders, including sleeplessness and dreadful dreams, sexual dysfunction. It was reported about isolated cases of an intersticial disease of lungs, especially at prolonged use of drugs (see the section "Special Instructions").

Interaction with other medicines:

Cyclosporine: at simultaneous use of a rozuvastatin and AUC cyclosporine of a rozuvastatin was on average 7 times higher than value which was noted at healthy volunteers (see the section "Contraindications"). Combined use leads to increase in concentration of a rozuvastatin in a blood plasma by 11 times. Does not influence plasma concentration of cyclosporine.
Antagonists of vitamin K: the beginning of therapy rozuvastatiny or increase in a dose of drug at the patients receiving at the same time antagonists of vitamin K
(for example, warfarin), can lead to increase in a prothrombin time (the International Normalized Relation - MNO). Cancellation of a rozuvastatin or a dose decline of drug can lead to reduction of MNO. In such cases control of MNO is recommended.
Gemfibrozil and other hypolipidemic means: combined use of a rozuvastatin and gemfibrozil leads to increase twice in the maximum concentration of a rozuvastatin in a blood plasma and AUC of a rozuvastatin (see the section "Special Instructions"). Based on data on specific interaction, significant interaction from fenofibrata, perhaps pharmakodinamichesky interaction is not expected pharmacokinetically.
Gemfibrozil, фенофибрат, other fibrata and lipidsnizhayushchy doses of niacin increased risk of emergence of a myopathy at simultaneous use with GMG-KOA-reduktazy inhibitors, it is possible because they can cause a myopathy and when using as monotherapy (see the section "Special Instructions"). At a concomitant use of drug with gemfibrozily, fibrata, niacin in a dose more than 1 g/days are recommended to patients an initial dose of drug of 5 mg.
Эзетимиб: simultaneous use of the drug Krestor® and an ezetimib was not followed by change of AUC and Cmax of both medicines.
Inhibitors of proteases: in spite of the fact that the exact mechanism of interaction is unknown, joint reception of inhibitors of proteases can lead to significant increase in exposure of a rozuvastatin. The pharmacokinetic research on simultaneous use of 20 mg of a rozuvastatin with the combined drug containing two inhibitors of proteases (400 mg lopinavira/100 mg of a ritonavir) at healthy volunteers led to approximately double and fivefold increase in AUC (0-24) and Cmax of a rozuvastatin, respectively. Therefore the concomitant use of a rozuvastatin and inhibitors of proteases at treatment of patients with the human immunodeficiency virus (HIV) is not recommended (see the section "Special Instructions").
Antacids: simultaneous use of a rozuvastatin and suspensions of the antacids containing aluminum and magnesium hydroxide leads to decrease in plasma concentration of a rozuvastatin approximately for 50%. This effect is expressed more weakly if antacids are applied in 2 hours after reception of a rozuvastatin. Clinical value of similar interaction was not studied.
Erythromycin: simultaneous use of a rozuvastatin and erythromycin leads to AUC reduction (0 – t) a rozuvastatin for 20% and Cmax of a rozuvastatin for 30%. Similar interaction can result from strengthening of motility of the intestines caused by erythromycin reception.
Peroral contraceptives / гормонозаместительная therapy: simultaneous use of a rozuvastatin and oral contraceptives increases AUC ethinylestradiol and AUC of Norgestrelum by 26% and 34%, respectively. Such increase in plasma concentration has to be considered at selection of a dose of oral contraceptives. Pharmacokinetic data on simultaneous use of the drug Krestor® and gormonozamestitelny therapy are absent, therefore, it is impossible to exclude similar effect and at use of this combination. However the similar combination was widely used during conduct of clinical trials and well transferred by patients.
Other medicines: clinically significant interaction of a rozuvastatin with digoxin is not expected.
P450 cytochrome isoenzymes: results of the researches in vivo and in vitro showed what розувастатин is not either inhibitor, or the inductor
P450 cytochrome isoenzymes. Besides, розувастатин is weak substrate for these enzymes. Clinically significant interaction between rozuvastatiny and flukonazoly (inhibitor of isoenzymes of CYP2C9 and CYP3A4) and ketokonazoly was not noted (inhibitor of isoenzymes CYP2A6 CYP3A4). Combined use of a rozuvastatin and itrakonazol (CYP3A4 isoenzyme inhibitor) increases AUC of a rozuvastatin by 28% (clinically not significantly). Thus, the interaction connected with metabolism by P450 cytochrome is not expected.

