Egilok of the tab. of 50 mg No. 60

Pharmacological properties

Pharmacodynamics. metoprolol — a cardioselective blocker β1-адренорецепторов. has no membrane stabilizing effect and has no internal sympathomimetic activity.

It suppresses effects of the enhanced sympathetic activity in heart, substantially reduces ChSS, sokratitelny activity of heart, warm emission and the ABP.

Pri AG metoprolol lowers the arterial blood pressure at patients both in a standing position, and in a prone position. The long antihypertensive effect of medicament connected with gradual reduction of OPSS.

long use of medicament leads

At patients with AG to significant degrowth of a left ventricle and improvement of diastolic function of a left ventricle.

At men from easy and moderate AG metoprolol reduces mortality caused by cardiovascular diseases (first of all the frequency of cases of sudden death, myocardial infarctions with a lethal outcome and strokes).

Thanks to decrease in the system ABP, decrease in ChSS and sokratitelny activity of heart metoprolol is reduced by the need of a myocardium for oxygen. Reducing ChSS, and thus extending diastole duration, metoprolol improves perfusion and oxygenation of sites of a myocardium with the broken blood supply.

Besides, medicament reduces quantity, duration and weight of attacks of stenocardia and also asymptomatic ischemia and increases shipping of physical activities.

Pri a myocardial infarction metoprolol is reduced by mortality by reduction of risk of sudden death. This effect first of all is connected with prevention of cases of fibrillation of ventricles. Decline in mortality is noted irrespective of whether applied metoprolol on early or at a late stage of a disease and also in cases of the increased risk and at patients with diabetes.

Pri use of a metoprolol after a myocardial infarction the risk of developing of a repeated heart attack decreases.

Pri of stagnant heart failure, arisen because of a dilatatsionny cardiomyopathy, metoprolol, appointed at first in a low dose (2 times on 5 mg/days) which was gradually raised then, improved cardiac performance, quality of life and physical activity of patients; reduced the number of repeated hospitalization owing to heart failure and the need for transplantation of heart.

Pri of supraventricular tachycardia, fibrillation of auricles and ventrikulyarny premature ventricular contraction metoprolol reduces the ventrikulyarny frequency and the number of ekstraventrikulyarny reductions.

peripheral sosudo- and the bronkhosuzhivayushchy effect of a metoprolol is less significant

In therapeutic doses, than at non-selective blockers of β-adrenoceptors.

Compared with non-selective blockers of β-adrenoceptors, metoprolol in much smaller degree influences synthesis of insulin and metabolism of carbohydrates. It only in insignificant degree changes cardiovascular reaction to a hypoglycemia or increases hypoglycemia duration.

In short clinical trials metoprolol induced slight increase of level of triglycerides and insignificant decrease in level of free fatty acids in blood plasma. Also insignificant decrease in the LPVP level XC was in certain cases observed, however it was smaller, than at use of non-selective blockers of β-adrenoceptors. However in long clinical trial the significant decrease in level of the general in XC in blood plasma in several years of treatment metoprololy is shown.

Pharmacokinetics

Metoprolol quickly and almost is completely soaked up by

in a GIT. Pharmacokinetic parameters of a metoprolol linear in the range of therapeutic doses.

C _max in blood plasma is reached in 1.5-2 h after reception. After absorption metoprolol it is metabolized at the first passing through a liver. The bioavailability of a metoprolol is nearly 50% after one-time reception and nearly 70% — after repeated use.

Concomitant use of food can increase bioavailability of a metoprolol by 30–40%.

Linking with proteins of blood plasma low — about 5-10%.

Metoprolol is widely distributed by

in fabrics and has the high volume of distribution (5.6 l/kg of body weight).

Metoprolol is metabolized by

in a liver by means of P450 cytochrome enzymes. Metabolites have no pharmacological activity.

T _½ — 3.5 h on average (it varies within 1–9 h).

General clearance — about 1 l/min.

More than 95% of the accepted dose are removed by

with urine, 5% — are removed in not changed look. In certain cases the last size can increase to 30%.

At patients of advanced age the pharmacokinetic parameters of a metoprolol essentially do not change.

Renal failure does not affect system bioavailability and elimination of a metoprolol. However in such cases the excretion of metabolites decreases. Considerable accumulation of metabolites was observed at patients with a renal failure (level of glomerular filtration — 5 ml/min.). However accumulation of metabolites does not raise extent of β-blockade.

