Metoprolola tartrate

General characteristics. Structure:

Active ingredient: metoprolol;

1 tablet contains a metoprolol of tartrate of 50 mg (0,05 g) or 100 mg (0,1 g) in terms of dry    100% substance;

excipients: potato starch, lactoses monohydrate, magnesium stearate, silicon dioxide colloid anhydrous.

Pharmacological properties:

Pharmacodynamics. Metoprolola tartrate is cardioselective β-adrenoblocker without internal sympathomimetic activity and membrane stabilizing action. Influences preimuyoshchestvenno on β1-адренорецепторы hearts, has anti-anginal, hypotensive and antiarrhytmic effects. At the patients who had a myocardial infarction reduces risk of a repeated myocardial infarction, and at patients with arterial hypertension - also reduces risk of cardiovascular complications (stroke). Its anti-ischemic action in case of bezbolevy ischemia of a myocardium and reduction of a hypertrophy of a left ventricle at patients with arterial hypertension is proved.

The anti-anginal effect is caused by reduction of heart rate, contractility of a myocardium, system arterial pressure that leads to reduction of need of a myocardium for oxygen. Thanks to lengthening of a diastole (owing to negative chronotropic effect), perfusion of a myocardium improves. Unlike non-selective β-adrenoblockers of Metoprolol tartrate 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. After intake Metoprolol's absorption of tartrate from digestive tract almost full (90%) also does not depend on meal, but bioavailability makes about 50% in connection with intensive metabolism at the first passing through a liver (65-80%). At long use bioavailability increases thanks to decrease in blood circulation in a liver and to saturation of liver enzymes. The maximum concentration of drug in a blood plasma is registered in 1-2 h, but influence on arterial pressure and heart rate is observed (after a single dose of 100 mg) for 12 h.

Elimination half-life – 3-7 h. At a renal failure it increases to 27 h and more. It is excreted by kidneys in the form of metabolites. At a liver failure drug can kumulirovat in an organism. It well gets through hematoencephalic, placental barriers and into breast milk. Smoking, alcohol intake, reception of some medicines changes Metoprolol's metabolism of tartrate (for example, barbiturates, dipheninum, rifampicin – raise, Chlorpromazinum – reduces). Biotransformation in a liver decreases at cirrhosis therefore to such patients the dose is reduced, and concentration in a blood plasma – is controlled.

Pharmaceutical characteristics.

Main physical and chemical properties: tablets of white color, with a flat surface, risky and a facet. On a surface of tablets gray impregnations are allowed.

Indications to use:

Arterial hypertension; stenocardia (including postinfarction); arrhythmias (including supraventricular tachycardia); prevention of cordial death and a repeated heart attack after an acute phase of a myocardial infarction. As a part of complex therapy at a thyrotoxicosis. Prevention of attacks of migraine.

Route of administration and doses:

Metoprolol's dose of tartrate is established individually. The maximum daily dose – 400 mg.

Pill is taken inside, with a small amount of liquid, without chewing, after food.

Duration of a course of treatment is established individually and can make 3 years.

At arterial hypertension the initial dose makes 100 mg a day disposable or divided into two receptions (in the morning and in the evening). If necessary it is possible to increase a daily dose to 200 mg.

At stenocardia appoint 50-100 mg of Metoprolol of tartrate 2-3 times a day.

At arrhythmias appoint 50 mg 2-3 times a day. If necessary the daily dose is increased to 300 mg, divided into 2-3 receptions.

At a hyperthyroidism (thyrotoxicosis) appoint 50 mg 4 times a day. At achievement of therapeutic effect the dose is gradually reduced.

At a myocardial infarction (treatment it is desirable to begin within the first 12 hours after emergence of a stethalgia): on 50 mg each 6 hours within 48 hours, the supporting recommended daily dose – 200 mg, divided into 2 receptions. A course of treatment – not less than 3 months.

Prevention of attacks of migraine: appoint Metoprolol tartrate in a dose of 100-200 mg a day, divided into 2 receptions.

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

Dose adjustment is not necessary to patients of advanced age and patients with a renal failure.

Features of use:

At reception of a metoprolol of tartrate, as well as at reception of other β-blockers, it is necessary to control the heart rate (HR) and the arterial pressure (AP) (at first daily, then once a month).

To the patients accepting β-blockers, it is not necessary to enter intravenously verapamil.

