Mertenil

General characteristics. Structure:

Active agent: розувастатин calcium of 5,2 mg it is equivalent to a rozuvastatin of 5 mg, розувастатин calcium of 10,4 mg it is equivalent to a rozuvastatin of 10 mg, розувастатин calcium of 20,8 mg it is equivalent to a rozuvastatin of 20 mg, розувастатин calcium of 41,6 mg it is equivalent to a rozuvastatin of 40 mg.

Excipients: cellulose microcrystallic 12, lactoses monohydrate, magnesium hydroxide, кросповидон (Type A), magnesium stearate;
structure of a film cover: Опадрай the II white (talc, macrogoal-3350, titanium E171 dioxide, polyvinyl alcohol).

Pharmacological properties:

Pharmacodynamics. Rozuvastatin represents the selection and competitive inhibitor of HMG-CoA reductase, the enzyme turning Z-gidroksi-Z-metilglyutarilkoenzim And in мевалонат which is a 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.
It also slows down synthesis of cholesterol of lipoproteins of very low density (LPONP) in liver cells, thereby reducing the general maintenance of LPNP and LPONP. Rozuvastatin reduces the increased content of cholesterol - LPNP (HS-LPNP), the general cholesterol and triglycerides (TG), increases the content of cholesterol of lipoproteins of the high density (HS-LPVP), and also reduces the content of apolipoprotein B (Apov), HS-NELPVP (content of the general cholesterol minus the content of LPVP, HS-LPONP, TG-LPONP cholesterol and increases the level of A-I apolipoprotein (Apoa-1). Rozuvastatin reduces a ratio of HS-LPNP/HS-LPVP, the general HS/HS-LPVP, HS-NELPVP/HS-LPVP and Apov/Apoa-1.
The therapeutic effect can be reached within one week after an initiation of treatment, in 2 weeks 90% of the greatest possible effect are reached. Usually greatest possible therapeutic effect is reached in 4 weeks and supported at further administration of drug.

Clinical performance. Rozuvastatin is effective at treatment of adult patients with a hypercholesterolemia with or without gipertriglitseridemiya symptoms, regardless of their race, a floor or age, and also at treatment of special category of the patients sick with a diabetes mellitus or a hereditary form of a family hypercholesterolemia. Rozuvastatin is effective for treatment of patients with a hypercholesterolemia like IIA and IIb across Frederikson (the average HS-LPNP initial level about 4,8 mmol/l). At 80% of the patients receiving 10 mg of a rozuvastatin the target values of the HS-LPNP level established by the European society on an atherosclerosis research (less than 3 mmol/l) were reached.
At the patients with a heterozygous family hypercholesterolemia accepting розувастатин in doses from 20 to 80 mg according to the scheme of the forced titration of doses all the accepted doses had significant effect on change of the parameters characterizing the maintenance of lipids and on achievement of the goal of therapy. As a result of titration of doses to 40 mg a day (12 weeks of therapy) the maintenance of HS-LPNP decreased by 53%. At 33% of patients HS-LPNP values (lower than 3 mmol/l) meeting target standards of the guide of the European society on an atherosclerosis research were reached.
At the patients with a homozygous family hypercholesterolemia accepting розувастатин in doses of 20 and 40 mg, average decrease in maintenance of HS-LPNP made 22%. The additive effect is noted in a combination with fenofibraty concerning the maintenance of TG and with niacin (more than 1 g a day) concerning the maintenance of HS-LPVP. Researches on influence of a rozuvastatin on decrease in quantity of the complications caused by lipidic disturbances, such as an ischemic disease are not completed yet.
Patients with low risk level have diseases of coronary heart disease (certain how risk across Framingem less than 10% during more than 10 years), with average value of maintenance of HS-LPNP of 4,0 mmol/l (154,5 mg/dl) розувастатин in a dose of 40 mg/days considerably slowed down increase in the maximum size characterizing a thickening of a wall of a carotid artery in 12 segments in comparison with placebo with a speed of-0,0145 mm/year (95% a confidence interval (CI): from-0,0196 to - 0,0093, at р <0,0001). Patients should appoint a dose of 40 mg only with a severe form of a hypercholesterolemia and a high risk of development of cardiovascular diseases.

