Метопролол-Акри®

General characteristics. Structure:

Active ingredient: 0,05 g of a metoprolol of tartrate in 1 tablet.

Excipients: lactose (sugar milk), silicon dioxide colloid, potato starch, povidone, starch sodium glycollate, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Metoprolol affects preferential heart beta1-adrenoceptors. Has no membrane stabilizing effect and has no internal sympathomimetic activity.

Possesses anti-anginal, anti-hypertensive and antiarrhytmic action. Reduces automatism of a sinus node, urezhat the heart rate (HR), slows down atrioventricular conductivity, reduces contractility and excitability of a myocardium, cordial emission, the need of a myocardium for oxygen. Suppresses the stimulating effect of catecholamines on heart at exercise and psychoemotional stress.

The anti-hypertensive effect develops gradually and is stabilized by the end of the 2nd week of course appointment. At an angina of exertion ^{of Metoprolol-Akri®} reduces the frequency and weight of attacks. Normalizes a cordial rhythm at supraventricular tachycardia and atrial fibrillation. ^{Метопролол-Акри®} reduces mortality and possibility of a recurrence at patients with a myocardial infarction owing to restriction of a zone of a heart attack and reduction of risk of development of fatal arrhythmias. At use in average therapeutic doses exerts less expressed impact on smooth muscles of bronchial tubes and peripheral arteries, than non-selective beta адрено - blockers.

Pharmacokinetics. Absorption at intake full (95%). Solubility in fats moderate. Is exposed to intensive presistemny metabolism, bioavailability - 50% at the first reception and increases up to 70% at repeated use. Communication with proteins of a blood plasma - 10%. Time of achievement of the maximum concentration of a metoprolol in a blood plasma makes 1,5-2 h after reception of tablets. During course treatment bioavailability increases. Meal increases bioavailability for 20-40%.

It is quickly distributed in fabrics, gets through a blood-brain barrier, a placental barrier. Gets into maternal milk (concentration higher, than in plasma). Is not removed at a hemodialysis.

It is metabolized in a liver, two metabolites have beta and adrenoceptor blocking activity. The elimination half-life of a metoprolol makes from 3,5 to 7 h at intake. Considerable accumulation of metabolites is observed at patients with clearance of creatinine of 5 ml/min., at the same time beta and adrenoceptor blocking activity of drug does not increase. The fermental P450 CYP2D6 system takes part in metabolism of drug. Over 95% in/in the entered dose are allocated with kidneys, 3-10% in an invariable look.

Bioavailability increases at cirrhosis, at the same time its general clearance is reduced (patients with the imposed porto-caval anastomosis have the general clearance later in/in introductions about 0,3 l/min, and AUC - is 6 times higher, than at healthy people).

Indications to use:

Arterial hypertension, the coronary heart disease (CHD), secondary prevention after the postponed myocardial infarction, disturbances of a heart rhythm (supraventricular tachycardia, ventricular premature ventricular contraction), a hyperkinetic cardial syndrome, prevention of attacks of migraine.

Route of administration and doses:

Inside, with food or right after food. The tablet is swallowed, without chewing, and wash down with a small amount of liquid. Treatment begin with a dose 50 mg in 1-2 receptions. At insufficient expressiveness of therapeutic effect the daily dose is gradually increased to 200 mg. Maximum daily dose of 200 mg.

At arterial hypertension an average dose — 100-150 mg/days in 1-2 receptions, if necessary — 200 mg/days.

At stenocardia — 50 mg 2-3 times a day.

At a hyperkinetic cardial syndrome (at a thyrotoxicosis, vegeto-vascular dystonia) — 50 mg 1-2 times a day.

At a tachyarrhythmia — 50 mg 2-3 times a day, if necessary — 200 mg/days.

Secondary prevention of a myocardial infarction — 200 mg/days.

Prevention of migraine — 100-200 mg/days in 2-4 receptions.

Elderly patients are recommended to begin treatment with 50 mg/days.

Features of use:

At arterial hypertension the effect occurs in 2-5 days, the stable state is noted in 1-2 months.

At an angina of exertion the picked-up dose of drug has to provide ChSS at rest within 55-60 уд. / mines, at loading - no more than 110 уд. / min.

At smokers efficiency of beta adrenoblockers is lower. Monitoring of the patients accepting beta adrenoblockers includes observation of ChSS and the ABP (at the beginning of reception - daily, then 1 time in 3-4 months), the content of glucose of blood at patients with a diabetes mellitus (1 time in 4-5 months).

If necessary for patients with a diabetes mellitus the dose of insulin or the antidiabetic means appointed inside should be selected 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 уд. / min. At elderly patients it is recommended to exercise control of function of kidneys (1 times in 4-5 months).

Can strengthen symptoms of disturbance of peripheric arterial circulation.