Especially careful medical control is necessary at treatment of patients with a diabetes mellitus      (control of level of glucose in blood), patients with the unstable level of sugar in blood, at observance of a rigid diet with starvation. Manifestation of latent diabetes or an aggravation of symptoms of patients with a diabetes mellitus is in rare instances possible. At treatment metoprololy risk of influence on metabolism of carbohydrates or risk of emergence of the hidden hypoglycemia smaller, than at use of non-selective β-blockers..........

Metoprolola tartrate can mask some clinical displays of a thyrotoxicosis (for example tachycardia). Sharp drug withdrawal at patients with a thyrotoxicosis is contraindicated because of possible strengthening of symptomatology.

The patient with a pheochromocytoma at treatment Metoprolol with tartrate it is necessary to appoint α-adrenoblockers at the same time..........

Before carrying out surgical interventions it is necessary to warn the anesthesiologist about reception of a metoprolol of tartrate. It is not recommended to stop treatment.

It is necessary to stop treatment by drug gradually, reducing a dose for 10 days to   25 mg. At sudden drug withdrawal there can be a syndrome of "cancellation" (strengthening of attacks of stenocardia, increase in arterial pressure).

At heart rate less than 50-55 beats/min the dose of drug has to be reduced or gradually cancelled.

In need of purpose of drug to patients with bronchial asthma, perhaps, there will be necessary an increase in a dose of stimulators β2-рецепторов.

At use of a metoprolol of tartrate strengthening of expressiveness of allergic reactions and lack of effect at introduction of usual doses of adrenaline is possible. The acute anaphylaxis at the patients accepting blockers of β-adrenoceptors, has a heavy current.

Patients who use contact lenses should consider that drug can reduce secretion of the lacrimal liquid.

With care patients should use drug with a myasthenia, a depression, vasospastic stenocardia, chronic diseases of bronchopulmonary system, psoriasis, a Raynaud's disease; to patients of advanced age (control of function of kidneys).

Special observation is demanded by patients with stenocardia. With extra care it is necessary to appoint метопролол the patient with Printsmetall stenocardia.

Metoprolol can lead to an exacerbation of diseases of peripheral arteries, such as the alternating lameness.

To patients with heavy renal failures, with serious acute states which are followed by a metabolic acidosis and to patients who receive the combined treatment by foxglove drugs it is necessary to pay special attention.

Drug contains lactose therefore it is not necessary to appoint it the patient with hereditary deficit of lactase, intolerance of a galactose or with disturbances of metabolism of a glucose/galactose.

Ability to influence speed of response at control of motor transport or work with other mechanisms.

 

During treatment by drug it is necessary to abstain from control of motor transport or work with other potentially dangerous technical means.

Side effects:

From the central nervous system: dizziness, a headache, a depression, a sleep disorder (dreadful dreams), insomnia, change of mood, a short-term memory impairment, feeling of numbness of skin and crawling of goosebumps, cold sense in extremities, confusion of consciousness, a hallucination, hypererethism, nervousness, uneasiness, deterioration in concentration of attention, frustration of the personality.

From digestive tract: the dispeptic phenomena (nausea, vomiting, diarrhea, a lock), heartburn, abdominal pains, a meteorism, dryness in a mouth, retroperitoneal fibrosis (accurate relationship of cause and effect between this reaction and reception of a metoprolol it is not established).

From gepatobiliarny system: hepatitis.

From system of breath: at some patients an asthma at an exercise stress can be noted, cough, a bronchospasm, attacks of bronchial asthma (at patients with bronchial asthma), rhinitis.

From cardiovascular system: arterial hypotension, delay of pulse, an atrioventricular block of II and III degrees, AV conductivity lengthening, deterioration in symptoms of heart failure, pain in heart, the strengthened heartbeat, bradycardia, increase of attacks of stenocardia, cardiogenic shock at patients with an acute myocardial infarction, peripheral hypostases, Reynaud's syndrome, arrhythmia, is possible also strengthening of the available frustration of peripheric circulation (up to gangrene), strengthening of symptoms of the alternating lameness.

From sense bodys: decrease in sight, conjunctivitis, reduction of secretion of the lacrimal liquid (it is necessary to consider this circumstance to patients who carry contact lenses), decrease in hearing (sonitus).

Allergic reactions: itch, skin rash (in most cases psoriazoformny or dystrophic damages of skin), urticaria, hair loss, skin photosensitization, exacerbation of psoriasis.

From endocrine system: at patients with a diabetes mellitus the hypoglycemia can develop.

From system of a hemopoiesis: thrombocytopenia, leukopenia, agranulocytosis.

Changes of laboratory indicators: increase in activity of "hepatic" enzymes, a hyperbilirubinemia, increase in level of triglycerides in blood, reduction of level of lipoproteins of high density, emergence of the antinuclear antibodies (which are not connected with a system lupus erythematosus).

