Inedzhi

General characteristics. Structure:

Active agents: 10 mg of an ezetimib and 10 mg, 20 mg, 40 or 80 mg of a simvastatin.

Excipients: lactoses monohydrate, cellulose microcrystallic, gipromelloza of 2910 6 cps, sodium of a kroskarmelloz, citric acid monohydrate, butylhydroxyanisole, propyl gallate, magnesium stearate.

Pharmacological properties:

INEDZhI is hypolipidemic drug which reduces absorption of cholesterol and related vegetable sterol in intestines, and also suppresses endogenous synthesis of cholesterol.

Pharmacodynamics. Inedzhi.Kholesterin comes to a blood plasma as a result of intestinal absorption and endogenous synthesis. Inedzhisoderzhit эзетимиб and симвастатин, two hypolipidemic components supplementing each other with the mechanism of action. INEDZhI reduces the increased level of the general cholesterol, lipoproteins of the low density (LPNP), apolipoproteins B (Aro In), triglycerides (TG) and lipoproteinovnevysoky density (ne-LPVP), and increases the level of lipoproteins of the high density (LPVP) by a dvoynogoingibirovaniye: absorption and synthesis of cholesterol.

ЭЗЕТИМИБ.Механизм actions of an ezetimib differs from other classes of hypolipidemic means (for example, statines, sekvestrant of bile acids, fibrat). Эзетимиб at receipt in a small intestine slows down cholesterol absorption that brings to a cholesterol umensheniyupostupleniya from intestines into a liver. After 2-week use эзетимиб reduces absorption of cholesterol in intestines by 54% in comparison with placebo. A number of preclinical trials of an ezetimib confirms its selectivity in decrease in absorption of cholesterol. Эзетимиб slows down absorption [14C] - cholesterol, and does not affect absorption of triglycerides, жирныхкислот, bile acids, progesterone, acetenyl in any way - oestradiol or fat-soluble vitamins A and D.

СИМВАСТАТИН.Симвастатин after intake in the form of a neaktivnogolakton is exposed to hydrolysis with education corresponding b-hydroxyacid derivative, having the high inhibiting activity concerning HMG-CoA reductase (3 hydroxies - 3 metilglyutarilko of reductase). This enzyme starts initial inaiboly a significant stage of biosynthesis of cholesterol conversion GMG-KOA in мевалонат. Simvastatin снижаеткак raised, and normal levels концентрацийЛПНП. LPNP are formed of proteins of very low density (LPONP) and Lpnp.Snizheny LPNP after reception of a simvastatin are exposed to splitting preferential by means of a vysokoafinny receptor gives a kumensheniya of maintenance of LPONP and activation of LPNP-receptors that leads to reduction of education and strengthening of a catabolism of LPNP. At therapy симвастатиномуровень Aro In also decreases. Besides, simvastatinumerenno increases the LPVP level and reduces plazmykrova TG. As a result of these changes the level of the general cholesterol and LPNP decrease.

Pharmacodynamics. INEDZhI биоэквивалентен combinations of an ezetimib and simvastatin. At a concomitant use of an ezetimib and a simvastatin clinically significant pharmacokinetic interaction was not revealed.

ВСАСЫВАНИЕ.ЭЗЕТИМИБ.После intake эзетимиб it is quickly soaked up and intensively conjugates in pharmacological active phenolic glucuronide (ezetimib-glucuronide). The maximum concentration (Cmax) of an ezetimib in plazmekrov after administration of drug is inside reached cherez4-12 hours. Absolute bioavailability of an ezetimib cannot be defined as it is insoluble in one izvodny solvents used for injections. Meal (with the low or high content of fat) does not influence bioavailability of an ezetimib at intake, in particular in the form of tablets of 10 mg.

The b-hydroxyacid Simvastatin.Biodostupnost after reception of a simvastatin inside makes less than 5% of a dose. In addition to? hydroxyacids in a blood plasma are found 4 more active metabolites. Meal does not exert impact on plasma concentration of active and general metabolites of a simvastatin.

