Роксера®

General characteristics. Structure:

Active ingredient: 5 mg, 10 mg, 15 mg or 20 mg of a rozuvastatin.

Vspomogatelna of substance: Cellulose microcrystallic, Lactose, Silicon dioxide colloid, Magnesium stearate.

Cover. Butylmethacrylate, dimethylaminoethylmethacrylate and methylmethacrylate copolymer [1:2:1], Makrogol - 6000, Titanium dioxide, Lactoses monohydrate.

Drug, corrective lipidic exchange, reducing cholesterol level.

Pharmacological properties:

Pharmacodynamics. The drug Roksera® - hypolipidemic means. Active ingredient of drug - розувастатин, is the selection, competitive inhibitor of HMG-CoA reductase, the enzyme turning 3-hydroxy-3-metilglutarilkoferment A into mevalonovy acid - the predecessor of cholesterol. The main target of action of a rozuvastatin is the liver where there is a synthesis of cholesterol (XC) and a catabolism of lipoproteins of the low density (LPNP). Increases number of hepatic receptors to 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.

Rozuvastatin reduces the increased plasma concentration of LPNP (HS-LPNP) cholesterol, general cholesterol, triglycerides (TG), increases concentration of cholesterol of lipoproteins of the high density (HS-LPVP). It also reduces concentration of apolipoprotein B (Apov), HS-NELPVP, HS-LPONP, TG-LPONP also increases concentration of A-I apolipoprotein in a blood plasma. Rozuvastatin reduces a ratio of HS-LPNP/HS-LPVP, the general HS/HS-LPVP and HS-NELPVP/HS-LPVP and a ratio of Apov/Apoa-I.

The therapeutic effect develops within one week after the beginning of therapy, 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 further regular administration of drug.

Drug is effective at adult patients with a hypercholesterolemia with the accompanying gipertriglitseridemiya or without it, regardless of race, a floor or age, including at patients with a diabetes mellitus or a family hypercholesterolemia. Read detailed article with results of researches as far as розувастатин lowers risk of the first and repeated heart attack, cardiovascular diseases mortality.

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 reception of a rozuvastatin in a dose of 10 mg concentration of HS-LPNP reaches values less than a mmol/l.

At patients with a homozygous family hypercholesterolemia розувастатин it was applied in doses of 20-40 mg, average decrease made 22%. The additive effect is noted in a combination with fenofibraty concerning the maintenance of TG and with niacin in lipidsnizhayushchy doses concerning concentration of HS-LPVP.

Pharmacokinetics. The maximum concentration of a rozuvastatin in a blood plasma is reached approximately in 5 h after intake. Absolute bioavailability makes about 20%.

It is metabolized preferential by a liver which is the main body synthesizing cholesterol and metabolizing 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.

Is exposed to limited metabolism (about 10%). Rozuvastatin is nonspecific substrate of P450 cytochrome. The main isoenzyme participating in metabolism of a rozuvastatin is CYP2C9 isoenzyme. Isoenzymes of CYP2C19, CYP3A4, CYP2D6 are involved in metabolism to a lesser extent. The main revealed metabolites are N-desmetilrozuvastatin and lactonic metabolites.

N-desmetilrozuvastatin for about 50% is less active, than розувастатин, lactonic metabolites pharmacological are inactive. More than 90% of pharmacological activity on inhibition of plasma GMG-KOA-reduktazy are provided rozuvastatiny, the rest - its metabolites.

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 elimination half-life (T1/2) makes about 19 h of a blood plasma (does not change at increase in a dose of drug). Average geometrical plasma clearance - 50 l/h. As well as in case of other inhibitors of GMG-KOA-reduktazy, 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.

System exposure of a rozuvastatin increases in proportion to a dose. Pharmacokinetic parameters do not change at daily reception.

Gender and age do not exert clinically significant impact on pharmacokinetics of a rozuvastatin.

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 Mongoloids (Japanese, Chinese, Filipinos, Vietnamese and Koreans) in comparison with Caucasians; at Indians 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 Caucasians and Negroids.

At patients with the slight and moderately expressed renal failure the size of plasma concentration of a rozuvastatin or N-desmetilrozuvastatina significantly does not change. At patients with a heavy 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-desmetilrozuvastatina is 9 times higher, than at healthy volunteers. Concentration of a rozuvastatin in a blood plasma at the patients who are on a hemodialysis is about 50% higher, than at healthy volunteers.