Others: increased fatigue, strengthening of a potovydeleniye, nespetsifichesy muscle, joints pain, muscular spasms, spasms, arthritis, increase in body weight, disturbance a libido, impotence, Peyroni's disease (accurate relationship of cause and effect between this reaction and reception of a metoprolol of tartrate it is not established).

Interaction with other medicines:

At a concomitant use of Metoprolol of tartrate 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.

Metoprolol is substrate of CYP 2D6 enzyme. The drugs inhibiting CYP 2D6, for example, quinidine, тербинафин, пароксетин, fluoxetine, sertraline, целекоксиб, пропафенон and дифенгидрамин can influence concentration of a metoprolol in a blood plasma. In an initiation of treatment reduction of a dose of Metoprolol of tartrate can be these drugs necessary.

It is necessary to avoid a concomitant use of Metoprolol of tartrate with following drugs:

Derivatives of barbituric acid: barbiturates (it is investigated for pentobarbital) stimulate metabolism of a metoprolol by enzyme induction.

Propafenon: at four patients who received treatment metoprololy after reception of a propafenon of concentration of a metoprolol in a blood plasma increased by 2 - 5 times, and two patients had side effects typical for a metoprolol. Interaction was confirmed at eight healthy volunteers. This interaction, perhaps, is explained by the fact that пропафенон, like quinidine, oppresses metabolism of a metoprolol through system of P450 2D6 cytochrome. Result of such combination unpredictable as пропафенон also has    the β-blocking properties.

Verapamil: in a combination with β-blockers ((((((((((it is described for an atenolol, propranolol and Pindololum) verapamil can cause bradycardia and a lowering of arterial pressure. Verapamil and               β-blockers possess the additive inhibitory action on atrioventricular conductivity and function of a sinus node.

Simultaneous use of Metoprolol of tartrate with following drugs can demand correction of doses:

Amiodaronum: at patients who accept Amiodaronum the expressed sinus bradycardia at simultaneous use with metoprololy can develop. Amiodaronum has extremely long elimination half-life (about 50 days), it means that interaction can arise after cancellation of this drug for a long time.

Antiarrhytmic drugs of a class I: antiarrhytmic means of the I class and b-blockers possess the additive negative inotropic action that can result in serious hemodynamic side effects at patients with the broken function of a left ventricle. Also it is necessary to avoid use of this combination at a sick sinus syndrome and disturbance of AV conductivity. Such interaction is best of all described for a dizopiramad.

Nonsteroid antiinflammatory and antirheumatic drugs: it is shown that NSPVP counteract anti-hypertensive action of b-blockers. Mainly, studied indometacin. It is probable that this interaction does not happen with sulindaky. The research of negative interaction was conducted with diclofenac.

Foxglove glycosides: the concomitant use of glycosides of a foxglove and blockers of β-receptors can increase time of atrioventricular conductivity and cause bradycardia.

Difengidramin: дифенгидрамин reduces (by 2,5 times) clearance of a metoprolol to an alpha gidroksimetoprolola through the CYP 2D6 system at persons who have a bystry gidroksilyation. Effects of a metoprolol amplify. It is possible what дифенгидрамин can inhibit metabolism of other CYP 2D6 substrates.

Diltiazem: diltiazem and blockers of β-receptors possess the additive inhibiting effect on AV conductivity and function of a sinus node. At treatment diltiazem observed (messages on cases) the expressed bradycardia.

Epinephrinum: after introduction of Epinephrinum (adrenaline) to patients who applied non-selective blockers of β-receptors ((((((((((including Pindololum and propranolol) the expressed hypertensia and bradycardia (about 10 messages) developed. At separate states when adrenaline is appointed to patients who are treated by β-blockers, use of cardioselective β-blockers influences blood pressure, in comparison with non-selective β-blockers less..........

Fenilpropanolamin: фенилпропаноламин (норефедрин) in a single dose of 50 mg can lead to pathological increase in diastolic arterial pressure at healthy volunteers. Propranolol generally interferes with increase in arterial pressure fenilpropanolaminy. However blockers of β-receptors can provoke paradoxical hypertensive reactions at patients who apply high doses of a fenilpropranolamin. In two cases hypertensive crisis was described during treatment of a tolka fenilpropanolaminy.

Quinidine: quinidine inhibits metabolism of a metoprolol at so-called bystry metabolizator with substantial increase of levels in a blood plasma and thereof, strengthening of blockade      of β-receptors.......... The corresponding interaction can be observed with other β-blockers, which are metabolized by the same enzyme (P450 2D6 cytochrome).