РАСПРЕДЕЛЕНИЕ.ЭЗЕТИМИБ.Эзетимиб and an ezetimib-glucuronide contact proteins of a blood plasma for 99,7% and 88-92% respectively.

СИМВАСТАТИН.Симвастатин and b-hydroxyacid contact proteins of a blood plasma for 95%. Pharmacokinetic researches showed what симвастатин does not collect in fabrics after reception of repeated doses. The maximum level of metabolites in a blood plasma is observed in 1,3-2,4 hours after administration of drug.

МЕТАБОЛИЗМ.ЭЗЕТИМИБ.Первичный metabolism of an ezetimib happens in a small intestine and a liver by conjugation to a glucuronide (reaction of the II phase), to the subsequent allocation with bile. The minimum oxidizing metabolism (reaction of the I phase) was observed at all stages of transformation of an ezetimib. Эзетимиб and the ezetimib-glucuronide, the main derivatives of drug, make 10-20% and 80-90% of the general content of drug in a blood plasma respectively. Эзетимиб and an ezetimib-glucuronide are slowly brought out of a blood plasma in the course of enterohepatic recirculation. The elimination half-life for an ezetimib and an ezetimibglyukuronid makes about 22 hours.

СИМВАСТАТИН.Симвастатин - an inactive lactone which is quickly hydrolyzed by in vivo in the corresponding b-hydroxyacid, powerful inhibitor of HMG-CoA reductase. Hydrolysis generally happens in a liver; hydrolysis speed in a blood plasma very low. Simvastatin is well soaked up and almost completely metabolized already at "the first passing" through a liver. Capture of a simvastatin a liver is defined by the speed of a hepatic blood-groove. The main metabolism happens in a liver, metabolites of u1087 of drug are removed with bile. Therefore amount of active drug in a system blood-groove very insignificant.

ВЫВЕДЕНИЕ.ЭЗЕТИМИБ.После intake of 20 mg of an ezetimib, marked 14C, in a blood plasma 93% of a total ezetimib of the general level of radioactive products were revealed. About 73% and 11% according to the accepted radioactive products were removed through intestines and kidneys within 10 days. In 48 hours of radioactive products in a blood plasma it was revealed not.

SIMVASTATIN.V techenie is 96 hours old after intake of a radioactive simvastatin, 13% of radioactive products were removed by kidneys, and 60% - through intestines. After intravenous administration of a metabolite of b-hydroxyacid only 0,3% of the entered dose were removed by kidneys in the form of metabolites.

Pharmacokinetics at special groups of patients.

Deti.Farmakokinetichesky data, absorption and metabolizmezetimiba are identical at children / teenagers (10-18 years) of ivzrosly. There are no data on drug pharmacokinetics at a deteymladsha of 10 years. The clinical use of drug to vpediatrichesky practice (children and teenagers have 9-17 years) is limited to data on patients with a homozygous family hypercholesterolemia (GOSG) or a homozygous sitosterinemiya (hyper - апо - beta lipoproteinemiyey).

ELDERLY PATIENTS. At elderly patients (65 years are more senior) concentration of the general ezetimib in a blood plasma approximately twice higher, than at younger patients (18-45 years). Level of decrease in LPNP and profiles of safety at the elderly and younger patients accepting эзетимиб are approximately identical.

PATIENTS WITH HEPATIC NEDOSTATOCHNOSTYYU.POSLE of a single dose of an ezetimib of 10 mg average value of the area under curve (AUC) for the general ezetimibabylo in 1,7 are higher at patients with a slight liver failure (5-6 points on a scale of Chayld-Pyyuga), than upatsiyent with the kept function of a liver. In a 14-dnevnomissledovaniye of an ezetimib in a dose of 10 mg a day from uchastiyempatsiyent with a moderate liver failure (7-9ball on a scale of Chayld-Pyyuga) average AUC value of a dlyaobshchy ezetimib increased by 4 times on the 1st and 14th denpo to comparison with patients with the kept function of a liver. For patients from an easy hepatic nedostatochnostyyukorrektion of a dose it is not required. As effects of the increased concentration of a total ezetimib are unknown, эзетимиб is not recommended to patients with moderate and heavy (more than 9 points on a scale of Chayld-Pyyuga) a pechenochnoynedostatochnost (see the section With CARE).