At patients with a chronic alcoholic liver disease plasma concentration of a rozuvastatin moderately increases. In comparison with patients with normal function of a liver at patients with a liver failure (a class A on a scale of Chayld-Pyyu) Cmax and AUC of a rozuvastatin increases by 60 and 5%, respectively; at patients with a liver failure (a class B on a scale of Chayld-Pyyu), these indicators increase by 100 and 21%, respectively. Experience of use of a rozuvastatin for patients a liver failure (a class C on a scale of Chayld-Pyyu (more than 9 points)) is absent.

Indications to use:

• Primary hypercholesterolemia across Fredrikson (IIa type) or the mixed dislipidemiya (IIb type) as addition to a diet at inefficiency of a diet and other non-drug methods of treatment (for example, exercise stresses, decrease in body weight).
• A family homozygous hypercholesterolemia as addition to a diet and other hypolipidemic therapy (for example, LPNP-aferez) or if such therapy is not 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 plasma concentration of XC and HS-LPNP is shown.
• Primary prevention of the main cardiovascular complications (a stroke, a myocardial infarction, arterial revascularization) at adult patients without clinical signs of the coronary heart disease (CHD), 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 plasma concentration of S-reactive protein (≥2 g/l) in the presence are more senior, than at least one of accessory factors of risk, such as: arterial hypertension, low plasma concentration of HS-LPVP, smoking, the early beginning of an ischemic heart disease in the family anamnesis).

Route of administration and doses:

Due to the possible development of side effects at use of a dose of 40 mg/days, in comparison with lower doses of drug, increase in a dose to 40 mg/days after additional use 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 development of cardiovascular complications (especially at patients with a family hypercholesterolemia) at which the desirable result of therapy at use of a dose of 20 mg/days and which will be under observation of the doctor was not achieved. Especially careful observation of the patients receiving drug in a dose of 40 mg/days is recommended.

Use of a dose of 40 mg/days for the patients who were earlier not seeing a doctor is not recommended. After 2–4 weeks of therapy and/or at increase in a dose of the drug Roksera® control of indicators of lipidic exchange is necessary (if necessary dose adjustment is required).

With a renal failure easy or moderate severity of dose adjustment is not required from patients. At patients with a heavy renal failure (KK less than 30 ml/min.) use of the drug Roksera® is contraindicated. Use of drug in a dose more than 30 mg/days is contraindicated to patients with a renal failure of average and heavy degree (KK less than 60 ml/min.). To patients with a renal failure of average degree the recommended initial dose of drug makes 5 mg/days.

The drug Roksera® is contraindicated to patients with liver diseases in an active phase.

Experience of use of drug for patients with a liver failure is higher than 9 points (class C) on a scale of Chayld-Pyyu, no.

To patients 65 years are aged more senior it is recommended to begin use of drug with a dose of 5 mg/days.

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. It is necessary to consider this fact at drug Roksera® use to these groups of patients. At use of doses of 10 and 20 mg/days the recommended initial dose for patients of Mongoloid race makes 5 mg/days. Use of drug in a dose of 40 mg is contraindicated to patients of Mongoloid race.

Use of drug in a dose of 40 mg to the patients predisposed to development of miotoksichesky complications contraindicated. In need of use of doses of 10 and 20 mg/days the recommended initial dose for this group of patients makes 5 mg.

At use with gemfibrazily the dose of the drug Roksera® should not exceed 10 mg/days.

Features of use:

The drug Roksera® is contraindicated at pregnancy and in the period of a lactation. Women of reproductive age have to apply adequate methods of contraception. As the cholesterol and substances synthesized from cholesterol are important for fetation, the potential risk of inhibition of GMG-KOA-reduktazy for a fruit exceeds advantage of use of drug at pregnancy. In case of approach of pregnancy in the course of therapy use of drug has to be immediately stopped. Data concerning allocation of a rozuvastatin with breast milk are absent (it is known that other inhibitors of GMG-KOA-reduktazy capable to be allocated with breast milk) therefore during feeding by a breast use of drug needs to be stopped.

Renal failure. At the patients receiving high doses of a rozuvastatin (in particular 40 mg/days), the canalicular proteinuria which came to light by means of test strips was observed and in most cases was periodic or short-term. Such proteinuria does not testify about acute or progressing of an associated disease of kidneys. The frequency of serious violations of function of kidneys noted at post-marketing studying of a rozuvastatin is higher than 40 mg/days at reception of a dose. At the patients accepting the drug Roksera® in a dose of 30 or 40 mg/days it is recommended to control indicators of function of kidneys during treatment (at least 1 time in 3 months).

