Metoprolol

General characteristics. Structure:

Active ingredient: metoprolol;

1 tablet contains a metoprolol of tartrate, in terms of 100% substance - 25 mg or 50 mg, or 100 mg;

excipients: lactoses monohydrate, cellulose microcrystallic, кросповидон, povidone, talc, calcium stearate.

Pharmacological properties:

Pharmacodynamics. The cardioselective β-blocker, without own sympathomimetic and membranostabilizuyushchy activity, works preferential on β1-рецепторы hearts, to a lesser extent – on β2-рецепторы peripheral vessels and bronchial tubes. Has anti-hypertensive, anti-anginal and antiarrhytmic effect. Drug is characterized by negative inotropic action, reduces reduction of a myocardium, cordial emission, automatism of a sinus node, ChSS, slows down atrioventricular conductivity. Suppresses the stimulating influence of catecholamines on heart at exercise and psychoemotional stresses. At patients with coronary heart disease has antiischemic and anti-anginal effect. At an angina of exertion Metoprolol reduces quantity and weight of attacks, increases tolerance to exercise stresses; contributes to normalization of a cordial rhythm. At a myocardial infarction promotes restriction of a zone of a necrosis of a cardiac muscle; reduces risk of development of fatal arrhythmias and a recurrence of a myocardial infarction. Has anti-hypertensive effect which is stabilized by the end of the 2nd week of regular use. Unlike non-selective β-adrenoblockers Metoprolol at use in average therapeutic doses has less expressed effect on smooth muscles of bronchial tubes and peripheral arteries, insulin release, carbohydrate and lipidic metabolism.

Pharmacokinetics. Metoprolol's absorption at oral administration almost full also does not depend on meal, however bioavailability makes about 50% in connection with intensive metabolism at the first passing through a liver. At long reception bioavailability increases thanks to decrease in blood circulation in a liver and to saturation of liver enzymes. After intake the maximum concentration of drug in a blood plasma is noted in 1-2 hours. In a blood plasma Metoprolol for 5-25% contacts proteins. The elimination half-life makes 3-7 hours. At the first passing through a liver about 65-80% of drug are metabolized. It is excreted by kidneys in the form of metabolites. Metoprolol is lipophilic β-adrenoblocker.......... About 90% are soaked up in a digestive tract, well gets through a blood-brain barrier.

Main physical and chemical properties: tablets of a round form with a flat surface, color, white or white with a creamy shade, with two perpendicular crossed risks and a facet. On a surface the mramornost is allowed.

Indications to use:

– Arterial hypertension;

– stenocardia (including postinfarction);

– arrhythmias (including supraventricular tachyarrhythmia);

– the supporting treatment after the postponed myocardial infarction;

– as a part of complex therapy at a thyrotoxicosis;

– prevention of attacks of migraine.

Route of administration and doses:

Metoprolol's dose is established individually, however the daily dose should not exceed 400 mg. A pill is taken inside with a small amount of liquid, without chewing, after food. The course of treatment Metoprolol depends on features of a course of a disease and can make 3 years.

Arterial hypertension: the initial daily dose of Metoprolol makes 100 mg disposable or divided into 2 receptions. Depending on reaction of an organism it is possible to increase a daily dose gradually weekly to 200 mg. For strengthening of anti-hypertensive effect Metoprolol's use with other antihypertensives is possible.

Stenocardia: on 50-100 mg 2-3 times a day.

Arrhythmias: on 50 mg 2-3 times a day. If necessary the daily dose can be increased to 300 mg, divided into 2-3 receptions.

Hyperthyroidism (thyrotoxicosis): on 50 mg 4 times a day. At achievement of the expected effect the dose has to decrease gradually.

Myocardial infarction.

Early treatment of a pain syndrome after a myocardial infarction: on 50 mg each 6 hours within 48 hours. It is desirable to begin treatment within the first 12 hours after emergence of a stethalgia.

Maintenance therapy: the recommended daily dose – 200 mg, divided into 2 receptions. A course of treatment – not less than 3 months.

Prevention of migraine: a daily dose – 100-200 mg, divided into 2 receptions in the morning and in the evening.

Age physiological changes only slightly influence Metoprolol's pharmacokinetics, and need of correction of the mode of dosing at elderly people is absent. However it is recommended to be careful, appointing Metoprolol to patients of geriatric group.

Correction of the mode of dosing at patients with an abnormal liver function is necessary.

Dose adjustment with a renal failure is not required from patients.

Features of use:

With extra care Metoprolol apply at patients with a diabetes mellitus. At the patients accepting insulin and the tableted hypoglycemic drugs, Metoprolol can mask hypoglycemia symptoms. Metoprolol can influence the level of glucose, liver enzymes.

When carrying out a course of treatment of a pheochromocytoma Metoprolol's appointment only in a complex with a-adrenoblocker is possible.