Liver failure slightly influences pharmacokinetic parameters of a metoprolol. However in heavy cirrhosis and after operation on a porto-caval anastomosis the bioavailability of a metoprolol can increase, and the general clearance to decrease. At patients after operation on a porto-caval anastomosis the general clearance decreased approximately up to 0.3 l/min, and AUC increased approximately by 6 times compared with healthy faces.

Indication

Ag as monotherapy or in a combination with other antihypertensive drugs; for decline in mortality owing to cardiovascular diseases or diseases of a coronary artery at patients with ag.

Stenocardia. Drug can be used as monotherapy or in a combination with other anti-anginal means.

for the purpose of decline in mortality and the frequency of a repeated myocardial infarction (as secondary prevention).

Disturbance of a heart rhythm (sinus tachycardia, supraventricular tachycardia, ventricular premature ventricular contraction).

Functional disturbances of warm activity which are followed by tachycardia.

Prevention of migraine.

Use

Egilok. a pill is taken irrespective of meal. in need of a tablet it is possible to divide.

Dose should be established to

individually, gradually raising it in order to avoid excessive bradycardia.

AG: at easy and moderate AG the initial dose makes 25 mg or 50 mg 2 times a day (in the morning and in the evening). If necessary the daily dose can be raised gradually to 100 mg 2 times a day or to apply other antihypertensive medicaments in a combination with Egilok.

Stenocardia: the initial dose of medicament of 25 mg or 50 mg 2–3 times a day which if necessary can be raised gradually to 200 mg/days or to combine medicament with other anti-anginal means.

Supported therapy after a myocardial infarction: a usual dose — 50–100 mg 2 times a day (in the morning and in the evening).

Arrhythmia: an initial dose — 25–50 mg 2 or 3 times a day. If necessary the daily dose can be raised gradually to 200 mg or to apply other antiarrhytmic means in a combination with Egilok.

Functional disturbances of warm activity which are followed by tachycardia: the usual daily dose makes 50 mg 2 times a day (in the morning and in the evening) which if necessary can be raised to 100 mg 2 times a day.

Prevention of migraine: the usual daily dose makes 50 mg 2 times a day (in the morning and in the evening) which if necessary can be raised to 100 mg 2 times day.

Special groups of patients

Patients with a renal failure do not need dose adjustment.

does not have

need to change a dose to patients with cirrhosis as linking of a metoprolol with proteins of plasma low (5–10%). In a heavy liver failure (for example after shunting) there can be necessary a dose decline of a metoprolol.

Patients of advanced age do not need a dose decline.

Egilok Retard. At all indications it is necessary to take the medicament 1 time a day.

Daily dose is recommended to be accepted in the morning with a small amount of water, without chewing a tablet. A pill can be taken irrespective of meal or at meal time.

If necessary a tablet, coated, it is possible to break in half.

in order to avoid bradycardia a dose needs to be selected individually.

AG: the average daily dose makes 50 mg in 1 reception. If necessary the dose can be raised to 100–200 mg in 1 reception. Egilok Retard it is possible to apply to strengthening of hypotensive effect with other antihypertensives.

Stenocardia: the dose of medicament makes 50 mg/days in 1 reception. If necessary the dose can be raised to 100–200 mg in 1 reception. Egilok Retard it is possible to apply to strengthening of clinical effect with other anti-anginal drugs.

After a myocardial infarction the maintenance dose makes 200 mg of 1 times a day.

Stable chronic heart failure: the recommended initial dose of medicament for the first 2 weeks makes 25 mg/days. After 2 weeks the dose can be raised to 50 mg of 1 times a day and further each 2 weeks can double up to 100 mg, then — up to 200 mg. Gradual increase in a dose at administration of medicaments of a metoprolol of the immediate mechanism of action before achievement of a daily dose of 25 mg is recommended. At hard cases of heart failure it is recommended to apply low doses or tablets of a metoprolol of not prolonged action.

In arrhythmia the initial dose of medicament makes 50–200 mg of 1 times a day.

At functional disturbances of heart the usual dose of medicament makes 50–200 mg of 1 times a day.

For prevention of attacks of migraine — 100–200 mg/days in 1 reception.

Contraindication

Hypersensitivity to a metoprolol or any other component of medicament or to other blockers of β-adrenoceptors, av-blockade іі and ііі degrees, the profound sinus bradycardia, a syndrome of weakness of a sinus node, cardiogenic shock, the significant disturbances of peripheric circulation, dekompensirovanny heart failure, an acute myocardial infarction, if chss 45/mines, p–q interval — 240 ms, systolic hell — 100 mm Hg., the patients needing long and continuous treatment by inotropic β-agonists.