Drug withdrawal is carried out gradually, reducing a dose within 10 days, under observation of the doctor. At the sharp termination of treatment there can be a syndrome of "cancellation" (strengthening of attacks of stenocardia, increase in the ABP). Special attention at drug withdrawal needs to be paid to patients with stenocardia.
The patients using contact lenses have to consider that against the background of treatment ^{by the drug Metoprolol-Akri®} reduction of products of the lacrimal liquid is possible.

^{Метопролол-Акри®} 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 ^{of Metoprolol-Akri®} 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.

At elderly patients it is recommended to carry out 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 (less than 50 уд. / mines), the expressed decrease in the ABP (systolic pressure is lower than 100 mm hg), an atrioventricular block, 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 ^{Metoprolol-Akri®}; in case of development of the depression caused by reception of beta adrenoblockers it is recommended to stop therapy.

For several days before carrying out an anesthesia chloroform or ether it is necessary to stop administration of drug. 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.

At a combination therapy with a clonidine reception of the last should be stopped in several days after cancellation ^{of Metoprolol-Akri®} in order to avoid hypertensive crisis. At a dose higher than 200 mg/days decrease cardioselectivity.

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 is possible.

In need of appointment to patients with bronchial asthma, as the accompanying therapy use beta2-adrenosti-mulyatory, at a pheochromocytoma — alpha adrenoblockers.

Reciprocal activation of a vagus nerve can be eliminated in/in administration of atropine (1-2 mg).

Caution. During treatment it is necessary to abstain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions; to exclude ethanol reception.

Use during pregnancy and during feeding by a breast. During pregnancy (especially in the first 3 months) ^{Metoprolol-Akri®} has to be applied only according to strict indications after careful correlation of advantage and risk as so far there is no sufficient experience of its use at pregnancy. If pregnant women accepted ^{Metoprolol-Akri®}, then in connection with a possibility of emergence in the newborn of bradycardia, arterial hypotension, a hyperglycemia stop treatment in 48-72 hours before childbirth. If it is impossible, then the newborn has to be under especially careful observation within 48-72 hours after the delivery. Metoprolol gets into breast milk. Use ^{of the drug Metoprolol-Akri®} during feeding is contraindicated.

Side effects:

From a nervous system: weakness, fatigue, dizziness, a headache, delay of speed of mental motor reactions, muscular spasms, a cryesthesia, paresthesias in extremities (at patients with the "alternating" lameness and Reynaud's syndrome), a tremor, concern, decrease in attention, drowsiness, a depression, sleeplessness, dreadful dreams, confusion of consciousness or short-term loss of memory, a hallucination, an asthenic syndrome, muscular weakness.

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

From cardiovascular system: the expressed decrease in the ABP, decrease in contractility of a myocardium, disturbance of a heart rhythm, aggravation of earlier existing disturbances of atrioventricular conductivity, bradycardia, orthostatic hypotension (sometimes with a loss of consciousness), emergence of symptoms of heart failure with peripheral hypostases (stop and/or the lower part of shins), an asthma, a cardialgia.

From the alimentary system: nausea, vomiting, abdominal pains, dryness in a mouth, diarrhea, a lock. Separate cases of abnormal liver functions, taste changes are noted.

From integuments: enanthesis (exacerbation of psoriasis), psoriazopodobny skin reactions, dermahemia, dieback, photodermatosis, sweating strengthening, reversible alopecia.

Allergic reactions: skin itch, small tortoiseshell.

From respiratory system: nose congestion, asthma. Predisposed patients have a bronchospasm.

From endocrine system: a hyperglycemia (at patients with a non-insulin-dependent diabetes mellitus), hypoglycemic states at patients with a diabetes mellitus, a hypothyroid state.

Laboratory indicators: thrombocytopenia, leukopenia, agranulocytosis, increase in activity of "hepatic" enzymes, hyperbilirubinemia.

Influence on a fruit: pre-natal growth inhibition, hypoglycemia, bradycardia.
Others: a dorsodynia or joints, insignificant increase in body weight, decrease in a potentiality, libido, at the sharp termination of treatment - a syndrome of "cancellation".

Interaction with other medicines:

At a concomitant use ^{of the drug Metoprolol-Akri®} and
- insulin or peroral antihyperglycemic means their action can amplify or be prolonged. At the same time hypoglycemia symptoms (especially, tachycardia and a tremor) can mask;
- tricyclic antidepressants, barbiturates, fenotiazin, nitroglycerine the hypotensive effect can amplify;
- blockers of "slow" calcium channels (type nifedipine) except strengthening of hypotensive effect, heart failure can develop;
- blockers of "slow" calcium channels (verapamil and diltiazem), Amiodaronum or other antiarrhytmic means arterial hypotension, bradycardia (development or aggravation of a current), disturbances of a heart rhythm, AV blockade, heart failure, a cardiac standstill can develop;
- cardiac glycosides, Reserpinum, alpha Methyldopums, a guanfatsin and a clonidine there can be a dangerous decrease in ChSS;
- Norepinephrinum, Epinephrinum or other sympathomimetic means (for example, contained in eye drops or antibechics) increase in arterial pressure is possible;
- indometacin and rifampicin anti-hypertensive effect ^{of the drug Metoprolol-Akri®} can decrease;
- Cimetidinum strengthening of effect ^{of the drug Metoprolol-Akri®} is possible;
- lidocaine the clearance of the last decreases;
- drugs the hypotensive effect amplifies. At the same time the additive, negative inotropic action of both means is shown;
- competitive muscle relaxants (for example, succinylcholine, tubocurarine) there can be strengthening of nervnomyshechny blockade;
- alcohol strengthening of the slowing-down action is possible;
- the allergens used for an immunotherapy, or extracts of allergens for skin tests the risk of emergence of heavy system allergic reactions or an anaphylaxis increases;
- yodosoderzhashchy radiopaque substances for in/in introductions the risk of development of anaphylactic reactions increases;
- Phenytoinum at in introduction, means for an inhalation anesthesia (derivative hydrocarbons) expressiveness of cardio-depressive action and probability of decrease in the ABP increases;
- non-steroidal anti-inflammatory drugs (NPVP) (delay of sodium and blockade of synthesis of prostaglandin kidneys), glucocorticosteroids (GKS) and estrogen (sodium delay) easing of hypotensive effect;
- diuretics, sympatholytics, a gidralazin and other antihypertensives can lead to excessive decrease in the ABP;
- rub - and tetracyclic antidepressants, antipsychotic means (neuroleptics), sedative and hypnagogues oppression of the central nervous system amplifies;
- not hydrogenated alkaloids of an ergot the risk of development of disturbance of peripheric circulation increases.

^{Метопролол-Акри®} reduces clearance of xanthines (except Diphyllinum) and increases their concentration in plasma, especially at patients with initially increased clearance of theophylline under the influence of smoking.

The anticoagulating effect of coumarins extends action.

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.

Contraindications:

Hypersensitivity to drug, an atrioventricular block of II and III degrees, sinuatrial blockade, the expressed bradycardia, arterial hypotension (in case of use at secondary prevention of a myocardial infarction — systolic the ABP less than 100 mm hg), Printsmetal's stenocardia, a sick sinus syndrome, chronic heart failure of IIB-III of a stage, heart failure in decompensation stages, cardiogenic shock, a concomitant use with MAO inhibitors, the lactation period, an acute myocardial infarction (PQ more than 0,24 sec. or systolic the ABP less than 100 mm hg).

With care: a diabetes mellitus, obliterating diseases of peripheral vessels (" the lameness alternating", Reynaud's syndrome), a myasthenia, a pheochromocytoma, an atrioventricular block of the I degree, a thyrotoxicosis, a depression (including in the anamnesis), psoriasis, pregnancy, age up to 18 years (efficiency and safety are not established), advanced age, a metabolic acidosis, bronchial asthma, HOBL (emphysema of lungs, chronic obstructive bronchitis), the chronic renal failure (CRF) expressed an abnormal liver function and kidneys (at purpose ^{of the drug Metoprolol-Akri®} of this category of patients constant control behind dynamics of a functional condition of a liver and/or kidneys is necessary).

Overdose:

Symptoms: the clinical picture depends on degree of intoxication and is shown, generally by disturbances from cardiovascular and central nervous systems. The overdose can lead to the expressed decrease in the ABP, bradycardia (up to a cardiac standstill), to heart failure and cardiogenic shock. In hard cases breath difficulty, a bronchospasm, vomiting, consciousness disturbances, generalized convulsive attacks can be observed.

Treatment: in cases of overdose or at the menacing falling of heart rate and/or the ABP, treatment ^{with the drug Metoprolol-Akri®} is interrupted. In the conditions of intensive care unit in addition to the actions directed to removal from an organism of a metoprolol make careful observation of vital parameters and in need of them korrigirut.

If necessary appoint:
- atropine;
- glucagon;
- sympathomimetics depending on body weight and the gained effect (a dopamine, Dobutaminum, изопреналин, оксипреналин or adrenaline);
- at refractory therapy of bradycardia it is possible to transfer the patient to electrocardiostimulation temporarily;
- at a bronchospasm appoint beta2-adrenomimetik in the form of an aerosol (at insufficiency of effect also in/in) or Aminophyllinum in / century. At generalized convulsive attacks appoint diazepam (in/in, slowly).

Storage conditions:

List B. In dry, protected from light and the place, unavailable to children, at a temperature not over 25 to the °sena to use after the date specified on packaging. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

Tablets on 0,05 g. On 10 tablets in a blister strip packaging. 2, 3 or 5 blister strip packagings together with the application instruction in a cardboard pack.