Influence on a musculoskeletal system. At use of a rozuvastatin in all doses, but in particular in the doses exceeding 20 mg/days it was reported about the following impacts on a musculoskeletal system: mialgiya, myopathy, in rare instances рабдомиолиз. Very exceptional cases of a rabdomioliz at simultaneous use of inhibitors of GMG-KOA-reduktazy and an ezetimib are celebrated. Such combination has to be applied with care as it is impossible to exclude pharmakodinamichesky interaction.

As well as in case of other inhibitors of GMG-KOA-reduktazy, the frequency of a rabdomioliz at post-marketing use of the drug Roksera® is higher than 40 mg/days at use of a dose.

Definition of activity of KFK. Activity of KFK cannot be defined after intensive exercise stresses and in the presence of other possible reasons of increase in its activity; it can lead to incorrect interpretation of the received results. If initial activity of KFK is significantly exceeded (5 times higher than the upper bound of norm), in 5–7 days it is necessary to carry out retest. It is impossible to begin therapy if results of retest confirm initial high activity of KFK (more than 5-fold exceeding of the upper bound of norm).

Before therapy. Depending on a daily dose the drug Roksera® has to be appointed with care to patients with the available risk factors of a myopathy / рабдомиолиза or use of drug is contraindicated (see sections of "Contraindication" and "With Care"). Treat such factors:
- renal failure;
- hypothyroidism;
- diseases of muscles in the anamnesis (including in family);
- the miotoksichesky phenomena at reception of other inhibitors of GMG-KOA-reduktazy or fibrat in the anamnesis;
- excessive alcohol intake;
- the age is more senior than 65 years;
- states at which concentration of a rozuvastatin in a blood plasma can increase;
- simultaneous use of fibrat.

At such patients it is necessary to estimate risk and possible advantage of therapy. Also it is recommended to carry out clinical monitoring. If initial activity of KFK is more than 5 times higher in comparison with the upper bound of norm, therapy by the drug Roksera® cannot be begun.

During therapy by drug. It is necessary to inform the patient on need of the immediate message to the doctor in case 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 define activity of KFK. Therapy has to be stopped if activity of KFK 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 activity of KFK no more than by 5 times exceeds the upper bound of norm). If symptoms disappear and activity of KFK is returned to norm, it is necessary to consider a question of resuming of use of the drug Roksera® or other inhibitors of GMG-KOA-reduktazy in smaller doses at careful medical observation. Control of activity of KFK in the absence of symptoms is inexpedient.

Signs of increase in impact on skeletal muscles at reception of a rozuvastatin 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 fibroyevy acid (for example, gemfibrozit), cyclosporine, niacin in lipidsnizhayushchy doses (more than 1 g/days), antifungal means - derivatives of an azol, inhibitors of HIV protease and makrolidny antibiotics.

At simultaneous use with some inhibitors of GMG-KOA-reduktazy gemfibrozit increases risk of development of a myopathy. Thus, simultaneous use of the drug Roksera® and a gemfibrozil is not recommended (in doses less than 30 mg/days). Advantages of further change of plasma concentration of lipids at the combined use of the drug Roksera® with fibrata or niacin in lipidsnizhayushchy doses have to be carefully weighed taking into account possible risk. Rozuvastatin in a dose of 30 mg/days is also more contraindicated for a combination therapy from fibrata.

Due to the increase in risk of a rabdomioliz the drug Roksera® should not be used to patients with acute states to which can lead to the myopathy or states contributing to development of a renal failure (for example, sepsis, arterial hypotension, extensive surgical interventions, injuries, heavy metabolic, endocrine and electrolytic disturbances or uncontrollable spasms).

Liver. Depending on a daily dose the drug Roksera® has to be used with care at patients with excessive alcohol intake and/or having in the anamnesis of a disease of a liver or its use is contraindicated (see sections of "Contraindication" and "With Care").
It is recommended to carry out definition of functional trials of a liver prior to therapy and in 3 months after its beginning. Use of the drug Roksera® it is necessary to stop or reduce a drug dose if activity of "hepatic" 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 prior to treatment by the drug Roksera® therapy of basic diseases has to be carried out.

Ethnic features. During the pharmacokinetic researches at Mongoloids in comparison with Caucasians increase in plasma concentration of a rozuvastatin is noted.

The drug Roksera® contains lactose in this connection it should not be applied to patients with a lactose intolerance, deficit of lactase, a syndrome of glyukozo-galaktozny malabsorption.