Pharmacokinetics. Absorption: the maximum concentration of a rozuvastatin in a blood plasma is reached in 5 h after intake of the corresponding dose. Absolute bioavailability makes about 20%.
Distribution: розувастатин it is absorbed preferential by a liver which is the main place of synthesis of cholesterol and clearance of metabolism of HS-LPNP. The volume of distribution of a rozuvastatin makes about 134 l. 90% of a rozuvastatin contact proteins of a blood plasma, generally albumine.
Metabolism: is exposed to limited metabolism (about 10%). Rozuvastatin is rather non-core substrate for metabolism by enzymes of system of P450 cytochrome. CYP2C9 is the main isoenzyme participating in metabolism while isoenzymes of CYP2C19, CYP3A4 and CYP2D6 are involved in metabolism to a lesser extent. The main metabolite - N-desmetil which for 50% is less active, than розувастатин. Lactonic metabolites pharmacological are inactive. 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 the accepted dose of a rozuvastatin are removed in not changed view from an organism through intestines (including absorbed and not absorbed розувастатин), and the rest is removed in not changed look by kidneys. The elimination half-life (Тш) makes 19 h, does not change at increase in a dose of drug. The average geometrical plasma clearance makes about 50 l/h (coefficient of variation of 21,7%). As well as in a case with other inhibitors of HMG-CoA reductase, the membrane carrier of cholesterol through membranes - a transport protein From organic anions is involved in process of "hepatic" capture of a rozuvastatin. This carrier plays a large role in removal of a rozuvastatin liver.
Linearity: system exposure of a rozuvastatin increases in proportion to a dose. Changes of pharmacokinetic parameters at administration of drug several times in days are not noted.
Age and floor: gender and age do not exert clinically significant impact on pharmacokinetic parameters of a rozuvastatin.
Ethnic groups: comparative researches of pharmacokinetics showed double increase in average AUC value (the area under a curve "concentration - time") and TCmax (time of achievement of the maximum concentration of drug in a blood plasma) at patients of an Asian origin (Japanese, Chinese, Filipinos, Vietnamese and Koreans) in comparison with indicators at representatives of Caucasian race. At Indians exceeding approximately by 1,3 times of average AUC and Cmax-value at the same time was noted the analysis of indicators of pharmacokinetics for all studied population did not reveal clinically significant distinctions in drug pharmacokinetics among representatives of Caucasian, negroid races, Latin Americans.

Renal failure: patients with easy and moderate degree of a renal failure have a plasma concentration of a rozuvastatin or N-desmetil of a metabolite 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-desmetil of a metabolite is 9 times higher in comparison with healthy volunteers. Concentration of a rozuvastatin in a blood plasma at the patients who are on a hemodialysis was about 50% higher, than at healthy volunteers.
Liver failure: at patients with various degree of a liver failure with point 7 and below on a scale of Chayld-Pyyu increase Т½ in a rozuvastatin is not revealed. However at 2 patients with points 8 and 9 on a scale of Chayld-Pyyu lengthening Т½ approximately twice Chayld-Pyyu exceeding a similar indicator for patients with lower indicators on a scale was noted. Experience of use of a rozuvastatin for patients with point higher than 9 on a scale of Chayld-Pyyu is absent.

Indications to use:

- a hypercholesterolemia and the combined (mixed) dislipidemichesky states for decrease in the increased concentration of the general cholesterol, cholesterol of lipoproteins of low density, apolipoprotein B and triglycerides in blood serum as addition to a dietotherapy. Learn here what lowers "bad" cholesterol better: Mertenil or other drugs of a rozuvastatin.