Before carrying out surgical interventions it is necessary to inform the anesthesiologist on Metoprolol's reception (the choice of HP is necessary for the general anesthesia with the minimum negative inotropic effect), drug withdrawal is not recommended. Reciprocal activation of n.vagus can be eliminated with intravenous administration of atropine.

It is recommended to stop therapy at emergence of skin rashes and development of a depression. Patients during drug withdrawal have to be under careful observation of the doctor. Drug withdrawal is carried out gradually, reducing a dose within 10 days to 25 mg. 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 a possibility of reduction of products of the lacrimal liquid against the background of treatment by Metoprolol.

In need of Metoprolol's appointment to patients with bronchial asthma as the accompanying therapy use β2-адреностимуляторы.

With care Metoprolol apply at patients with allergic diseases, a myasthenia, a depression, vasospastic stenocardia, chronic diseases of bronchopulmonary system, psoriasis, at long starvation, a Raynaud's disease.

Patients of advanced age can find hypersensitivity even on condition of usual dosing.

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

Metoprolol can strengthen symptoms of disturbance of peripheric arterial circulation and aggravate bradycardia. At     heart rate less than 50-55 beats/min it is necessary to reduce a dose of drug or to carry out gradual drug withdrawal.

Strengthening of expressiveness of allergic reactions (against the background of the burdened allergological anamnesis) and lack of effect of introduction of usual doses of adrenaline is possible.

With extra care patients should appoint Metoprolol with Printsmetall stenocardia.

Simultaneous use of Metoprolol with inhibitors of a monoaminooxidase (MAO) is not recommended. Having rummaged in treatment between reception of MAO inhibitors and Metoprolol has to make not less than 14 days.

Control of the patients accepting β-adrenoblockers, including and Metoprolol, includes observation of ChSS and the ABP (at the beginning of reception - daily, then 1 time in 3-4 months), concentration of glucose in blood at patients with diabetes (1 time in 4-5 months). 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 elderly patients it is recommended to exercise control of function of kidneys (1 times in 4-5 months).

Ability to influence speed of response at control of motor transport or work with other mechanisms. During treatment it is necessary to be careful at control of motor transport or work with other potentially dangerous mechanisms which demands the increased concentration of attention and speed of psychomotor reactions.

Side effects:

At Metoprolol's reception are sometimes possible:

 – from cardiovascular system: bradycardia, arterial hypotension, orthostatic hypotension (sometimes with a loss of consciousness); seldom – emergence/strengthening of symptoms of heart failure (especially at increase in a dose of drug), arrhythmia, tachycardia, hypostases, Reynaud's syndrome; very seldom –                        AV conductivity disturbance, pain in heart, gangrene (at patients with heavy disturbance of peripheric circulation);

– from a respiratory organs: an asthma at loading; seldom – a bronchospasm; very seldom – rhinitis;

– from the central and perifericheskoynervny system: dizziness, headache; seldom – disturbance of concentration of attention, a depression, nightmares, sleeplessness or drowsiness, paresthesias; very seldom – hallucinations, change of the personality, the increased excitement, confusion of consciousness;

– from sense bodys: seldom – decrease in sight, reduction of secretion of the lacrimal liquid, dryness and irritation of a mucous membrane of eyes, conjunctivitis, a sonitus, decrease in hearing;

– from a digestive tract: nausea, vomiting, abdominal pain; seldom – diarrhea, a lock; very seldom – dryness in a mouth; in some cases – retroperitoneal fibrosis (however accurate relationship of cause and effect between this reaction and Metoprolol's reception is not established);

– from system of a hemopoiesis: seldom – thrombocytopenia, a leukopenia;

– allergic reactions: seldom – skin rash (including urtikarny, psoriazopodobny, dystrophy of a hypodermic fatty tissue), an itch, urticaria; very seldom – a photosensitization, sweating strengthening, a reversible alopecia, an exacerbation of psoriasis;

– laboratory indicators: increase in activity of "hepatic" enzymes, a hyperbilirubinemia, increase in level of triglycerides in blood, reduction of level of lipoproteins of the high density (HDL);

– others: weakness, fatigue (is more often in an initiation of treatment), hepatitis, nonspecific muscle, joints pain, spasms; very seldom – arthritis, increase in body weight, disturbance of a libido, impotence; in some cases – Peyroni's disease (however accurate relationship of cause and effect between this reaction and Metoprolol's reception is not established).

Interaction with other medicines:

At a concomitant use of Metoprolol with 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 or disappear. In such cases it is necessary to carry out regular control of level of glucose to blood.

At simultaneous use of Metoprolol and barbiturates, fenotiazin, nitroglycerine, diuretics, vazodilatator and other antihypertensives (for example, Prazozinum), peroral contraceptives – the hypotensive effect can amplify.