Influence on ability to manage motor transport and other technical devices: researches on studying of influence of the drug Roksera® on ability to manage vehicles and work with mechanisms were not conducted. Nevertheless, considering a possibility of development of dizziness, etc. side effects, it is necessary to be careful at control of the vehicles and other mechanisms demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Classification of frequency of development of side effects:
very often     > 1/10
often                   > 1/100, but <1/10
infrequently              > 1/1000, but <1/100
seldom                 > 1/10000, but <1/1000
very seldom    <1/10000, including separate messages.
Frequency of emergence of side effects depends on the accepted dose.
From immune system seldom: hypersensitivity reactions, including a Quincke's disease;

From the central nervous system often: headache, dizziness; very seldom: polyneuropathy, memory loss;

From the alimentary system often: lock, nausea, abdominal pain;
seldom: pancreatitis, increase in activity of "hepatic" transaminases; very seldom: jaundice, hepatitis, diarrhea;

From integuments infrequently: skin itch, rash, small tortoiseshell; very seldom: Stephens-Johnson's syndrome;

From a musculoskeletal system and connecting fabric it is frequent: mialgiya; seldom: a myopathy (including a miositis) and рабдомиолиз; very seldom: arthralgia.

Dozozavisimy increase in activity of a kreatinfosfokinaza (KFK) is observed at a small number of the patients accepting розувастатин. In most cases it is insignificant, asymptomatic and temporary. In case of increase in activity of KFK therapy more than 5 times higher than the upper bound of norm should be suspended.

From an urinary system a chasto:proteinuriya (less than 1% of the patients receiving a dose of 10-20 mg/days and about 3% of the patients receiving a dose of 40 mg/days). In most cases the proteinuria decreases or disappears in the course of therapy and does not mean developing of the acute or progressing associated disease of kidneys; very seldom: hamaturia.

General disturbances often: adynamy.

Laboratory indicators. Increase in activity of KFK, concentration of glucose, bilirubin, activity gamma глутамилтранспептидазы, alkaline phosphatase, change of plasma concentration of hormones of a thyroid gland.

Interaction with other medicines:

Cyclosporine. At simultaneous use of a rozuvastatin and cyclosporine, AUC of a rozuvastatin is on average 7 times higher than value which is noted at healthy volunteers. Plasma concentration of a rozuvastatin increases by 11 times.

Simultaneous use with rozuvastatiny does not influence concentration of cyclosporine in a blood plasma.

Indirect anticoagulants. As well as in case of other inhibitors of HMG-CoA reductase, the beginning of therapy rozuvastatiny or increase in its dose at the patients accepting at the same time indirect anticoagulants (for example, warfarin), can lead to increase in the International normalized relation (MHO). Cancellation of a rozuvastatin or decrease in its dose can lead to MHO reduction. In such cases MHO monitoring is recommended.

Эзетимиб. Simultaneous use of a rozuvastatin and ezetimib is not followed by change of AUC or Cmax of both drugs. However it is impossible to exclude pharmakodinamichesky interaction between rozuvastatiny and ezetimiby, shown increase in risk of development of undesirable reactions from muscles.

Gemfibrozil and other hypolipidemic means. Simultaneous use of a rozuvastatin and gemfibrozil leads to increase in Cmax and AUC of a rozuvastatin twice. Gemfibrozil, фенофибрат, other fibrata and lipidsnizhayushchy doses of niacin (a dose big or equivalent 1 g/days) increased risk of emergence of a myopathy at simultaneous use with GMG-KOA-reduktazy inhibitors (perhaps because they can cause a myopathy and at use in monotherapy). Simultaneous use of fibrat and a rozuvastatin in a daily dose of 30 mg is contraindicated. At such patients therapy has to begin with a dose of 5 mg/days.

HIV protease inhibitors. Simultaneous use of inhibitors of HIV protease can increase plasma concentration of a rozuvastatin considerably. Simultaneous use of 20 mg of a rozuvastatin and combination of two inhibitors of HIV protease (400 mg of a lopinavir / 100 mg of a ritonavir) is followed by increase in equilibrium AUC(0-24 of the h) and Cmax of a rozuvastatin in 2 and 5 times, respectively.

Antacids. Simultaneous use of a rozuvastatin and antacids, the 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 h after reception of a rozuvastatin.

Erythromycin. Simultaneous use of a rozuvastatin and erythromycin leads to reduction of AUC(0-t) of a rozuvastatin by 20% and its Cmax by 30%. Similar interaction can result from strengthening of motility of the intestines caused by erythromycin use.

Hormonal contraceptives / replacement hormonal therapy (RHT). Simultaneous use of a rozuvastatin and hormonal contraceptives increases AUC ethinylestradiol and Norgestrelum by 26% and 34%, respectively. Such increase in concentration in a blood plasma has to be considered at selection of a dose of hormonal contraceptives.

