Betalok of 1 mg/ml

General characteristics. Structure:

Active agent: 1 mg of a metoprolol of tartrate for injections
Excipients: sodium chloride for injections of 9 mg, water for injections to 1 ml.

Description. Transparent, colourless liquid.

Pharmacological properties:

Pharmacodynamics. At patients with a myocardial infarction intravenous administration of a metoprolol reduces a stethalgia and reduces risk of development of blinking and an atrial flutter. Intravenous administration of a metoprolol at the first symptoms (within 24 hours after emergence of the first symptoms) reduces risk of development of a myocardial infarction. The early initiation of treatment metoprololy leads to improvement of the further forecast of treatment of a myocardial infarction.

Reduction of the heart rate (HR) at a Bouveret's disease and blinking (trembling) of auricles is reached. Metoprolol-β1-адреноблокатор, blocking β1-рецепторы in doses considerably smaller, than the doses which are required for blocking β2-receptors. Metoprolol possesses insignificant membrane stabilizing action and does not show activity of a partial agonist. Metoprolol reduces or inhibits agonistic action. which render the catecholamines which are formed at nervous and physical stresses on cordial activity. It means what метопролол has ability to interfere with increase in heart rate, minute volume and strengthening of contractility of a myocardium, and also rise in the arterial pressure (AP), the catecholamines caused by sharp emission. Patients with symptoms of obstructive diseases of lungs if necessary can appoint метопролол in combination with β2-адреномиметиками. When sharing with β2-adrenomimetikam Betalok, in therapeutic doses, to a lesser extent influences the bronkhodilatation, than non-selective β-adrenoblockers caused β2-by adrenomimetika..........

Metoprolol to a lesser extent, than non-selective β-adrenoblockers, influences products of insulin and carbohydrate metabolism. Drug influence Betalok on reaction of cardiovascular system in the conditions of a hypoglycemia is considerably less expressed in comparison with non-selective β-adrenoblockers.......... Improvement of quality of life at treatment by drug Betalok was observed at patients after a myocardial infarction.

Pharmacokinetics. Metoprolol is exposed to oxidizing metabolism in a liver with formation of three main metabolites, any of which has no clinically significant β-the blocking effect. About 5% of the accepted dose are removed with urine in not changed look. The average elimination half-life of a metoprolol makes about 3 - 5 hours of a blood plasma.

Indications to use:

Supraventricular tachycardia. Prevention and treatment of ischemia of a myocardium, tachycardia and pain at a myocardial infarction or suspicion on it.

Route of administration and doses:

Supraventricular tachycardia
Begin introduction with 5 mg (5 ml) of drug Betalok with a speed of 1-2 mg/min. It is possible to repeat introduction with the 5th minute interval before achievement of therapeutic effect. Usually total dose makes 10-15 mg (10-15 ml). The recommended maximum dose at intravenous administration makes 20 mg (20 ml).
Prevention and treatment of ischemia of a myocardium, tachycardia and pain at a myocardial infarction or suspicion on it
Intravenously 5 mg (5 ml) of drug. It is possible to repeat introduction with the 2nd minute interval, the maximum dose - 15 mg (15 ml). In 15 minutes after the last injection 50 mg (Betalok) each 6 hours within 48 hours appoint метопролол for intake in a dose.
Renal failure
There is no need to adjust doses at patients with a renal failure.
Abnormal liver function
Usually because of low extent of communication with proteins of plasma, dose adjustment it is not required. However, at a heavy abnormal liver function (at patients with porto-caval an anastomosis) the dose decline can be required.
Advanced age
There is no need to adjust doses at patients of advanced age.
Children
Experience of use of drug Betalok at children is limited.

Features of use:

To the patients accepting β-adrenoblockers, it is not necessary to enter intravenously blockers of "slow" calcium channels like verapamil. To the patients having bronchial asthma or an obstructive disease of lungs. the accompanying bronkhodilatiruyushchy therapy has to be appointed. In case of need it is necessary to increase a dose β2-адреномиметика. When using β1-адреноблокаторов the risk of their influence on carbohydrate metabolism or a possibility of masking of a hypoglycemia is much less, than when using non-selective β-adrenoblockers..........

With chronic heart failure in a stage of a decompensation it is necessary to achieve a stage of compensation from patients both to, and during treatment by drug. The patients having Printsmetal's stenocardia are not recommended to appoint non-selective β-adrenoblockers..........