- a family homozygous hypercholesterolemia as addition to a dietotherapy and other methods of lipidsnizhayushchy therapy (for example, LPNP-aferez) or in cases when such therapy is insufficiently effective.

Route of administration and doses:

Before an initiation of treatment the patient should keep to a standard diet using products with the low content of cholesterol which has to be continued also during the entire period of treatment. Doses of drug should be selected individually according to the purpose of the carried-out treatment and the therapeutic response of the patient to the carried-out therapy, considering the modern standard recommendations about the target objectives of lipids.
Inside, at any time, irrespective of meal not to chew and not to crush, swallow entirely, washing down with water.
The recommended initial dose of drug makes 5 mg or 10 mg of 1 times a day as for the patients who were earlier not accepting statines and for the patients transferred to reception of this drug after therapy by other inhibitors of HMG-CoA reductase. Choosing an initial dose of drug, it is necessary to consider cholesterol level at each specific patient, and also possible risk of development of cardiovascular complications and potential risk of emergence of side effects. In case of need in 4 weeks it is possible to carry out correction of a dose. 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"), final titration to the maximum dose of 40 mg should be carried out only at patients with a severe form of a hypercholesterolemia and high risk of emergence of cardiovascular complications (especially at patients with a hereditary hypercholesterolemia) at which at reception of a dose in 20 mg the target objective of cholesterol and which will be under medical observation was not reached. At purpose of a dose of 40 mg careful observation of the doctor is recommended. Purpose of a dose of 40 mg is not recommended to the patients who were earlier not seeing a doctor!

Elderly patients
For patients 70 years the recommended initial dose of drug are more senior makes 5 mg. Correction of a dose in connection with age is not required.
Patients with a renal failure
With a renal failure easy or moderate severity dose adjustment is not required from patients. The recommended initial dose of drug makes 5 mg for patients with a renal failure of moderate severity (KK less than 60 ml/min.). Purpose of Mertenila® in any doses is contraindicated to patients with heavy degree of a renal failure (see the section "Contraindications"). Purpose of drug in a dose of 40 mg is contraindicated to patients with a renal failure of moderate severity.
Patients with a liver failure
Increases in system concentration of a rozuvastatin at patients with point on a scale of Chaylda-Pyyu, equal 7 and below, it is not revealed. However increase in system concentration of drug was observed at patients with points on a scale of Chaylda-Pyyu 8 and 9. At such patients it is necessary to control function of a liver against the background of therapy. Data on administration of drug by patients with point on a scale of Chaylda-Pyyu higher than 9 are absent. To patients with liver diseases in the active phase Mertenil® it is contraindicated.

Ethnic groups. At patients of Asian race increase in system concentration of a rozuvastatin is possible. At purpose of doses of 10 and 20 mg the recommended initial dose of drug for patients of an Asian origin makes 5 mg. Use of drug in a dose of 40 mg is contraindicated to such patients (see the section "Contraindications").
The patients predisposed to a myopathy
At purpose of doses of 10 and 20 mg the recommended initial dose of drug for patients with predisposition to a myopathy makes 5 mg. Use of drug in a dose of 40 mg is contraindicated to such patients.

Features of use:

The proteinuria, preferential canalicular origin, was noted at patients at reception of high doses of Mertenila®, in particular 40 mg, but in most cases was periodic or short-term. It is shown that such proteinuria does not mean emergence acute or progressing of the existing disease of kidneys. Frequency of serious violations of function of kidneys increases at reception of 40 mg of a rozuvastatin. It is recommended to control indicators of function of kidneys during therapy by the drug Mertenil®.
At use of Mertenila® in all dosages, and in particular at administration of drug in the dose exceeding 20 mg the mialgiya, a myopathy and, in rare instances, рабдомиолиз came to light. Very seldom arose рабдомиолиз at a concomitant use of an ezetimib and inhibitors of GMG-KOA-reduktazy. In this case it is impossible to exclude pharmacological interaction of drugs therefore jointly Mertenil® and эзетимиб should be applied with care (see the section "Interaction with Other Medicines").
Frequency of cases of a rabdomioliz at reception of 40 mg of a rozuvastatin increases.
Definition of activity of KFK should not be carried out after the intensive exercise stresses causing increase in KFK as it can complicate interpretation of results. At increase in an indicator of KFK prior to therapy of norm more than 5 times higher than the upper bound in 5-7 days it is necessary to take repeated measurement. If repeated measurement confirms an initial indicator of KFK (5 times higher in comparison with the upper bound of norm) therapy of Mertenilom® should not be begun.
Мертенил®, as well as other inhibitors of GMG-KOA-reduktazy, patients should appoint with extra care with the available risk factors of a myopathy / рабдомиолиза. Treat such factors:

- renal failure;
- a hypothyroidism (for a dose of 40 mg see the section "Contraindications");
- own or family anamnesis of muscular diseases (for a dose of 40 mg see the section "Contraindications");
- existence in the anamnesis of a miotoksichnost against the background of reception of other inhibitors of GMG-KOA-reduktazy or fibrat (for a dose of 40 mg see the section "Contraindications");
- an alcohol abuse (for a dose of 40 mg see the section "Contraindications");
the age is more senior than 70 years;
- the states which are followed by increase in concentration of drug in a blood plasma (see the section "Interaction with Other Medicines") (for a dose of 40 mg see the section "Contraindications");
- a concomitant use of fibrat (for a dose of 40 mg see the section "Contraindications").
At such patients it is necessary to estimate a ratio of risk and possible advantage of therapy and to carry out clinical observation throughout all course of therapy.
It is recommended to inform patients on need to immediately report to the doctor about cases of unexpected emergence of muscular pains, muscular weakness or spasms, especially in combination with an indisposition or fever!
At such patients it is necessary to exercise control of activity of KFK surely. Treatment should be stopped if the KFK level more than by 5 times exceeded the upper bound of norm or if muscular symptoms are sharply expressed and cause daily discomfort throughout the day (even if activity of KFK is 5 times less than the upper bound of norm). If symptoms disappear, and activity of KFK is returned to norm, it is necessary to consider a question of repeated purpose of Mertenila® or purpose of alternative inhibitor of GMG-KOA-reduktazy in smaller doses at careful observation of the patient. Regular control of activity of KFK at patients in the absence of symptoms of a rabdomioliz is inexpedient.
However increase in number of cases of a miositis and myopathy was revealed at the patients accepting other inhibitors of GMG-KOA-reduktazy together with derivatives of fibroyevy acid, including gemfibrozit, cyclosporine, niacin in lipidsnizhayushchy doses, antifungal drugs, 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. Therefore the concomitant use of a rozuvastatin and a gemfibrozil is not recommended. The ratio of risk and possible advantage at combined use of a rozuvastatin with fibrata or niacin in lipidsnizhayushchy doses (more than 1 g) has to be carefully estimated. The concomitant use of a rozuvastatin in a dose of 40 mg and fibrat is contraindicated (see the sections "Interaction with Other Medicines" and "Side effect").
Мертенил® patients should not appoint with the acute, serious illness allowing to assume a myopathy or with possible development of a secondary renal failure (for example: sepsis, arterial hypertension, surgical intervention, an injury, a metabolic syndrome, spasms, endocrine disturbances, electrolytic disturbances (see the section "With Care").

As well as the patients who are abusing alcohol or having in the anamnesis of a disease of a liver should appoint other inhibitors of GMG-KOA-reduktazy, Mertenil® with extra care.
It is recommended to carry out definition of indicators of function of a liver to and in 3 months after an initiation of treatment. If activity of "hepatic" transaminases in blood serum by 3 times exceeds the upper bound of norm, it is necessary to stop reception of Mertenila® or to reduce the accepted dose (see the section "Route of Administration and Doses"). Frequency of the expressed abnormal liver functions (connected, generally with increase in activity of "hepatic" transaminases), increases at reception of 40 mg of drug. At patients with a secondary hypercholesterolemia owing to a hypothyroidism, a nephrotic syndrome therapy of a basic disease has to be carried out prior to treatment of Mertenilom®.
During the pharmacokinetic researches increase in system concentration of a rozuvastatin among patients of an Asian origin in comparison with the data obtained among patients - representatives of Caucasian race is revealed (see the section "Route of Administration and Doses" and "Pharmacokinetics").
The concomitant use of a rozuvastatin with inhibitors of proteases is not recommended (see the section "Interaction with Other Medicines").