PATIENTS WITH RENAL NEDOSTATOCHNOSTYYU.EZETIMIB.POSLE of a single dose in an ezetimib of 10 mg average AUC at patients with a heavy renal failure (average clearance of creatinine <30 ml/min./1,73 sq.m) increased by 1,5 times in comparison with healthy patients.

SIMVASTATIN.V a research of patients with a heavy renal failure (the clearance of creatinine (CC) less than 30 ml/min.) after reception of inhibitors of HMG-CoA reductase the general concentration of metabolites of a simvastatin was twice higher, than at healthy volunteers.

Pol.Obshchy concentration of an ezetimib is a little higher (20%) at women, than at men. Level of decrease in LPNP and profiles of safety are approximately identical at the men and women accepting эзетимиб.

Indications to use:

PRIMARY HYPERCHOLESTEROLEMIA. ИНЕДЖИ it is shown to patients with primary (heterozygous family and single) a hypercholesterolemia or the mixed lipidemia as addition to a diet for the purpose of decrease in level of the general cholesterol, lipoproteins of low density, an apoliprotein In, triglycerides, lipoproteins of low density, and for increase in level of lipoproteins of high density.

HOMOZYGOUS FAMILY HYPERCHOLESTEROLEMIA (GOSG). INEDZhI is shown for decrease in the increased level of the general cholesterol and LPNP at patients with GOSG, as as additional treatment to other hypolipidemic therapy (for example, LPN-afereza), and at its absence.

Route of administration and doses:

Prior to therapy to pass with drug INEDZhI of a patsiyentydolzhna to a gipokholesterinemichesky diet to isoblyudat it throughout all course of treatment. INEDZhI is accepted once a day, in the evening, независимоот meal.

The dosage depends on the LPNP initial level, the purpose of treatment and therapeutic effect and can vary from 10/10 mg (10 mg of an ezetimib + 10 mg of a simvastatin) do10/80 mg (10 mg of an ezetimib + 80 mg of a simvastatin) in day. The starting dose of 10/20 mg (10 mgezetimib + 20 mg of a simvastatin) in day is usually recommended. For gradual decrease in the LPNP level the bytrekomendovana a mg drug 10/10 dose can (10 mg of an ezetimib + 10 mg of a simvastatin). For considerable decrease in LPNP (more, than for 55%), to patients therapy with dozy10/40 can be recommended to mg (10 mg of an ezetimib + 40 mg of a simvastatin) in day. In 2 weeks after an initiation of treatment, and also throughout all course of treatment, follows контролироватьуровень lipids, and if necessary - to a drug skorrektirovatdoz.

To PATIENTS WITH PRIMARY HYPERCHOLESTEROLEMIA. ИНЕДЖИ it is recommended to accept daily in doze10/40 mg (10 mg of an ezetimib + 40 mg of a simvastatin) ili10/80 mg (10 mg of an ezetimib + 80 mg of a simvastatin) in the evening for decrease in the increased level of an obshchegokholesterin, LPNP, an apoliprotein In, triglycerides ine-LPVP, and also for increase in the LPVP level to patients with primary (heterozygous family and single) a hypercholesterolemia or the mixed dislipidemiya. Therapy is carried always out against the background of a gipokholesterinemichesky diet. For further decrease in the TG levels ine-LPVP and increases in LPVP patients with a smeshannoydislipidemiya can have a treatment of INEDZhI dopolnenofenofibraty.