Very seldom at patients with disturbance of atrioventricular conductivity there can occur deterioration (a possible outcome an atrioventricular block). If against the background of treatment bradycardia developed, Betalok's dose needs to be reduced. Metoprolol can worsen symptoms of disturbance of peripheric arterial circulation generally owing to a lowering of arterial pressure. It is necessary to show care at purpose of drug to the patients having a heavy renal failure at a metabolic acidosis, joint appointment with cordial glikofzida. At the patients accepting β-adrenoblockers, the acute anaphylaxis proceeds in more severe form. The patients suffering from a pheochromocytoma in parallel with drug Betalok should appoint alpha adrenoblocker. In case of surgical intervention it is necessary to inform the anesthesiologist that the patient accepts β-adrenoblocker.......... It is not necessary to appoint a repeated dose - the second or third at heart rate less than 40 beats per minute, PQ interval more than 0,26 seconds and with a systolic arterial pressure less than 90 mm hg.

Side effects:

Betalok is well had by patients, and side effects generally are easy and reversible.
As a result of clinical trials or at drug use Betalok (a metoprolola tartrate) in clinical practice the following undesirable side effects were described. In many cases, relationship of cause and effect drug Betalok was not established with treatment. Applied the following criteria to assessment of frequency of cases:
very often (> 10%), it is frequent (1-9,9%), infrequently (0,1-0,9%), is rare (0,01-0,09%) and is very rare (<0,01%).
From cardiovascular system
Often: the bradycardia, postural disturbances (which are very seldom followed by a faint), feeling of a cold snap of extremities, a heart consciousness.
Infrequently: temporary strengthening of symptoms of heart failure, cardiogenic shock at patients with an acute myocardial infarction, an atrioventricular block of the I degree, hypostases, pains in heart.
Seldom: other disturbances of conductivity, arrhythmia.
Very seldom: gangrene at patients with the previous heavy disturbances of peripheric circulation.
From the central nervous system
Very often: increased fatigue.
Often: dizziness, headache.
Infrequently: paresthesias, spasms, aggravation of a course of a depression, decrease in concentration of attention, drowsiness or sleeplessness, nightmares.
Seldom: hypererethism, uneasiness.
Very seldom: memory amnesia/disturbance, condition of depression, hallucination.
From the alimentary system
Often: nausea, pains in a stomach, diarrhea, a lock.
Infrequently: vomiting.
Seldom: dryness of a mucous membrane of an oral cavity, abnormal liver function.
Very seldom: hepatitis.
From skin and hypodermic fabrics
Infrequently: rash (in the form of a small tortoiseshell), the increased sweating.
Seldom: alopecia.
Very seldom: photosensitization, aggravation of a course of psoriasis.
From respiratory system
Often: an asthma at loading.
Infrequently: a bronchospasm at patients with bronchial asthma.
Seldom: rhinitis.
From sense bodys
Seldom: vision disorders, dryness and/or irritation of eyes, conjunctivitis.
Very seldom: a ring in ears, disturbances of flavoring feelings.
From a metabolism
Infrequently: increase in body weight.
From skeletal and muscular system
Very seldom: arthralgia.
From blood
Very seldom: thrombocytopenia.
Others
Seldom: impotence / sexual dysfunction.

Interaction with other medicines:

It is necessary to avoid joint purpose of drug Betalok with the following drugs:

Derivatives of barbituric acid: barbiturates (the research was conducted with phenobarbital) slightly strengthen metabolism of a metoprolol, owing to induction of enzymes.

Propafenon: at purpose of a propafenon to four patients receiving treatment metoprololy increase in plasma concentration of a metoprolol by 2-5 times was noted, at the same time at two patients the side effects characteristic of a metoprolol were noted. This interaction was confirmed during the research on 8 volunteers. Possibly, interaction is caused by inhibition propafenony, like quinidine, metabolism of a metoprolol by means of system of P4502D6 cytochrome. In view of the fact that пропафенон has properties of β-adrenoblocker, joint purpose of a metoprolol and a propafenona is not advisable.

Verepamil: the combination of β-adrenoblockers ((((((((((an atenolola, propranolol and Pindololum) and verapamil can cause bradycardia and lead to decrease in the ABP. Verapamil and β-adrenoblockers have the complementary inhibiting effect on atrioventricular conductivity and function of a sinus node.