Influence on ability of control of vehicles and to work with the equipment
Researches on studying of influence of Mertenila® on ability to driving and use of technical means were not conducted. However on the basis of pharmakodinamichesky properties of drug it is possible to assume that Mertenil® should not make such impact. At the same time when driving or other mechanisms it is necessary to consider that during treatment there can be dizziness.

Side effects:

The side effects connected with administration of drug of Mertenil®, usually moderately expressed and short-term. During performing controlled clinical trials less than 4% of the patients accepting розувастатин stopped treatment because of development of side effects.
About side effects in clinical trials and/or experience of use of drug after its commercial implementation it was reported with the following frequency:

- Bodies and systems. Chasto:allergichesky reactions  skin itch, rash, small tortoiseshell Quincke's disease, Stephens-Johnson's syndrome
- Central nervous system: dizziness, headache, asthenic syndrome sleeplessness, change of mood  polyneuropathy, memory loss
- Digestive tract: lock, abdominal pains, nausea  pancreatitis  
- Gepatobiliarny system: jaundice, hepatitis
- Musculoskeletal system: a mialgiya  a myopathy (including a miositis), рабдомиолиз arthralgia
- Urinary system: hamaturia
- Laboratory indicators: increase in activity of "hepatic" transaminases.
As well as at use of other inhibitors of GMG-KOA-reduktazy, the frequency of emergence of side effects has dozozavisimy character.
Frequency of emergence of a rabdomioliz, the expressed side effects from kidneys and a liver increases at patients at reception of a rozuvastatin in a dose of 40 mg.
From an urinary system: at reception of a rozuvastatin the proteinuria, preferential canalicular origin was observed. Changes of protein content in urine (from absence or existence of trace quantities to level ++ above) were found in less than 1% of the patients accepting 10 and 20 mg of a rozuvastatin, and approximately at 3% of the patients accepting drug in a dose of 40 mg.
The minimum change of amount of protein in urine expressed in change from zero level or existence of traces to level + was observed at administration of drug in a dose of 20 mg. In most cases the proteinuria decreased and independently passed in treatment process. In the analysis of these clinical trials the causal relationship between a proteinuria and the acute or progressing diseases of kidneys is not revealed. At a number of the patients who were receiving medical treatment rozuvayetatiny the hamaturia was observed, but data of clinical trials showed that the frequency of emergence of such cases very low.
From a musculoskeletal system: the action on skeletal muscles causing a mialgiya, a myopathy (including a miositis) and in rare instances - рабдомиолиз with development or without development of an acute renal failure, was observed at the patients accepting any dose of a rozuvastatin, in particular a dose it is higher than 20 mg. Increase in maintenance of a kreatinfosfokinaza (KFK) depending on the accepted dose is revealed at the patients accepting розувастатин, but in most cases these manifestations were insignificant, asymptomatic and temporary. If the maintenance of KFK by 5 times exceeds the upper bound of norm, then treatment should be stopped (see the section "Special Instructions").
From a liver: as well as at reception of other inhibitors of GMG-KOA-reduktazy, increase in activity of "hepatic" transaminases depending on the accepted dose was revealed at insignificant number of the patients accepting розувастатин. At the same time in most cases this increase was moderately expressed, asymptomatic and passing.