PATIENTS WITH HOMOZYGOUS FAMILY GIPERKHOLESTERINEMIYEY.PATSIYENTAM with a homozygous family hypercholesterolemia is recommended to accept INEDZhI once in sutki10/40 mg or 10/80 mg in the evening. INEDZhI долженприменяться at these patients in combination with other hypolipidemic therapy (for example, LPNP аферез). Prinevozmozhnosti of carrying out additional lecheniyainedzh can be appointed as monotherapy.

USE FOR ELDERLY of PATSIYENTOV.DL of elderly patients is not required to dose adjustment (see Pharmacokinetics from special groups of patients).

USE FOR PATIENTS FROM HEPATIC of NEDOSTATOCHNOSTYYU.DL of patients with easy degree of a liver failure (5-6 points on a scale of Chayld-Pyyuga) korrektsiidoza is not required. INEDZhI is not recommended пациентамс moderated (7-9 points on a scale of Chayld-Pyyuga) or heavy degree (more than 9 points on a scale of Chayld-Pyyuga) to a liver failure (see sections of the CONTRAINDICATION and Pharmacokinetics at special groups of patients).

USE FOR PATIENTS FROM RENAL of NEDOSTATOCHNOSTYYU.DL of patients with moderate degree of a renal failure is not required to dose adjustment. In need of therapy at patients with the expressed renal failure (KK <30 ml/min.) drug in a dose more 10/10mg in day has to be used with care (see sections With CARE and Pharmacokinetics at особыхгрупп patients).

USE WITH OTHER MEDICINAL MEANS. ИНЕДЖИ it is necessary to accept at least for 2 часадо or in 4 hours after reception of sekvestrant желчныхкислот. For the patients accepting niacin to a vdoza> 1 g a day, cyclosporine or даназол, the dose of INEDZhI should not exceed 10/10 mg a day (see разделВЗАИМОДЕЙСТВИЕ With OTHERS LEKARSTVENNYMISREDSTVAMI). For the patients accepting Amiodaronum or verapamil, the dose of INEDZhI should not exceed 10/20 mg a day (see the section INTERACTION WITH OTHER MEDICINES).

Features of use:

HEAVY RENAL NEDOSTATOCHNOST.PRI of need of therapy of INEDZhI at patients with the expressed renal failure (KK <30 ml/min.) drug in a dose more than 10/10 mg a day has to be used with care.

HEPATIC INSUFFICIENCY. ИНЕДЖИ it has to be applied with care at the patients who are accepting alcohol in large numbers, and/or having liver diseases in the anamnesis. Acute diseases of a liver or it is inexplicable the steady high level of activity of enzymes of a liver are contraindications to administration of drug (see the SECTION of the CONTRAINDICATION).
INEDZhI is not recommended to patients with a moderate or heavy liver failure (see Pharmacokinetics at special groups of patients).

SURGICAL ВМЕШАТЕЛЬСТВО.Контингент patients with the burdened anamnesis demands careful observation during treatment by drug INEDZhI. Administration of drug is recommended to be stopped temporarily some days before performing big surgeries and in the early postoperative period.