Side effects

from central nervous system: very often — increased fatigue; often — dizziness, a headache; infrequently — paresthesias, muscular spasms, a depression, disturbance of attention, drowsiness, insomnia, dreadful dreams; seldom — nervousness, tension, sexual disturbances; very seldom — amnesia, memory disturbance, confusion of consciousness, hallucinations.

from a cardiovascular system: often — bradycardia, postural hypotension (it is very rare with a loss of consciousness), cold extremities, tachycardia; infrequently — aggravation of symptoms of heart failure, AV blockade of the I degree, hypostasis, pain in heart; seldom — arrhythmias, disturbance of conductivity; very seldom — the gangrene caused by earlier existing disturbance of peripheric circulation.

from a GIT: often — nausea, abdominal pain, diarrhea, a constipation; infrequently — vomiting; seldom — dryness in a mouth, change of indicators of function of a liver; very seldom — hepatitis.

from integuments: infrequently — rash (small tortoiseshell, psoriazopodobny and dystrophic damages of skin), the strengthened sweating; seldom — an alopecia; very seldom — a photosensitization, progressing of psoriasis.

from a respiratory system: often — an asthma at physical activity; infrequently — a bronchospasm (even in the absence of an obstructive disease of lungs); seldom — rhinitis.

Sensor system: seldom — a disorder of vision, a xerophthalmia and/or irritation of eyes, conjunctivitis; very seldom — a ring in ears, disturbance of taste.

Metabolic disturbances: infrequently — increase in body weight.

from the system of blood: very seldom — thrombocytopenia.

from the musculoskeletal system: very seldom — an arthralgia.

Special instructions

Acute anaphylaxis can hard proceed at the patients accepting metoprolol.

Metoprolol can strengthen the existing bradycardia.

Metoprolol can strengthen symptoms of disturbance of peripheric circulation.

needs to avoid the sharp termination of administration of drug. Egilok cancel gradually by step decrease in doses for 7–10 days.

Sharp medicament withdrawal can strengthen symptoms of stenocardia and lead to development of a myocardial infarction. Patients with coronary artery disease need special attention during medicament withdrawal.

Heart failure has to be compensated to

prior to reception of a metoprolol, and the condition of compensation should be supported throughout the entire period of treatment.

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In spite of the fact that cardioselective blockers of β-adrenoceptors influence respiratory function, than non-selective blockers of β-adrenoceptors less, it is whenever possible recommended not to appoint them to patients with HOBL. In need of purpose of a metoprolol the patient with simultaneous introduction β OH can be necessary for ₂ - agonists (tablets or spray) or change of a dose of _{2 which are earlier applied β} - agonists.

When prescribing medicament sick diabetes needs to control constantly carbohydrate metabolism and if necessary to korrigirovat a dose of insulin and oral antidiabetic drugs.

At patients with a pheochromocytoma metoprolol needs to be combined with blockers of α-adrenoceptors.

Bioavailability of a metoprolol can increase in cirrhosis.

At the patients receiving blockers of β-adrenoceptors, adrenaline can raise the ABP and cause (reflex) bradycardia; this reaction is less possible at use of selection blockers of β-adrenoceptors.

anesthesiologist has to be warned by

Before any surgery that the patient accepts metoprolol.

As before surgery Egilok needs to be cancelled, cancellation needs to be carried out not later than 48 h before operation, except for special cases, for example a thyrotoxicosis or a pheochromocytoma.

In certain cases introductions of blockers of β-adrenoceptors before operation can be

useful as they can reduce aritmogenny effects and coronary circulation in a surgical stress which causes advantage of a sympathetic tone. In case of use of a blocker of β-adrenoceptors it is necessary to choose anesthetic with weak negative inotropic effect to reduce risk of oppression of a myocardium.

earlier existing moderate disturbances of peredserdno-ventricular conductivity, sometimes — with development of peredserdno-ventricular blockade Very seldom can amplify.

This medicament patients cannot appoint

with hereditary intolerance of fructose, glucose galactose absorption disturbance and also with insufficiency of invertase/isomaltase.

