Egilok Retard

General characteristics. Structure:

Tablets of 1 tab. - метопролол tartrate of 25 mg; 50 mg; 100 mg;
excipients: MKTs; sodium carboxymethylstarch; silicon dioxide colloid anhydrous; povidone; magnesium stearate  
in banks of dark glass 30 or 60 of piece; in a pack of cardboard 1 bank.
Egilok Retard

Tablets, coated, the prolonged action of 1 table.
метопролол tartrate of 50  mg 100 mg
excipients: polyethylene oxide; butyl hydroxytoluene; MKTs; silicon dioxide colloid anhydrous; povidone; sodium of a stearil fumarates; gipromelloza; titanium E171 dioxide; talc; macrogoal 6000  
in the blister of 10 pieces; in a pack cardboard 1, 2 or 3 blisters.
Description of a dosage form

Egilok
Tablets of 25 mg: white or almost white, round, biconvex tablets, with the crosswise dividing line and a double bevel on one party and an engraving "Е 435" — on another, inodorous.
Tablets of 50 mg: white or almost white, round, biconvex tablets, with risky on one party and an engraving "Е 434" — on another, inodorous.
Tablets of 100 mg: white or almost white, round, biconvex tablets, with risky on one party and an engraving "Е 432" — on another, without or almost inodorous.
Egilok Retard
Tablets of 50 mg: white, oblong shape, biconvex with dividing risky on both parties, without or almost inodorous.
Tablets of 100 mg: white, round, biconvex, with an engraving "100" on one party and with dividing risky — on both sides; without or almost inodorous.

Pharmacological properties:

Pharmacological action - anti-anginal, hypotensive, antiarrhytmic.

Pharmacokinetics. Egilok
Quickly and completely (95%) it is soaked up in a GIT. Cmax in a blood plasma is reached in 1,5–2 h after intake. T1/2 averages 3,5–7 h.
Bioavailability makes 50%. During treatment bioavailability increases up to 70%. Meal increases bioavailability for 20–40%. Bioavailability increases at cirrhosis.
The volume of distribution makes 5,6 l/kg. Linkng with proteins of a blood plasma of 12%.
Gets through GEB and a placental barrier. It is allocated in breast milk in insignificant quantities.
It is metabolized in a liver. Metabolites have no pharmacological activity. About 5% of drug are removed in not changed look by kidneys. Treatment of patients with reduced function of kidneys does not demand drug dose adjustment. The abnormal liver function slows down drug metabolism, and in cases of a liver failure the dose of drug has to be lowered. Is not removed at a hemodialysis.
Egilok Retard
Absorption
Metoprolol is soaked up from a GIT almost completely (95% of the dose accepted inside). Extent of absorption differs depending on a dosage form, besides, the free fraction of a metoprolol increases at its reception together with food. After purpose of a metoprolol ретард its absorption is significantly extended, providing a uniform profile of concentration of drug in blood and relative bioavailability> 80%, in comparison with the schedule of change of content of drug, dependent on time, in blood after reception of a usual dosage form. Cmax of drug in blood is noted in 2–6 h after reception. Influence of food on pharmacokinetics of the prolonged form of a metoprolol insignificant.
Distribution
The volume of distribution makes 5,6 l/kg. Linkng with proteins of a blood plasma of 12%.
Metabolism
Metabolites have significantly lower pharmacological activity and toxicity in comparison with initial connection.
Removal
T1/2 of a metoprolol to 9,5 h Metoprolol is almost completely removed with urine for 72 h. About 3% are removed in not changed look. At patients with an impaired renal function T1/2 and the general clearance of a metoprolol significantly do not differ. At a heavy liver failure of T1/2 of a metoprolol increases in this connection the dose of drug should be lowered.