Myopathy / рабдомиолиз. Simvastatin, as well as other inhibitors of GMG-KOA-reduktazy, can cause the myopathy (see. With CARE) which is shown muscular pains, weakness, exhaustion, an atakzha increase in level of a kreatinfosfokinaza more чемв 10 times of rather upper bound of norm. Sometimes the myopathy takes the form of a rabdomioliz and can be followed by a myoglobinuria, an acute renal failure, and in rare instances - a lethal outcome. The risk miopatiiuvelichivatsya due to increase in a blood plasma of the inhibiting activity concerning GMG-KOA-reduktazy. Riskmiopatiya increases at the combined reception of INEDZhI and some medicines therefore the decision of an onaznacheniya of INEDZhI has to be made individually suchety specific circumstances (see VZAIMODEYSTVIYES OTHER MEDICINES). The majority of cases of a rabdomioliz against the background of lecheniyasimvastatiny was combined with the burdened anamnesis, including a renal failure, preimushchestvennodiabetichesky genesis. The contingent of patients with the burdened anamnesis demands careful observation of treatment by drug ИНЕДЖИ.Риск of development of a myopathy / рабдомиолиза in time depends on a dozysimvastatin. In clinical trials, in a kotorykhsostoyaniye of patients it was carefully controlled, a myopathy / рабдомиолиз were observed: at reception of 20 mg of a simvastatin approximately in 0,03% of cases, at reception of 40 mg of a simvastatin - in 0,08%, at reception of 80 mg of a simvastatin - v0,4% of cases. At the beginning of reception or at increase дозыИНЕДЖИ patients have to be warned about a riskemiopatiya and need to immediately tell the doctor of an ovozniknoveniya of inexplicable muscular pains, slabostiit indispositions. Therapy of INEDZhI has to be immediately stopped when diagnosing or a podozreniin a myopathy. Existence of these symptoms and/or increase of level of a kreatinfosfokinaza more than by 10 times. an above-upper limit of norm, means existence of a myopathy. To Vbolshinstva of cases, at the termination of reception of a simvastatin symptoms of a myopathy and the increased u1082 level of a kreatinfosfokinaza disappeared. At the beginning of reception or a uvelicheniyadoza of INEDZhI periodic control of level of a kreatinfosfokinaza can be required, but this measure not to mozhetgarantirovat the prevention of development of a myopathy.

Influence on ability to drive the car or work with the equipment. Researches for impact assessment on ability to drive the car or work with the equipment were not conducted. However there are no bases to assume that INEDZhI can influence these processes somehow.

Side effects:

Safety of drug INEDZhI is studied in klinicheskikhissledovaniye with participation more than 3800 patients and in hodepostmarketingovy observations in the different countries. In the whole INEDZhI it is well transferred by patients. Side effects at reception of INEDZhI are comparable spobochny effects about which it was reported to a pripriyoma of an ezetimib and/or a simvastatin earlier. According to placebo of controlled researches and during post-marketing observation at patients at reception ИНЕДЖИбыли the following characteristic side effects with a frequency> 1/100 and <1/1,0 as connected with administration of drug, and without accurately established connection are noted:

The general: increased fatigue.
- From digestive tract: meteorism, abdominal pains, diarrhea
- From blood and lymphatic system: thrombocytopenia
- From gepatobiliarny system: cholelithiasis, cholecystitis, hepatitis
- From skeletal and muscular system: mialgiya,
arthralgia and very seldom myopathy / рабдомиолиз
- From a nervous system: dizziness, headache
- From laboratory indicators: increase in level of a kreatinfosfokinaza and activity of "hepatic" enzymes
- From skin and a hypodermic fatty tissue: hypersensitivity reactions, including skin rash and a small tortoiseshell (it is rare [> 1/10000, <1/1000]), and also anaphylactic reactions and a Quincke's disease (it is very rare [<1/10000])
- From a digestive tract: nausea (seldom), pancreatitis (very seldom)
- From the general disturbances: adynamy
- From blood and lymphatic system: anemia
- From a digestive tract: abdominal pain, lock, diarrhea, dyspepsia, nausea, vomiting, pancreatitis
- From gepatobiliarny system: hepatitis / jaundice and seldom or never - a liver failure.

LABORATORY INDICATORS. According to the controlled combined clinical trials clinically significant increase in transaminases of blood serum (ALT and/or ACT by 3 times and more) was noted at 1,7% of the patients accepting INEDZhI.
These changes were asymptomatic, did not lead to a cholestasia, and took place independently at the termination or continuation of treatment. At 0,2% of the patients accepting drug INEDZhI clinically significant increase in a kreatinfosfokinaza (exceeding the upper bound of norm in 10 and more times) was observed.

Interaction with other medicines:

At the combined use of INEDZhI, especially in high doses, and powerful CYP3A4 inhibitors for example, an itrakonazola, a ketokonazola, erythromycin, a klaritromitsin, the telitromitsina, inhibitors of HIV protease, a nefazodon, increases risk of development of a myopathy / рабдомиолиза. If therapy itrakonazoly, ketokonazaly, erythromycin, klaritromitsiny or a telitromitsinomneobkhodima, then during this therapy to stop Inedzhineobkhodimo's reception. It is necessary to avoid a concomitant use of drug with other medicines containing strong ingibitorycyp3a4 if only advantages of a combination therapy do not exceed potential risk.