Contraindications:

For tablets of 10 mg and 20 mg:
hypersensitivity to a rozuvastatin or any of drug components
liver diseases in an active phase, including permanent increase in serumal activity of transaminases and any increase in activity of transaminases in blood serum (more than by 3 times in comparison with the upper bound of norm)
the expressed renal failures (KK less than 30 ml/min.)
myopathy
concomitant use of cyclosporine
at women: pregnancy, the lactation period, lack of adequate methods of contraception to the patients predisposed to development of miotoksichesky complications a lactose intolerance, deficit of lactase or glyukozo-galaktozny malabsorption (drug contains lactose)
For tablets of 40 mg:
hypersensitivity to a rozuvastatin or any of drug components a concomitant use of cyclosporine
at women: pregnancy, lactation period, lack of adequate methods of contraception
liver diseases in an active phase, including permanent increase in serumal activity of transaminases and any increase in activity of transaminases in blood serum (more than by 3 times in comparison with the upper bound of norm) to patients with risk factors of development of a myopathy / рабдомиолиза, namely:
renal failure of moderate severity (KK less than 60 ml/min.)
hypothyroidism
the personal or family anamnesis of muscular diseases a miotoksichnost against the background of reception of other inhibitors of GMG-KOA-reduktazy or fibrat in the anamnesis excessive alcohol intake of a state which can lead to increase in plasma concentration of a rozuvastatin a concomitant use of fibrat to patients of Asian race a lactose intolerance deficit of lactase or glyukozo-galaktozny malabsorption (drug contains lactose)

WITH CARE
For tablets of 10 mg and 20 mg:
Existence of risk of development of a myopathy / рабдомиолиза - a renal failure, a hypothyroidism, the personal or family anamnesis of hereditary muscular diseases and the previous anamnesis of muscular toxicity when using other inhibitors of GMG-KOA-reduktazy or fibrat; excessive alcohol intake; the age is more senior than 65 years; states at which increase in plasma concentration of a rozuvastatin is noted; race (Asian race); co-administration from fibrata (see the section "Pharmacokinetics"); liver diseases in the anamnesis; sepsis; arterial hypotension; extensive surgical interventions, injuries, heavy metabolic, endocrine or electrolytic disturbances or uncontrollable convulsive attacks.
For tablets of 40 mg:
Renal failure of weak severity (KK more than 60 ml/min.); the age is more senior than 65 years; liver diseases in the anamnesis; sepsis; arterial hypotension; extensive surgical interventions, injuries, heavy metabolic, endocrine or electrolytic disturbances or uncontrollable convulsive attacks.
Use in pediatric practice
Efficiency and safety of use of drug for children up to 18 years is not established. Experience of use of drug in pediatric practice is limited by a small amount of children (of 8 years and is more senior) a family homozygous hypercholesterolemia. Now it is not recommended to apply Krestor® at children up to 18 years.
Patients with a liver failure Data or experience of use of drug for patients with point higher than 9 on a scale of Chayld-Pyyu is absent (see the sections "Pharmacodynamics" and "Special Instructions").
PREGNANCY AND PERIOD OF THE LACTATION
Крестор® it is contraindicated at pregnancy and in the period of a lactation.
Women of reproductive age have to apply adequate methods of contraception.
As cholesterol and other products of biosynthesis of cholesterol are important for fetation, the potential risk of inhibition of HMG-CoA reductase exceeds advantage of use of drug for pregnant women.
In case of pregnancy in the course of therapy administration of drug has to be stopped immediately.
Data concerning allocation of a rozuvastatin with breast milk are absent therefore during chest feeding administration of drug needs to be stopped (see the section "Contraindications").

Overdose:

At a concomitant use of several daily doses pharmacokinetic parameters of a rozuvastatin do not change.
Specific treatment at overdose rozuvastatiny does not exist. At overdose it is recommended to hold the symptomatic treatment and events directed to maintenance of functions of vitals and systems. Control of function of a liver and the KFK level is necessary. It is improbable that the hemodialysis will be effective.

Storage conditions:

At a temperature not above 30 °C, in the place, unavailable to children. Period of validity 3 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, on 10 mg, 20 mg and 40 mg.
For tablets of 10 mg: on 7 tablets in the blister from an aluminum laminate / aluminum foil created from the forming laminate consisting of polyamide / a soft aluminum foil / an unplasticized polyvinyl chloride (PVC) film, sealed by the tempered aluminum foil covered with a thermovarnish; on 1 blister in a cardboard pack with the application instruction,
or on 14 tablets in the blister from an aluminum laminate / aluminum foil created from the forming laminate consisting of polyamide / a soft aluminum foil / an unplasticized polyvinyl chloride (PVC) film, sealed by the tempered aluminum foil covered with a thermovarnish; on 2 or 7 blisters in a cardboard pack with the application instruction.
For tablets of 20 mg: on 14 tablets in the blister from an aluminum laminate / aluminum foil created from the forming laminate consisting of polyamide / a soft aluminum foil / an unplasticized polyvinyl chloride (PVC) film, sealed by the tempered aluminum foil covered with a thermovarnish; on 2 blisters in a cardboard pack with the application instruction.
For tablets of 40 mg: on 7 tablets in the blister from an aluminum laminate / aluminum foil created from the forming laminate consisting of polyamide / a soft aluminum foil / an unplasticized polyvinyl chloride (PVC) film, sealed by the tempered aluminum foil covered with a thermovarnish; on 4 blisters in a cardboard pack with the application instruction.