Interaction with other medicines:

Cyclosporine: at a concomitant use of a rozuvastatin and AUC cyclosporine of a rozuvastatin increased by 7 times in comparison with the values received at healthy volunteers (see the section "Contraindications"). Combined use leads to increase in concentration of a rozuvastatin in a blood plasma by 11 times. At a concomitant use of drugs of change of concentration of cyclosporine in a blood plasma it is not revealed.
Antagonists of vitamin K: as well as in a case with other inhibitors of GMG-KOA-reduktazy, rozuvastatiny or increase in a dose of drug at the patients receiving at the same time antagonists of vitamin K (for example, warfarin or other coumarinic anticoagulants) can lead the beginning of therapy to increase in the international normalized relation (MHO). Cancellation or a dose decline of a rozuvastatin can cause MHO reduction. In such cases it is necessary to carry out MHO monitoring.
Эзетимиб: at a concomitant use of a rozuvastatin and an ezetimib change of AUC or Sshakh of both drugs is not observed. However it is impossible to exclude pharmakodinamichesky interaction of a rozuvastatin and ezetimib capable to cause the undesirable phenomena. Гемфиброзт and other means reducing the level of lipids: the concomitant use of a rozuvastatin and a gemfibrozil leads to increase twice in Cmax and AUC of a rozuvastatin (see the section "Special Instructions").

On the basis of the specific interactions given researches the corresponding pharmacokinetic interaction from fenofibrata, however perhaps pharmakodinamichesky interaction is not expected. Gemfibrozil, фенофибрат, other fibrata and niacin in lipidsnizhayushchy doses (1 g or more in days) at a concomitant use with inhibitors of GMG-KOA-reduktazy increased risk of emergence of a myopathy, it is possible because they can cause a myopathy and at inclusion in monotherapies. The concomitant use of 40 mg of a rozuvastatin and fibrat is contraindicated (see the sections "Special Instructions" and "Contraindications"). At a concomitant use of drug with gemfibrozily and other lipidsnizhayushchy means the initial dose of Mertenila® should not exceed 5 mg.
Inhibitors of proteases: though the exact mechanism of interaction is unknown, the concomitant use of a rozuvastatin with inhibitors of proteases can lead to lengthening of an elimination half-life of a rozuvastatin. In a pharmacokinetic research at a concomitant use of 20 mg of the rozuvastatin and the combined drug containing two inhibitors of proteases (400 mg of a lopinavir / 100 mg of a ritonavir) healthy volunteers revealed increase twice in AUC(0-24) and by 5 times of Cmax of a rozuvastatin, respectively. Therefore at the same time it is not recommended to appoint розувастатин and inhibitors of proteases at therapy of patients with HIV.
Antacids: the concomitant use of a rozuvastatin and antacids in suspension, the containing aluminum or magnesium hydroxide, can lead to decrease in concentration of a rozuvastatin in a blood plasma approximately for 50%. This action is expressed more weakly if antacids are applied in 2 h after reception of a rozuvastatin. The clinical importance of this interaction is not studied.
Erythromycin: the concomitant use of a rozuvastatin and erythromycin can lead to reduction of AUC(0-t) of a rozuvastatin by 20% and Cmax of a rozuvastatin - for 30%. This interrelation can be caused by strengthening of the motility of intestines caused by erythromycin reception.
Peroral kontraiyeptivy/gormonozamestiteljny therapy: the concomitant use of a rozuvastatin and oral contraceptives can lead to increase in AUC ethinylestradiol and Norgestrelum by 26% and 34%, respectively. Such increase in plasma concentration should be considered at the choice of a dose of oral contraceptives. Pharmacokinetic data on simultaneous use of a rozuvastatin and drugs of gormonozamestitelny therapy are absent therefore it is impossible to exclude similar action when using this combination. However such combination of drugs was rather widely used by women during conduct of clinical trials and well transferred.