GEMFIBROZIL And OTHERS FIBRATY:PRI the combined reception of INEDZhI and fenofibrataila was gemfibrozit by concentration of an ezetimib in a blood plasma increases in 1,5 and 1,7 times respectively; however such increase is not clinically significant. Safety and efficiency of INEDZhI in a sfibratama combination (except for a fenofibrat) nedostatochnoizuchena. In a research in which 184 patients accepting INEDZhI in a dose 10/20mg in day of an ifenofibrat in a dose of 160 mg within 12 weeks, not bylootmecheno the undesirable phenomena from outside желчногопузыря participated. It is supposed that fibrata can a cholesterol uvelichivatvydeleniye in bile that in turn can lead to cholelithiasis.

TSIKLOSPORIN, DANAZOL OR NIKOTINOVAYA KISLOTA in a dose> 1 g a day: at the combined use with INEDZhI, especially in high doses, the risk of development of a myopathy / рабдомиолиза increases. INEDZhI in combination with niacin (> 1 g a day) should appoint with care since niacin as monotherapy can cause a myopathy. For the patients accepting cyclosporine or даназол in a dose> 1 g a day, the dose of INEDZhI should not exceed 10/10 mg day. Advantages of use of INEDZhI for the patients accepting cyclosporine or даназол have to be carefully estimated in relation to potential risk of similar combinations. At purpose of INEDZhI in combination with cyclosporine constant control of concentration of cyclosporine in blood is necessary.

AMIODARONUM OR VERAPAMIL.PRI the combined reception with INEDZhI, especially in high doses, increases risk of development of a myopathy / рабдомиолиза. There are myopathies given about development at 6%patsiyentov, participating in sootvetstvuyushchikhklinichesky researches and receiving симвастатинв to a dose of 80 mg and Amiodaronum.
For patients, принимающихамиодарон or verapamil, a dose of INEDZhI should not exceed 10/20 mg a day. It is necessary to avoid the combined use of INEDZhI in the doses exceeding 10/20 mg a day with Amiodaronum or verapamil if only advantages of the combined therapy do not exceed potential risk of a myopathy.

FUZIDOVY ACID. At the patients accepting fuzidovy acid along with INEDZhI the risk of development of a myopathy therefore it is necessary to trace a condition of such patients attentively can increase.

DILTIAZEM.U of the patients accepting diltiazem and INEDZhI in a dose of 10/80 mg risk of development of a myopathy increases slightly. Clinical trials showed that the risk of a myopathy is identical at the patients accepting симвастатин in a dose of 40 mg with the accompanying therapy by diltiazem or without it.

CYP3A4 INHIBITORS. Preclinical trials showed what эзетимиб does not induce CYP3A4 isoenzymes. Clinically significant pharmacokinetic interaction between ezetimiby and other means using isoenzymes of system of P450 1A2, 2D6, 2C8, 2C9 cytochrome, and ZA4 or enzymes of N-acetyltransferases in metabolism was not revealed. Simvastatin is metabolized by CYP3A4 isoenzyme, but has no the SURZA4-inhibiting activity therefore its impact on plasma concentration of other drugs, metabolized CYP3A4 isoenzyme, is improbable. Strong inhibitors of an isoenzyme CYP3A4 increase risk of a myopathy as interfere with removal of a simvastatin.

КОЛЕСТИРАМИН.При the combined use with Colestyraminum average AUC value of a total ezetimib (an ezetimib and an ezetimib of a glucuronide) decreased approximately by 55%. At the combined use of INEDZhI and Colestyraminum the accruing decrease in LPNP can decrease.