Pharmacodynamics. Blocking heart beta1-adrenoceptors in low doses, reduces stimulated catecholamines formation of tsAMF from ATP, reduces intracellular current of Sa2+, renders negative hrono-, dromo-, batmo-and inotropic action (urezhat ChSS, conductivity and excitability oppresses, reduces contractility of a myocardium).
OPSS at the beginning of use of beta adrenoblockers (in the first 24 h after oral administration) — increases (as a result of reciprocal increase of activity of alpha adrenoceptors and elimination of stimulation of beta2-adrenoceptors), in 1–3 days is returned to initial, and at long appointment — decreases.
Hypotensive action is caused by reduction of cordial emission and synthesis of a renin, activity oppression a system renin-angiotenzinovoy (has bigger value at patients with initial hypersecretion of a renin) and TsNS, recovery of sensitivity of baroreceptors of an aortic arch (there is no strengthening of their activity in response to decrease in the ABP) and, as a result, reduction of peripheral sympathetic influences. Reduces raised by the ABP at rest, at a physical tension and a stress.
The anti-anginal effect is defined by decrease in need of a myocardium for oxygen as a result of reduction of ChSS (lengthening of a diastole and improvement of perfusion of a myocardium) and contractility, and also decrease in sensitivity of a myocardium to influence of a sympathetic innervation. Reduces number and weight of attacks of stenocardia and increases portability of an exercise stress.
Prevents development of migraine.
At use in average therapeutic doses, exerts less expressed impact on the bodies containing beta2-adrenoceptors (a pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchial tubes and a uterus) and on carbohydrate metabolism. At long-term reception reduces the content of cholesterol in blood. At use in high doses (> 100 mg/days) the blocking effect renders on both subtypes of beta adrenoceptors.
Egilok
The ABP decreases in 15 min., as much as possible — in 2 h and remains lowered during 6 h, DAD changes more slowly: stable decrease is observed after several weeks of regular reception.
The antiarrhytmic effect is caused by elimination of aritmogenny factors (tachycardia, a superactivity of a sympathetic nervous system, the increased maintenance of tsAMF, arterial hypertension), reduction of speed of spontaneous excitement of sinus and ectopic pacemakers and delay of AV of conductivity (it is preferential in antegrade and, to a lesser extent, in retrograde the directions through an AV node) and on additional ways.
At supraventricular tachycardia, atrial fibrillation, sinus tachycardia at functional heart diseases and a hyperthyroidism, urezhat ChSS or can even lead to recovery of a sinoatrial rate.
Egilok Retard
Represents a dosage form of long action.
Reduces automatism of a sinus node, urezhat ChSS, conductivity slows down AV, reduces contractility and excitability of a myocardium, cordial emission, reduces the need of a myocardium for oxygen. Suppresses the stimulating effect of catecholamines on heart at exercise and psychoemotional stress.
Drugs of a metoprolol of long release provide desirable clinical effect at convenient single appointment in day. Advantage of drug of a metoprolol of long release is connected with higher cardioselectivity of drug in low concentration in blood. Purpose of a metoprolol in a dosage form of controlled release in the same or even smaller doses, as ordinary drug, gives comparable therapeutic effect at much lower peak of concentration of substance in blood. It significantly reduces the side effects connected with blockade beta адренорецепоров extracardiac localization.

Indications to use:

For both dosage forms:
arterial hypertension (in monotherapy or in a combination with other anti-hypertensive drugs);
Ischemic heart disease: myocardial infarction (secondary prevention), prevention of attacks of stenocardia;
disturbances of a heart rhythm (supraventricular takikhardiya, ventricular premature ventricular contraction);
hyperthyroidism (complex therapy);
prevention of attacks of migraine.
Egilok Retard
chronic heart failure in compensation stage: the patient receiving standard therapy by diuretics, APF inhibitors and cardiac glycosides;
hyperkinetic cardial syndrome, tachycardia.

Route of administration and doses:

Egilok
Inside, with food or right after food, tablets can be halved, but not to chew and wash down with liquid.
Arterial hypertension: the initial daily dose makes 50–100 mg in 1–2 receptions (in the morning and in the evening). At insufficient therapeutic effect the daily dose can be gradually raised to 100–200 mg.
Stenocardia, arrhythmias, prevention of attacks of migraine: 100–200 mg a day in 2 receptions (in the morning and in the evening).
Secondary prevention of a myocardial infarction: 200 mg a day in 2 receptions (in the morning and in the evening).
The functional disturbances of cordial activity which are followed by tachycardia: 100 mg a day in 2 receptions (in the morning and in the evening).
At elderly patients, at renal failures, and also in need of carrying out a hemodialysis the dose is not changed.
At abnormal liver functions the dose of drug should be lowered depending on a clinical state.
Egilok Retard
Inside, in the morning, during food or on an empty stomach, without chewing, washing down with liquid. Tablets, coated it is possible to break in half. According to any indications drug is appointed once a day. For the purpose of the prevention of bradycardia the dose is selected individually and increased gradually. The maximum daily dose — 200 mg.
Arterial hypertension: an initial dose — 50 mg once a day. If this quantity is not enough, strengthening of hypotensive effect can be received, having increased a dose to 100–200 mg a day or having appointed in addition other antihypertensive.
Stenocardia: an initial dose — 50 mg once a day. Strengthening of anti-anginal effect can be received, increasing a dose to 100–200 mg a day or additional purpose of other anti-anginal means.
Prevention of a myocardial infarction, maintenance therapy: a usual maintenance dose — 200 mg a day.
Heart failure with clinical symptoms: an initial dose — 25 mg a day. In 2 weeks it is possible to increase a day dose to 50 mg, in 2 weeks — to 100 mg, and later 2 more weeks — to 200 mg.
Disturbances of a heart rhythm: a usual dose — 50–200 mg once a day.
Hyperkinetic cardial syndrome, tachycardia: a usual dose — 50–200 mg once a day.
Prevention of attacks of migraine: 100–200 mg once a day.
At elderly patients, at renal failures, and also in need of carrying out a hemodialysis the dose is not changed.
At abnormal liver functions the dose of drug should be selected individually depending on a clinical state.

Features of use:

Monitoring of the patients accepting beta adrenoblockers includes regular observation of ChSS and the ABP, content of glucose in blood at patients with a diabetes mellitus. If necessary, for patients with diabetes, the dose of insulin or the antidiabetic means appointed inside should be picked up individually. It is necessary to train the patient in a technique of calculation of ChSS and to instruct about need of medical consultation at ChSS <50 уд. / min. At reception of a dose higher than 200 mg a day decrease cardioselectivity.
At heart failure treatment metoprololy is begun only after achievement of a stage of compensation.
Strengthening of expressiveness of reactions of hypersensitivity (against the background of the burdened allergological anamnesis) and lack of effect of introduction of usual doses of Epinephrinum (adrenaline) is possible.
Can strengthen symptoms of disturbance of peripheric arterial circulation.
Drug withdrawal is carried out gradually, reducing a dose within 10 days. At the sharp termination of treatment there can be a withdrawal (strengthening of attacks of stenocardia, increase in the ABP). Special attention at drug withdrawal needs to be paid to patients with stenocardia.
At an angina of exertion the picked-up dose of drug has to provide heart rate at rest within 55–60 уд. / mines, at loading — no more than 110 уд. / min.
Metoprolol can mask some clinical manifestations of a hyperthyroidism (for example tachycardia). Sharp cancellation at patients with a thyrotoxicosis is contraindicated: strengthening of symptomatology is possible.
At a diabetes mellitus can mask the tachycardia caused by a hypoglycemia. Unlike non-selective beta adrenoblockers practically does not strengthen the hypoglycemia caused by insulin and recovery of concentration of glucose in blood to normal level does not detain.
In need of appointment to patients with bronchial asthma as the accompanying therapy use beta2-adrenostimulyator, with a pheochromocytoma — alpha adrenoblockers.
In need of carrying out surgical intervention it is necessary to warn the anesthesiologist about the carried-out therapy (means for the general anesthesia with the minimum negative inotropic effect are chosen), drug withdrawal is not required.
The drugs reducing stocks of catecholamines (for example Reserpinum), can strengthen effect of beta adrenoblockers therefore the patients accepting such combinations of drugs have to be under constant observation of the doctor regarding identification of excessive decrease in the ABP or bradycardia.
At elderly patients — it is recommended to exercise control of function of a liver regularly. Correction of the mode of dosing is required only in case of emergence in patients of advanced age of the accruing bradycardia (<50 уд. / mines), the expressed decrease in the ABP (the GARDEN <100 mm of mercury.), AV of blockade, a bronchospasm, ventricular arrhythmias, heavy abnormal liver functions, sometimes it is necessary to stop treatment.
It is necessary to carry out special control of a condition of patients with the depressive frustration accepting метопролол; in case of development of the depression caused by reception of beta adrenoblockers it is recommended to stop therapy.
Due to the lack of enough clinical data drug is not recommended to be used at children.
The patients using contact lenses have to consider that against the background of treatment by beta adrenoblockers reduction of products of the lacrimal liquid is possible.
Influence on ability to manage vehicles and a difficult technique
In an initiation of treatment metoprololy patients can test dizziness, fatigue. In this case they have to refrain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions. Further definition of a safe dose is carried out individually.