At a concomitant use of Metoprolol with the drugs inhibiting CYP2D6 enzyme oppression of metabolism of Metoprolol, increase in its concentration in a blood plasma and increase in risk of development of toxic effects is possible. Treat such drugs: antidepressants (fluoxetine, пароксетин, бупропион), antipsychotic (thioridazine), anti-retrovirus (ритонавир), antihistaminic (дифенгидрамин), anti-malarial (hydroxychloroquine, гуинидин), antifungalny (тербинафин), ranitidine, Cimetidinum.

Cardiac glycosides, Methyldopum, Reserpinum and гуанфацин, blockers of slow calcium channels (verapamil, diltiazem), Amiodaronum, пропафенон and other antiarrhytmic HP increase risk of development or aggravation of bradycardia,                AV blockade, a cardiac standstill and heart failure. At Metoprolol's use contraindicated intravenous administration of drugs of a class of verapamil (threat of a cardiac standstill); at Metoprolol's use and peroral forms of drugs of a class of verapamil it is necessary to be especially careful.

At joint treatment by a clonidine and Metoprolol treatment by the last has to be stopped some days before cancellation of a clonidine for prevention of hypertensive crisis.

Careful control of patients at a concomitant use of Metoprolol with ganglioblokator, other β-blockers is necessary ((((((((((for example, eye drops) or MAO inhibitors.

At simultaneous use with Norepinephrinum, Epinephrinum, others adreno-and sympathomimetics (including in the form of eye drops or as a part of antibechics) perhaps some increase in the ABP.

At simultaneous use with indometacin and rifampicin Metoprolol's concentration in a blood plasma decreases.

At simultaneous use of Metoprolol with lidocaine disturbance of removal of the last is possible.

Iodinated X-ray contrast HP for intravenous administration increase risk of development of anaphylactic reactions.

At simultaneous use with ergotamine strengthening of disturbances of peripheric circulation is possible.

At simultaneous use of Metoprolol and peripheral muscle relaxants (for example, succinylcholine, tubocurarine) strengthening of neuromuscular blockade is possible.

Drugs strengthen hypotensive effect of Metoprolol. At the same time negative inotropic effect of the specified means is exponentiated. Therefore before operation under the general anesthesia the anesthesiologist has to be informed on what the patient accepts Metoprolol. At simultaneous use with opioid analgetika the cardiodepressive effect mutually amplifies.

Metoprolol can cause small reduction of clearance of theophylline in the smoking patients.

At simultaneous use Metoprolol increases concentration of ethanol in blood and extends its removal.

Contraindications:

– Hypersensitivity to a metoprolol, other b-blockers or other ingredients of drug;

– bronchial asthma or a bronchospasm in the anamnesis;

– atrioventricular block of the II-III degree;

– acute or chronic (the IV functional class on NYHA) heart failure;

– clinically significant sinus bradycardia;

– syndrome of weakness of a sinus node;

– heavy disturbance of peripheric circulation;

– cardiogenic shock;

– arterial hypotension;

–  pheochromocytoma;

–  metabolic acidosis;

–  heavy insufficiency of function of a liver;

– children's age.

Metoprolol patients should not appoint with suspicion of an acute myocardial infarction at heart rate less than 45 beats/min., P–Q interval> 0,24 c or systolic arterial pressure <100 mm hg.

Use during pregnancy or feeding by a breast. Use of drug during pregnancy is possible only in the presence of vital indications and provided that the expected advantage for the woman exceeds potential risk for a fruit (in connection with possible development in the fruit/newborn of bradycardia, hypotension, a hypoglycemia). This fact needs to be taken into account, appointing drug during the last trimester. Use of drug should be stopped at least in 2-3 days prior to childbirth.

Metoprolol is allocated in breast milk. However at its use by the women nursing in therapeutic doses the negative impact on the baby is improbable.

At Metoprolol's appointment the pregnant women and women nursing need to pick up a minimal effective dose.

Children. Metoprolol's use at children's age is contraindicated.

Overdose:

Simptomy:tyazhely hypotension, bradycardia, atrioventricular block, heart failure, cardiogenic shock, cardiac standstill, bronchospasm, disturbance of consciousness or lump, spasm, nausea, vomiting, cyanosis, hypoglycemia, hyperpotassemia.

Treatment. At overdose it is necessary to wash out a stomach or to cause vomiting, to accept absorbent carbon. It is necessary to see a doctor. At development of heavy hypotension, bradycardia or threat of heart failure it is necessary to appoint адреномиметик, to enter intravenously 1-2 mg of Atropini sulfas. If after that there is no necessary improvement, purpose of pressor means is possible. In case of severe forms of hypotension, bradycardia or threat of heart failure it is necessary to enter β1-агонист (for example, преналтерол). In case of lack of the selection β1-агониста it is possible to enter sympathomimetic agents intravenously (for example, noradrenaline, dopamine, Dobutaminum). It is possible to enter a glucagon. There can be a need of use of the driver of a cordial rhythm. For stopping of a bronchospasm it is necessary to enter intravenously β2-агонист.

Storage conditions:

Period of validity 3 years. In original packaging, at a temperature not over 25 ºС. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister. 3 blisters in a pack.