The drug combination Betalok with the following drugs can demand dose adjustment:

Antiarrhytmic means of the I class: Antiarrhytmic means of the I class and β-adrenoblockers can lead to summing of a negative inotropic effect which can result in serious hemodynamic side effects at patients with the broken function of a left ventricle. Also it is necessary to avoid a similar combination at patients with a sick sinus syndrome and disturbance of atrioventricular conductivity. Interaction is described on the example of Disopyramidum.

Amiodaronum: Combined use of Amiodaronum and metoprolol can lead to the expressed sinus bradycardia. In view of extremely long elimination half-life of Amiodaronum (50 days), it is necessary to consider possible interaction later long time after cancellation of Amiodaronum.

Diltiazem: Diltiazem and β-adrenoblockers mutually strengthen the inhibiting effect on atrioventricular conductivity and function of a sinus node. At a combination of a metoprolol with diltiazem cases of the expressed bradycardia were noted.

Non-steroidal anti-inflammatory drugs (NPVP): NPVP weaken anti-hypertensive effect of β-adrenoblockers.......... This interaction is most documented for indometacin. The described interaction for a sulindak is noted. In researches with diclofenac of the described reaction it was not noted.

Difengidramin: Difengidramin reduces clearance of a metoprolol to α-a gidroksimetoprolola by 2,5 times. Strengthening of action of a metoprolol is at the same time observed.

Epinephrinum (adrenaline): It was reported about 10 cases of the expressed arterial hypertension and bradycardia at the patients who were accepting non-selective β-adrenoblockers (including Pindololum and пропраполол) and receiving Epinephrinum (adrenaline). Interaction is noted also in group of healthy volunteers. It is supposed that similar reactions can be observed also at use of Epinephrinum together with local anesthetics at accidental hit in a vascular bed. It is supposed that this risk is much lower at use of cardioselective β-adrenoblockers..........

Fenilpropanolamin: Fenilpropanolamin (норэфедрин) in a single dose of 50 mg can cause increase in the diastolic ABP to pathological values in healthy volunteers. Propranolol generally interferes with the increase in the ABP caused fenilpropanolaminy. However, β-adrenoblockers can cause reactions of paradoxical arterial hypertension in the patients receiving high doses of a fenilpropanolamin. It was reported about several cases of development of hypertensive crisis against the background of reception of a fenilpropanolamin.

Quinidine: Quinidine inhibits metabolism of a metoprolol at special group of patients with a bystry hydroxylation (in Sweden about 90% of the population), causing, mainly, significant increase in plasma concentration of a metoprolol and strengthening of β-blockade. Believe that similar interaction is characteristic and for which other β-adrenoblockers P4502D6 cytochrome participates in metabolism.

Clonidine: Hypertensive reactions at sharp cancellation of a clonidine can amplify at joint reception of β-adrenoblockers.......... At combined use, in case of cancellation of a clonidine, the termination of reception of β-adrenoblockers should be begun some days before cancellation of a clonidine.

Rifampicin: Rifampicin can strengthen metabolism of a metoprolol, reducing plasma concentration of a metoprolol. Concentration of a metoprolol in a blood plasma can increase at the combined use with Cimetidinum, gidralaziny, the selection inhibitors of serotonin, such as пароксетин, fluoxetine and sertraline. The patients who are at the same time accepting метопролол and other β-adrenoblockers ((((((((((eye drops) or inhibitors of a monoaminooxidase (MAO), have to be under careful observation. Pases a background of reception of β-adrenoblockers inhalation anesthetics strengthen cardiodepressive action. Against the background of reception of β-adrenoblockers dose adjustment of the last can be required by the patients receiving peroral hypoglycemic means.
Cardiac glycosides at combined use with β-adrenoblockers can increase time of atrioventricular conductivity and cause bradycardia.

Contraindications:

Atrioventricular block of II and III degrees, heart failure in a decompensation stage, clinically significant sinus bradycardia, a sick sinus syndrome, cardiogenic shock, the expressed disturbances of peripheric circulation, arterial hypotension.

Metoprolol is contraindicated to patients with an acute myocardial infarction at ChSS less than 45 beats per minute, PQ interval more than 0,24 seconds or with a systolic arterial pressure less than 100 mm hg.