Side effects:

Side effects depend on individual sensitivity of the patient. Usually they insignificant also disappear after drug withdrawal.
From a nervous system: increased fatigue, weakness, headache, delay of speed of mental and motor reactions; seldom — paresthesias in extremities (at patients with the "alternating" lameness and Reynaud's syndrome), a depression, concern, decrease in attention, drowsiness, sleeplessness, dreadful dreams, confusion of consciousness or short-term disturbance of memory, an asthenic syndrome, muscular weakness.
From sense bodys: seldom — decrease in visual acuity, decrease in secretion of the lacrimal liquid, dryness and morbidity of eyes, conjunctivitis, a sonitus.
From cardiovascular system: sinus bradycardia, heartbeat, decrease in the ABP, orthostatic hypotension (dizziness, sometimes loss of consciousness). Seldom — decrease in contractility of a myocardium, temporary aggravation of symptoms of chronic heart failure (hypostases, puffiness of feet and/or the lower part of shins, an asthma), arrhythmias, manifestation of a vasomotor spasm (strengthening of disturbance of peripheric circulation, a cold snap of the lower extremities, Reynaud's syndrome), disturbance of conductivity of a myocardium, in isolated cases — AV blockade, a cardialgia.
From the alimentary system: nausea, vomiting, an abdominal pain, dryness in a mouth, diarrhea, a lock, taste change.
From integuments: urticaria, skin itch, rash, exacerbation of psoriasis, psoriazopodobny skin reactions, dermahemia, dieback, photodermatosis, sweating strengthening, reversible alopecia.
From respiratory system: a nose congestion, difficulty of an exhalation (a bronchospasm at appointment in high doses — owing to loss of selectivity and/or at predisposed patients), an asthma.
From endocrine system: a hypoglycemia (at the patients receiving insulin), it is rare — a hyperglycemia (at patients with an insulin-dependent diabetes mellitus).
Laboratory indicators: seldom — thrombocytopenia (unusual bleedings and hemorrhages), an agranulocytosis, a leukopenia, increase in activity of "hepatic" enzymes; extremely seldom — a hyperbilirubinemia.
Influence on a fruit: the pre-natal growth inhibition, a hypoglycemia, bradycardia is possible.
Others: the dorsodynia or joints, as well as all beta adrenoblockers, in isolated cases can cause insignificant increase in body weight, decrease in a libido and/or potentiality.

Interaction with other medicines:

Simultaneous use with MAO inhibitors owing to considerable strengthening of hypotensive action is not recommended. Having rummaged in treatment between reception of MAO inhibitors and a metoprolola has to make not less than 14 days.
Simultaneous in/in administration of verapamil can provoke a cardiac standstill.
Co-administration of nifedipine leads to considerable decrease in the ABP.
Means for an inhalation anesthesia (derivatives of hydrocarbons) increase risk of oppression of function of a myocardium and development of arterial hypotension.
Beta адреностимуляторы, theophylline, cocaine, estrogen (a sodium delay), indometacin and other NPVS (a delay of sodium and blocking of synthesis of prostaglandins kidneys) weaken hypotensive effect.
Mutual strengthening of the oppressing action on TsNS — with ethanol is noted; summation of cardiodepressive effect — with narcotic means; increase in risk of disturbances of peripheric circulation — with ergot alkaloids.
At joint reception with peroral hypoglycemic drugs decrease in their effect is possible; with insulin — increase in risk of development of a hypoglycemia, strengthening of its expressiveness and duration, masking of some symptoms of a hypoglycemia (tachycardia, perspiration, increase in the ABP).
At a combination to antihypertensives, nitroglycerine, alcohol or BKK sharp decrease in the ABP can develop (extra care is necessary at a combination to Prazozinum); increase in expressiveness of an urezheniye of ChSS and oppression of AV of conductivity — at use of a metoprolol with verapamil, diltiazem, antiarrhytmic means (Amiodaronum), Reserpinum, alpha метилдопой, a clonidine, guanfatsiny, means for the general anesthesia and cardiac glycosides. If метопролол and the clonidine is accepted at the same time, at cancellation of a metoprolol the clonidine is cancelled in several days (in connection with risk of emergence of a withdrawal).
Inductors of microsomal enzymes of a liver (rifampicin, barbiturates) lead to strengthening of metabolism of a metoprolol, to decrease in its concentration in a blood plasma and to reduction of effect. Inhibitors (Cimetidinum, oral contraceptives, fenotiazina) — increase concentration in plasma.
The allergens used for an immunotherapy or extracts of allergens for skin tests at combined use with metoprololy, increase risk of emergence of system allergic reactions or an anaphylaxis.
Iodinated radiopaque substances for in/in introductions increase risk of development of anaphylactic reactions.
Reduces clearance of lidocaine, increases concentration of lidocaine in plasma.
Reduces clearance of xanthines (except Diphyllinum), especially at patients with initially increased clearance of theophylline under the influence of smoking.
 Strengthens and prolongs action of the anti-depolarizing muscle relaxants; extends anti-coagulative effect of coumarins.
At combined use with ethanol the risk of the expressed decrease in the ABP increases.
The concomitant use of food does not influence action of a metoprolol.

