Метокард®

General characteristics. Structure:

Active ingredient: 50 mg or 100 mg of a metoprolol of tartrate in 1 tablet.

Excipients: lactose, povidone, talc, magnesium stearate, cellulose microcrystallic, starch rice.

Pharmacological properties:

Pharmacodynamics. Metokard treats cardioselective blockers β — the adrenoceptors which do not have internal sympathomimetic activity and membrane stabilizing properties. Possesses hypotensive, anti-anginal and antiarrhytmic action.

Blocking in low doses _β1 — heart adrenoceptors, reduces stimulated catecholamines formation of tsAMF from ATP, reduces intracellular current ^{of Sa2+}, renders negative hrono-, dromo-, batmo-and inotropic action (urezhat heart rate, conductivity and excitability oppresses, reduces contractility of a myocardium).

The general peripheric resistance at the beginning of use β — adrenoblockers (in the first 24 hours after oral administration) — increases (as a result of reciprocal increase of activity of α-adrenoceptors and elimination of stimulation _{β2–адренорецепторов}) which in 1-3 days is returned to initial, and at long appointment — decreases.

Acute anti-hypotensive action is caused by reduction of cordial emission, the stable anti-hypertensive effect develops within 2-3 weeks and the system renin-angiotenzivnoy (is of great importance at patients with initial hypersecretion of a renin) and the central nervous system, recovery of sensitivity of baroreceptors of an aortic arch (there is no strengthening of their activity in response to a lowering of arterial pressure) and, as a result, reduction of peripheral sympathetic influences is caused by decrease in synthesis of a renin, and accumulation of a renin of plasma, activity oppression. Reduces the increased arterial pressure at rest, at a physical tension and a stress.

The Antiangialny effect is defined by decrease in need of a myocardium for oxygen as a result of reduction of heart rate (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.

Arterial pressure decreases in 15 minutes, as much as possible — in 2 hours and decrease proceeds within 6 hours, diastolic arterial pressure 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 atrioventricular 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 heart rate, or can even lead to recovery of a sinoatrial rate. Prevents development of migraine.

At use in average therapeutic doses, unlike non-selective beta adrenoblockers, exerts less expressed impact on the bodies containing _{β2–адренорецепторы} (a pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchial tubes and a uterus) and on carbohydrate metabolism. At use in high doses (more than 100 mg/days) renders the blocking effect on both subtypes of β-adrenoceptors..........

Pharmacokinetics. Metoprolol quickly and almost completely (95%) is soaked up in digestive tract. The maximum concentration in a blood plasma is reached in 1-2 hours after intake. The elimination half-life averages 3,5 h (ranging from 1 h to 9 h).

Bioavailability makes 50% at the first reception and increases up to 70% at repeated use. Meal increases bioavailability for 20 – 40%. Bioavailability of a metoprolol increases at cirrhosis.

Communication with proteins of plasma on average 10%. Drug gets through hematoencephalic and placental barriers. 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 an invariable 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 insufficiency of function of a liver, the dose of drug has to be lowered. Is not removed at a hemodialysis.

Indications to use:

• arterial hypertension (as monotherapy or in a combination with other anti-hypertensive drugs), including hyperkinetic type, tachycardia;
• coronary heart disease: a myocardial infarction (secondary prevention - complex therapy), prevention of attacks of stenocardia;
• disturbances of a heart rhythm (supraventricular tachycardia, ventricular premature ventricular contraction);
• hyperthyroidism (complex therapy);
• prevention of attacks of migraine.

Route of administration and doses:

Pill is taken inside along with acceptance of 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 and/or additional purpose of other anti-hypertensive means. Maximum daily dose of 200 mg.

Stenocardia, arrhythmias, prevention of attacks of migraine. 100 - 200 mg a day in two steps (in the morning and in the evening).

Secondary prevention of a myocardial infarction. 200 mg a day in two steps (in the morning and in the evening).

The functional disturbances of cordial activity which are followed by tachycardia. 100 mg a day in two steps (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.

Features of use:

Control of the patients accepting beta adrenoblockers includes regular heart-rate monitoring (ChSS) and the arterial pressure, content of glucose of blood at patients with a diabetes mellitus. If necessary, for patients with a diabetes mellitus, the dose of insulin or the hypoglycemic 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 less than 50 beats/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 hypersensitivity reactions (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 syndrome of "cancellation" (strengthening of attacks of stenocardia, increase in arterial pressure).

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 beats/min, at loading — no more than 110 beats/min.

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.

Metoprolol can mask some clinical manifestations of a hyperthyroidism (for example, tachycardia). Sharp cancellation at patients with a thyrotoxicosis is contraindicated as it is capable to strengthen symptomatology.

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 of blood to normal level does not detain.

In need of appointment to patients with bronchial asthma, as the accompanying therapy use beta 2 - адреностимуляторы; at a pheochromocytoma — alpha adrenoblockers.

In need of carrying out surgical intervention it is necessary to warn the anesthesiologist about the carried-out therapy (the choice of means for the general anesthesia with the minimum negative inotropic effect), drug withdrawal is not recommended.

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 detection of an excessive lowering of arterial pressure and 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 sick advanced age of the accruing bradycardia (less than 50 beats/min), the expressed decrease in the ABP (systolic arterial pressure is lower than 100 mm of mercury.), an atrioventricular block, a bronchospasm, ventricular arrhythmias, heavy abnormal liver functions, sometimes it is necessary to stop treatment.

Patients with a heavy renal failure are recommended to exercise control of function of kidneys. 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.