Use during pregnancy and feeding by a breast. Due to the lack of these controlled clinical trials during pregnancy and feeding by a breast Egilok it is possible to apply only when the advantage of use of medicament for mother justifies possible risk for the fruit/child.

Whenever possible use of a metoprolol is stopped for 48–72 h till the expected period of childbirth. If administration of medicament is inevitable, for babies the constant observation for several days (48–72 h) after the birth as medicament can get to a blood stream of a fruit is necessary and cause bradycardia, respiratory depression, decrease in the ABP and a hypoglycemia.

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Despite ability of a metoprolol to get through a placental barrier, did not reveal signs of its fetotoksichnost. In spite of the fact that at introduction of a metoprolol in therapeutic doses only the insignificant amount of medicament gets into breast milk and has no significant β-blocking effect on children of chest age, behind them it is necessary to establish constant control (bradycardia is possible).

Children. Experience of use of medicament for children is absent.

Ability to influence speed of response at control of vehicles or work with other mechanisms. As at administration of medicament Egilok there can be dizziness and weakness, for treatment it is necessary to refrain from control of vehicles and work with difficult mechanisms.

Antihypertensive effect of medicament the egilok and other antihypertensive drugs, as a rule, is summarized by

Interaction

. in order to avoid hypotension the constant observation of patients who receive combinations of such means is necessary. however summation of effects of antihypertensive medicaments can use if necessary for achievement of effective control hell.

Drug cannot be combined with such medicines:

• verapamil (in/in entered) or other similar blockers of calcium channels (risk of an asystolia);
• MAO inhibitors.

needs to be careful at a combination with such means:

• oral antiarrhythmic means, blockers of calcium channels of type of verapamil and diltiazem, parasympathomimetics (risk of developing hypotension, bradycardia and AV blockade);
• foxglove glycosides (risk of developing bradycardia, disturbance of conductivity; metoprolol does not affect positive inotropic effect of medicaments of a foxglove);
• nitrates and other antihypertensive medicaments (especially groups of a guanetidin, reserpine, Methyldopa, a clonidine and a guanfatsin) because of risk of hypotension and/or bradycardia;
• some medicaments operating on central nervous system, for example: hypnotic drugs, tranquilizers, three - and tetracyclic antidepressants, neuroleptics and alcohol (risk of developing hypotension);
• medicaments (risk of oppression of warm activity);
• α- and β-sympathomimetics (risk of hypertensia, heavy bradycardia; possibility of cardiac arrest);
• at a concomitant use with a clonidine treatment needs to be stopped, it is obligatory at first canceling metoprolol, and then (in several days) — a clonidine. If at first to cancel a clonidine, hypertensive crisis is possible;
• ergotamine (strengthening of vasopressor effect);

β ₂ - sympathomimetics (functional antagonism);

• NPVP (for example indometacin) because of possible decrease in antihypertensive effect;
are oestrogenic
• (possible decrease in antihypertensive effect of a metoprolol);
• oral antidiabetic medicaments and insulin (metoprolol can enhance their hypoglycemic effect and disguise hypoglycemia symptoms);
• kurarepodobny muscle relaxants (strengthening of neuromuscular blockade);
• inhibitors of enzymes (for example Cimetidinum) — possible strengthening of effects of a metoprolol owing to increase in its concentration in blood plasma;
• inductors of enzymes (rifampicin and barbiturates) — effects of a metoprolol can decrease owing to increase in hepatic metabolism.

Simultaneous use of the means blocking nice a ganglion, other β-blockers (for example eye drops) needs constant observation.

Concomitant use of food considerably does not influence medicament pharmacokinetics.

Overdose

Symptoms: arterial hypotension, sinus bradycardia, av-blockade, heart failure, cardiogenic shock, an asystolia, nausea, vomiting, cyanosis, a bronchospasm, a hypoglycemia, a loss of consciousness, a coma, in certain cases — a hypoglycemia.

Treatment: gastric lavage, intake of activated carbon, in heavy hypotension — agonists of β-adrenoceptors (Norepinephrinum) or in/in administration of atropine (in bradycardia). In the absence of effect it is necessary to appoint dopamine, Dobutaminum, Norepinephrinum (noradrenaline). There can be effective a glucagon (1–10 mg). In hard cases the implantation of an artificial pacemaker can be necessary. A bronchospasm eliminate with introduction in/in β ₂ - adrenomimetik (for example terbutalin). Metoprolol is practically not brought from an organism by means of a hemodialysis.

Storage conditions

At a temperature of 30 °C.