The known hypersensitivity to a metoprolol and its components or to other β-adrsnoblokator.

At serious peripheral vascular diseases at threat of gangrene.

At treatment of supraventricular tachycardia at patients with systolic arterial pressure less than 110 mm hg.

To the patients receiving β-adrenoblockers, contraindicated intravenous administration of blockers of "slow" calcium channels like verapamil.

Age up to 18 years (efficiency and safety are not established)

With care: atrioventricular block of the I degree, Printsmetal's stenocardia, chronic obstructive pulmonary disease (emphysema of lungs, chronic obstructive bronchitis, bronchial asthma), diabetes mellitus, heavy renal failure.

Use at pregnancy and in the period of a lactation

Pregnancy
As well as the majority of drugs, Betalok it is not necessary to appoint during pregnancy and during chest feeding unless the expected advantage for mother exceeds potential risk for a fruit. As well as other anti-hypertensive means, β-adrenoblockers can cause side effects, for example, bradycardia in a fruit, the newborns or children who are on breastfeeding in this connection it is necessary to be especially careful at purpose of β-adrenoblockers in the last trimester of pregnancy and just before childbirth.

Lactation period
The quantity of a metoprolol which is marked out in breast milk, and β-the blocking action at the child who is on breastfeeding (at reception by mother of a metoprolol in therapeutic doses), are insignificant.

Overdose:

Toxicity
Metoprolol in a dose of 7,5 g caused intoxication with a lethal outcome in the adult. At 5 summer children who accepted 100 mg of a metoprolol after a gastric lavage symptoms of intoxication were not noted. Reception of 450 mg of a metoprolol by the teenager of 12 years led to moderate intoxication. Reception of 1,4 g and 2,5 g of a metoprolol by adults caused moderate and heavy intoxication, respectively. Reception of 7,5 g adult led to extremely heavy intoxication.

Symptoms
At overdose metoprololy the most serious are symptoms from cordial vascular system, however sometimes, especially at children and teenagers, symptoms from TsNS can prevail and suppression of pulmonary function. Bradycardia, an atrioventricular block of I-Sh of degree, an asystolia, the expressed decrease in the ABP, weak peripheral perfusion, heart failure, cardiogenic shock. Oppression of function of lungs, apnoea. And also, the increased fatigue, consciousness disturbance, a loss of consciousness, a tremor, spasms, the increased sweating, paresthesias, a bronchospasm, nausea, vomiting, the ezofagialny spasm, a hypoglycemia (especially at children) or a hyperglycemia, a hyperpotassemia is possible. Impact on kidneys. Tranzitorny myasthenic syndrome. The accompanying alcohol intake, anti-hypertensive drugs, quinidine or barbiturates can worsen a condition of the patient.
The first signs of overdose can be observed in 20 min. - 2 hours after administration of drug.

Treatment
Purpose of absorbent carbon, in case of need gastric lavage.
IMPORTANT! Atropine (0,25-0,5 mg in/in for adults, 10-20 mkg/kg for children) has to be appointed to a gastric lavage (because of risk of stimulation of a vagus nerve). If necessary maintenance of passability of respiratory tracts (intubation) and adequate ventilation of the lungs. Completion of volume of the circulating blood and infusion of glucose. Control of an ECG. Atropine of 1,0-2,0 mg in/in, if necessary repeat introduction (especially in case of vagal symptoms). In case of (suppression) of a depression of a myocardium infusional introduction of Dobutaminum or dopamii is shown. It is also possible to apply a glucagon of 50 - 150 mkg/kg in/in at an interval of 1 minute. Addition to adrenaline therapy can be in certain cases effective. At arrhythmia and increase in a ventricular complex (QRS) infusionally enter sodium solutions (chloride or bicarbonate). Installation of an artificial pacemaker is possible. At a cardiac standstill owing to overdose resuscitation actions within several hours can be necessary. To stopping of a bronchospasm it can be applied тербуталин (injektsionno or by means of inhalations). The symptomatic treatment is carried out.

Storage conditions:

In the place protected from light, at a temperature below 25 °C. To store in the place, unavailable to children. Period of validity of 5 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Solution for intravenous administration of 1 mg/ml. On 5 ml in ampoules from colourless borosilicate glass with a notch. 5 ampoules in the plastic fixer in a cardboard pack with the application instruction.