Contraindications:

hypersensitivity to a metoprolol or to other ingredients of drug;
cardiogenic shock;
AV blockade of II and III degrees;
sinuatrial blockade;
syndrome of weakness of a sinus node;
the expressed bradycardia (ChSS <50 уд. / mines);
heart failure in a decompensation stage;
Printsmetal's stenocardia;
arterial hypotension (in case of use at secondary prevention of a myocardial infarction — the GARDEN <100 mm of mercury.);
lactation period;
concomitant use of MAO inhibitors or simultaneous in/in administration of verapamil.

With care (see also "Special instructions"):
diabetes mellitus;
metabolic acidosis;
bronchial asthma;
chronic obstructive pulmonary diseases (emphysema of lungs, chronic obstructive bronchitis);
obliterating diseases of peripheral vessels (the "alternating" lameness, Reynaud's syndrome);
chronic liver and/or renal failure,
myasthenia;
pheochromocytoma;
AV blockade of the I degree;
thyrotoxicosis;
depression (including in the anamnesis);
psoriasis;
pregnancy;
children's age up to 18 years (efficiency and safety are not defined);
advanced age.

Use at pregnancy and feeding by a breast

During pregnancy appoint according to strict indications taking into account a ratio advantage/risk (in connection with possible development in a fruit of bradycardia, arterial hypotension, a hypoglycemia). At the same time make careful observation, especially behind fetation. Strict observation of newborns during 48–72 h after delivery is necessary.
Influence of a metoprolol on the newborn when feeding by a breast is not studied therefore the women accepting Egilok and Egilok Retard should stop feeding by a breast.

Overdose:

The first signs of overdose are shown in 20 min.-2 the h after administration of drug.
Symptoms: the expressed heavy sinus bradycardia, dizziness, nausea, vomiting, cyanosis, decrease in the ABP, arrhythmia, ventricular premature ventricular contraction, a bronchospasm, a syncope, at acute overdose – cardiogenic shock, a loss of consciousness, a coma, AV blockade (up to development of total cross block and a cardiac standstill), a cardialgia.
Treatment: a gastric lavage and purpose of the adsorbing means; symptomatic therapy: at the expressed decrease in the ABP in the patient has to be in the provision of Trendelenburga; in case of excessive decrease in the ABP, bradycardia and heart failure — in/in at an interval of 2–5 min. introduction beta адреностимуляторов (before achievement of desirable effect) or in/in 0,5–2 mg of Atropini sulfas.
In the absence of positive effect — a dopamine, Dobutaminum or Norepinephrinum (noradrenaline).
As the subsequent measures purpose of 1-10 mg of a glucagon, statement of a trasvenozny intrakardialny electrostimulator is possible.
At a bronchospasm it is necessary to enter into stimulators of beta2-adrenoceptors.
At spasms — slow in/in administration of diazepam.
Metoprolol is badly brought by means of a hemodialysis.

Storage conditions:

Period of validity 3 years. List B.: At a temperature not above 30 °C.

Issue conditions:

According to the recipe