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 safety of a dose is carried out individually.

Pregnancy and period of a lactation. During pregnancy appoint taking into account a ratio advantage/risk (in connection with 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 METOKARD should stop feeding by a breast.

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, muscular weakness.

From sense bodys: seldom — decrease in sight, decrease in secretion of the lacrimal liquid, dryness and morbidity of eyes, conjunctivitis, a sonitus.

From cardiovascular system: sinus bradycardia, heartbeat, lowering of arterial pressure, 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.

From the alimentary system: nausea, vomiting, an abdominal pain, dryness in a mouth, diarrhea, a lock, taste change, an abnormal liver function.

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 — loss of selectivity and/or at predisposed patients), an asthma.

From endocrine system: a hyperglycemia at patients with a non-insulin-dependent diabetes mellitus, a hypothyroidism.

Laboratory indicators: seldom — thrombocytopenia (unusual bleedings and hemorrhages), an agranulocytosis, a leukopenia, increase in activity of "liver enzymes", it is extremely rare — 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-blockers 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 a considerable lowering of arterial pressure.

Means for inhalation general anesthesia (derivatives of hydrocarbons) increase risk of oppression of function of a myocardium and development of arterial hypotension.

Beta адреностимуляторы, theophylline, cocaine, etrogena (a sodium delay), indometacin and other nonsteroid protivospalitelny drugs (a delay of sodium and blocking of synthesis of prostaglandin kidneys) weaken hypotensive effect.

Strengthening of the oppressing action on the central nervous system — with ethanol is noted; summation of cardiodepressive effect — with means for the general anesthesia; increase in risk of disturbances of peripheric circulation — with ergot alkaloids.

At joint reception with hypoglycemic means for intake decrease in their effect is possible; with insulin — increase in risk of development of a hypoglycemia, strengthening of its expressiveness and lengthening, masking of some symptoms of a hypoglycemia (tachycardia, perspiration, increase in arterial pressure).

At a combination to antihypertensives, diuretics, nitroglycerine or blockers of slow calcium channels the sharp lowering of arterial pressure can develop (extra care is necessary at a combination to Prazozinum); increase in expressiveness of an urezheniye of heart rate and oppression of atrioventricular 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, then at cancellation of a metoprolol the clonidine is cancelled in several days (in connection with risk of emergence of a syndrome of "cancellation").

Inductors of microsomal enzymes of a liver (rifampicin, barbiturates) lead to strengthening of metabolism of a metoprolol, to decrease in concentration of a metoprolol 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 xanthine (except Diphyllinum), especially with initially increased clearance of theophylline under the influence of smoking. Reduces clearance of lidocaine, increases concentration of lidocaine in a blood plasma.

Strengthens and prolongs action of the anti-depolarizing muscle relaxants; extends anticoagulating effect of coumarins.

At combined use with ethanol the risk of the expressed decrease in the ABP increases. Rub - and tetracyclic antidepressants, antipsychotic HP (neuroleptics), sedative and HP hypnotic drugs strengthen oppression of TsNS.

Contraindications:

• hypersensitivity to a metoprolol or other components of drug, other beta-blockers;
• cardiogenic shock;
• atrioventricular (AV) blockade of the II-III degree;
• sinuatrial (SA) blockade;
• sick sinus syndrome;
• the expressed bradycardia;
• heart failure in a decompensation stage;
• Printsmetal's stenocardia;
• arterial hypotension (in case of use at secondary prevention of a myocardial infarction – systolic the ABP less than 100 mm hg, ChSS less than 45 уд. / mines;
• the lactation period (see. "Pregnancy and period of a lactation");
• concomitant use of MAO inhibitors or simultaneous intravenous administration of verapamil (see. "Interaction with other medicines");
• age up to 18 years (efficiency and safety are not established).

With care — a diabetes mellitus, a metabolic acidosis, bronchial asthma, a chronic obstructive pulmonary disease (emphysema of lungs, chronic obstructive bronchitis), obliterating diseases of peripheral vessels (the "alternating" lameness, Reynaud's syndrome), a chronic liver and/or renal failure, a myasthenia, a pheochromocytoma, AV blockade of the I degree, a thyrotoxicosis, a depression (including in the anamnesis), psoriasis, pregnancy, advanced age.

Overdose:

Symptoms: the expressed heavy sinus bradycardia, dizziness, nausea, vomiting, cyanosis, the expressed lowering of arterial pressure, arrhythmia, a ventricular ekstasistoliya, a bronchospasm, a syncope, at acute overdose — cardiogenic shock, a loss of consciousness, a coma, an atrioventricular block (up to development of total cross block and a cardiac standstill), a cardialgia. The first signs of overdose are shown in 20 min. – the 2nd hour after administration of drug.

Treatment: a gastric lavage and purpose of the adsorbing means; symptomatic therapy: at the expressed lowering of arterial pressure – the patient has to be in the provision of Trendelenburga; in case of an excessive lowering of arterial pressure, bradycardia and heart failure — in/in, at an interval of 2-5 min., beta адреностимуляторы — 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, perhaps, purpose of 1 - 10 mg of a glucagon, statement of a transvenous intrakardialny electrostimulator. At a bronchospasm it is necessary to enter into stimulators beta 2 - adrenoceptors. Metoprolol is badly brought by means of a hemodialysis.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Not to use after the term specified on packaging. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

Tablets of 50 mg and 100 mg. On 10 tablets in the blister from AL/PVC foil. 3 blisters together with the Application instruction place in a cardboard pack.