Pharmacokinetic data on simultaneous use of a rozuvastatin and replacement hormonal therapy are absent, therefore, it is impossible to exclude similar effect and at use of this combination. However the similar combination was widely applied 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. Rozuvastatin is not either inhibitor, or the P450 cytochrome inductor. Besides, розувастатин is weak substrate for this system of isoenzymes.

Clinically significant interaction between rozuvastatiny and flukonazoly (inhibitor of isoenzymes of CYP2C9 and CYP3A4) and ketokonazoly (inhibitor of isoenzymes of CYP2A6 and CYP3A4) is noted. Simultaneous use of a rozuvastatin and itrakonazol (CYP3A4 isoenzyme inhibitor) increases AUC of a rozuvastatin by 28% that clinically not significantly. Thus, the interaction connected with P450 cytochrome is not expected.

Contraindications:

Inside not to chew and not to crush, swallow a tablet entirely, washing down with water, reception irrespective of meal is possible at any time.

Prior to therapy by the drug Roksera® 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 national recommendations about target concentration of lipids in a blood plasma.

The recommended initial dose for the patients beginning to accept drug or for the patients transferred from reception of other inhibitors of GMG-KOA-reduktazy has to make 5 or 10 mg of the drug Роксера® 1 of times a day.

At simultaneous 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.

At the choice of an initial dose it is necessary to be guided by individual concentration of cholesterol in a blood plasma and to take possible risk of development of cardiovascular complications into account; it is also necessary to consider potential risk of development of side effects. In case of need, the dose can be increased in 4 weeks.

At a daily dose to 30 mg
- Hypersensitivity to a rozuvastatin or any of drug components;
- liver diseases in an active phase (including permanent increase in activity of "hepatic" transaminases and increase in activity of "hepatic" transaminases in blood serum more than by 3 times in comparison with the upper bound of norm);
- heavy renal failure (KK less than 30 ml/min.);
- myopathy;
- concomitant use of cyclosporine;
- the patients predisposed to development of miotoksichesky complications;
- pregnancy, breastfeeding period;
- use for the women of childbearing age who are not using adequate methods of contraception;
- lactose intolerance, deficit of lactase, syndrome of glyukozo-galaktozny malabsorption;
- age up to 18 years.

At a daily dose of 30 mg and more
- Hypersensitivity to a rozuvastatin or any of drug components;
- liver diseases in an active phase (including permanent increase in activity of "hepatic" transaminases and increase in activity of "hepatic" transaminases in blood serum more than by 3 times in comparison with the upper bound of norm);
- renal failure of average and heavy degree (KK less than 60 ml/min.);
- myopathy;
- simultaneous use of cyclosporine;
- the patients predisposed to development of miotoksichesky complications;
- pregnancy, breastfeeding period;
- use for the women of childbearing age who are not using adequate methods of contraception;
- hypothyroidism;
- diseases of muscles in the anamnesis (including in family);
- a miotoksichnost at use of other inhibitors of GMG-KOA-reduktazy or fibrat in the anamnesis;
- excessive alcohol intake;
- states which can lead to increase in concentration of a rozuvastatin in a blood plasma;
- simultaneous use of fibrat;
- lactose intolerance, deficit of lactase, syndrome of glyukozo-galaktozny malabsorption;
- patients of Mongoloid race;
- age up to 18 years.

With care.
At a daily dose to 30 mg
Existence of risk of development of a myopathy / рабдомиолиза - a renal failure, a hypothyroidism, hereditary diseases of muscles in the anamnesis (including in family) and the previous anamnesis of muscular toxicity at use of 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 (Mongoloid race - Japanese and Chinese); simultaneous use from fibrata; liver diseases in the anamnesis; sepsis; arterial hypotension; extensive surgical interventions, injuries, heavy metabolic, endocrine or electrolytic disturbances or uncontrollable spasms, simultaneous use with ezetimiby.

At a daily dose of 30 mg and more
Renal failure of easy 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 spasms, simultaneous use with ezetimiby.

Overdose:

The clinical picture of overdose is not described. At one-time reception of several daily doses of drug pharmacokinetic parameters of a rozuvastatin do not change. Overdose treatment — symptomatic, control of function of a liver and activity of KFK is necessary; the specific antidote does not exist, the hemodialysis is inefficient.

Storage conditions:

At a temperature not above 30 °C. To store in the place, unavailable to children. List B

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 5 mg, 10 mg, 15 mg and 20 mg. On 10 tablets in the blister. On 3 blisters in a cardboard pack together with the application instruction