VIDA VZAIMODEYSTVIYA.SOK of grapefruit contains OTHERS one or more components inhibiting CYP3A4 isoenzyme and can increase the level of substances, metaboliziruyemy CYP3A4 in a blood plasma. The effect of the use of juice in small amounts (250 ml a day) - is minimum (the activity inhibiting HMG-CoA reductase increases in a blood plasma for 13% as shows AUC value) and has no clinical importance. u1054 However the use of a large amount of juice (more than 1 l a day) during reception of a simvastatin considerably increases the level of the activity inhibiting HMG-CoA reductase in a blood plasma. Therefore it is necessary to avoid the simultaneous use of large numbers of grapefruit juice and INEDZhI.

COUMARIN DERIVATIVES (ANTICOAGULANTS). In two clinical trials (one - at healthy volunteers, another - at patients with a hypercholesterolemia) симвастатин in a dose of 20-40 mg a day the effect of coumarinic anticoagulants moderately potentiated, extending a prothrombin time when the reference value of MHO (the international normalized relation - otnosheniyaprotrombinovy time of the patient to protrombinovomuvremen of a normal blood plasma) 1,7 at healthy volunteers increased to 1,8, and at patients with a hypercholesterolemia initial 2,6 - increased to 3,4. To the patients accepting coumarinic anticoagulants, provodyattshchatelny control of indicators of coagulant system of blood (prothrombin time) to the first a priyemainedzha. The subsequent measurements have to be regular before achievement of stable indicators of MHO, then take measurements with the usual frequency recommended for control at treatment by coumarinic anticoagulants. At drug withdrawal and change of a dose of INEDZhI carry out extraordinary determination of parameters of coagulability of blood. Therapy to the simvastatinoyena caused in the patients who are not accepting anticoagulants bleedings or changes of a parametrovsvertyvayemost of blood.

Antatsidy.Sovmestny reception of INEDZhI and antacids slightly reduces the level of absorption of an ezetimib, but does not influence its bioavailability.

Contraindications:

- hypersensitivity to any component of drug;
- liver diseases in an active phase or permanent increase in activity of transaminases of the LIVER of not clear etiology;
- moderate and heavy degree of a liver failure (7 and more points on a scale of Chayld-Pyyuga);
- pregnancy or period of a lactation;
- age up to 18 years.

With care. The expressed renal failure (KK less than 30 ml/min.), an alcohol abuse, liver diseases in the anamnesis, painful feelings in muscles or change of a tone of skeletal muscles of not clear etiology, a disease of a gall bladder at co-administration of INEDZhI from fibrata.

Overdose:

СИМВАСТАТИН.Сообщалось about several cases of overdose simvastatiny without clinically significant effects for patients; the maximum accepted dose made 3,6 g.

EZETIMIB.V clinical trials of 15 healthy patients accepting эзетимиб in a dose of 50 mg to day for 14 days, and 18 patients with primary hypercholesterolemia accepting эзетимиб in a dose of 40 mg a day for 56 days well transferred drug. It was reported about several cases of overdose; in most cases the overdose did not cause the undesirable phenomena. The undesirable phenomena which took place were not serious.

ИНЕДЖИ.Нет of specific treatment of overdose of u1087 drug INEDZhI. In case of overdose it is recommended to carry out the symptomatic and supporting treatment.

 

Storage conditions:

List B. In the place, unavailable to children, at a temperature not above 30 °C.

Issue conditions:

According to the recipe

Packaging:

Dosage of 10 mg / 10 mg:
On 100 tablets in a bottle from polyethylene of high density, on one bottle together with the application instruction in a cardboard pack.
On 7, 10 or 14 tablets in the blister from PVC / aluminum foil. On 1,2, 3, 4, 5, 8,10, 14, or 30 blisters together with the application instruction in a cardboard pack.

Dosage of 10 mg / 20 mg; 10 mg / 40 mg and 10 mg / 80 mg:
On 10 or 14 tablets in the blister from PVC / aluminum foil.
On 3, 5 or 10 blisters together with the application instruction in a cardboard pack.