Other medicines: clinically significant interaction at a concomitant use of a rozuvastatin and digoxin is not expected.
P450 cytochrome isoenzymes: results of the conducted researches in vitro and in vivo showed what розувастатин is not either inhibitor, or the inductor of isoenzymes of P450 cytochrome. Besides, розувастатин is rather weak substrate for these enzymes. Clinically significant interaction between rozuvastatiny and flukonazoly (inhibitor of isoenzymes of CYP2C9 and CYP3A4) or ketokonazoly was not revealed (inhibitor of isoenzymes of CYP2A6 and CYP3A4). Combined use of an itrakonazol (CYP3A4 isoenzyme inhibitor) and a rozuvastatin increases AUC of a rozuvastatin by 28% (clinically not significantly). Therefore any interaction of medicines connected with metabolism by P450 cytochrome is not expected.

Contraindications:

For mg tablets 5,10 and 20: hypersensitivity to a rozuvastatin or any of drug components;
- liver diseases in an active phase, including permanent increase in activity of "hepatic" transaminases, and also 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 the patients predisposed to development of miotoksichesky complications;
- pregnancy and period of a lactation;
- at the women of childbearing age who are not applying well-tried remedies of contraception;
- age up to 18 years (efficiency and safety are not established);
- to patients with a liver failure with point higher than 9 on a scale of Chayld-Pyyu;
- lactose intolerance, deficit of lactase or glyukozo-galaktozny malabsorption.

For tablets of 40 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 also 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 60 ml/min.);
- myopathy;
- concomitant use of cyclosporine;
- at the patients predisposed to development of miotoksichesky complications;
- pregnancy and period of a lactation;
- hypothyroidism;
- 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;
- states which can lead to increase in concentration of a rozuvastatin in a blood plasma;
to patients of Asian race;
- concomitant use of fibrat;
- age up to 18 years (efficiency and safety are not established);
- to patients with a liver failure with point higher than 9 on a scale of Chayld-Pyyu;
- lactose intolerance, deficit of lactase or glyukozo-galaktozny malabsorption.

With care
For mg tablets 5,10 and 20
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; states at which increase in plasma concentration of a rozuvastatin is noted; the age is more senior than 70 years; liver diseases in the anamnesis; sepsis; arterial hypotension; extensive surgical interventions; injuries; heavy metabolic, endocrine or electrolytic disturbances; uncontrollable epilepsy; race (Asian race); concomitant use of fibrat.

For tablets of 40 mg
Existence of risk of development of a myopathy / рабдомиолиза - a renal failure; the age is more senior than 70 years; liver diseases in the anamnesis; sepsis; arterial hypotension; extensive surgical interventions; injuries; heavy metabolic, endocrine or electrolytic disturbances, uncontrollable epilepsy.

Use at pregnancy and in the period of a lactation
Мертенил® it is contraindicated to use at pregnancy and in the period of a lactation. Women of childbearing age should apply reliable and adequate contraceptives.
As cholesterol and products of biosynthesis of cholesterol are of great importance for fetation, the potential risk of inhibition of GMG-KOA-reduktazy exceeds advantage of its use at pregnancy.
In case of pregnancy emergence administration of drug should be stopped immediately. Data on release of drug with breast milk are absent. In need of purpose of drug in the period of a lactation breastfeeding needs to be stopped.

Overdose:

Specific treatment at overdose does not exist.
In case of overdose it is recommended to hold a symptomatic treatment and the supporting events. It is necessary to control function of a liver and a degree of activity of KFK. The hemodialysis in this case is probably ineffective.

Storage conditions:

In the dry, protected from light place at a temperature not above 30 °C. To store in the place, unavailable to children!

Issue conditions:

According to the recipe

Packaging:

Tablets film coated 5 mg, 10 mg, 20 mg and 40 mg. On 10 tablets of 5 mg, film coated with a dosage; 10 mg; 20 mg and 40 mg in a blister strip packaging from a foil of PAS / It is scarlet / PVC and the printing aluminum foil varnished.
On 3 blister strip packagings for tablets with a dosage of 5 mg, 10 mg, 20 mg and 40 mg together with the application instruction place in a pack from a cardboard.