Clonidine: β-blockers can exponentiate hypertensive reaction at sudden cancellation of a clonidine. In case it is necessary to cancel the accompanying therapy by a clonidine, the β-blocker should be cancelled some days before cancellation of a clonidine.

Nitroglycerine: joint use can lead to sharp hypotonia.

Rifampicin: rifampicin can stimulate metabolism of a metoprolol that leads to reduction of its levels in a blood plasma.

Patients who receive along with Metoprolol tartrate other β-blockers ((((((((((for example, eye drops) or monoamine oxidase inhibitors (MAO), have to be under careful observation. Purpose of inhalation anesthetics to patients who receive treatment by blockers of β-receptors, strengthens cardiodepressive effect. Concentration of a metoprolol in a blood plasma can increase if are at the same time entered Cimetidinum or гидралазин.

Contraindications:

Hypersensitivity to a metoprolol, other β-blockers or other components of drug. Atrioventricular block of II and Sh degrees, cardiogenic shock; heart failure in a decompensation stage (a fluid lungs, a syndrome of hypoperfusion or hypotension); long or periodic inotropic therapy by agonists of β-receptors;;;;;;;;;; clinically significant sinus bradycardia; sick sinus syndrome; the expressed arterial hypotension, a metabolic acidosis; heavy disturbances of peripheric circulation; bronchial asthma or a bronchospasm in the anamnesis; heavy insufficiency of function of a liver; a serious illness of peripheral vessels with threat of gangrene, not treated pheochromocytoma.

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

Overdose:

Symptoms: bradycardia, AV blockade of the I-III degree, lengthening of an interval of QT, an asystolia, a lowering of arterial pressure, insufficient peripheral perfusion, heart failure, cardiogenic shock, a bronchospasm, respiratory depression, an apnoea, fatigue, confusion of consciousness, a loss of consciousness, a melkorazmashisty tremor, spasms, the increased perspiration, paresthesias, nausea, vomiting, an esophagospasm, a hypoglycemia (especially at children) or a hyperglycemia, influence on kidneys, a temporary myasthenic syndrome. Simultaneous alcohol intake, hypotensive drugs, quinidine or barbiturates can worsen a condition of the patient. The first signs of overdose can be observed in 20 minutes – 2 hours after administration of drug.

Treatment: hold events of the general detoxication (a gastric lavage, reception of absorbent carbon and purgatives). NB! Atropine (0,25-0,5 mg of intravenously adult, 10-20 mkg/kg of body weight – children) should enter to a gastric lavage (in connection with risk of vagal stimulation). The intubation and use of the device artificial дыхання can be necessary; adequate recovery of volume of the circulating blood; glucose infusion; monitoring of an ECG; repeated intravenous administration of atropine of 1-2 mg (mainly at vagal symptoms). At oppression of function of a myocardium: infusion of Dobutaminum or dopamine and calcium of a glubionat of 9 mg/ml, 10-20 ml. It is possible to enter a glucagon of 50-150 mkg/kg intravenously within 1 minute with the subsequent infusion, and also амринон. In certain cases there was effective an addition of adrenaline (Epinephrinum). Sodium infusion (chloride or bicarbonate) when lengthening a QRS complex and arrhythmia. It is possible to use a pacemaker. At a stop of blood circulation actions for resuscitation within several hours can be necessary. At a bronchospasm appoint тербуталин (an injection or inhalation). Symptomatic therapy.

Use during pregnancy or feeding by a breast.

During pregnancy (especially in the I trimester) to apply Metoprolol tartrate in the presence of vital indications and only when the expected therapeutic effect exceeds potential risk for a fruit. Due to the possible development in the newborn child of bradycardia, arterial hypotension, a hypoglycemia and a depression of breath the course of treatment needs to be interrupted in 48-72 hours prior to childbirth. The quantity of a metoprolol of tartrate which the child through breast milk can receive with small probability, will result in the β-blocking effects if mother accepts drug in usual therapeutic doses. However it is necessary to be careful, appointing β-blockers to mothers nursing and to watch the child for early detection of the β-blocking effects.

Children.

Metoprolol's use of tartrate is contraindicated to children.

Storage conditions:

Period of validity 3 years. Not to use drug after the termination of the period of validity specified on packaging. To store in protected from light and the place, unavailable to children, at a temperature not over 25 ºС.

Issue conditions:

Without recipe

Packaging:

On 10 tablets in the blister. On 2 or 5 blisters in a pack.