Betalok of 100 mg

General characteristics. Structure:

Active agent: one tablet contains 100 mg of a metoprolol of tartrate.
Excipients: lactoses monohydrate, magnesium stearate, cellulose microcrystallic, carboxymethylstarch of sodium, silicon dioxide colloid anhydrous, povidone.
Description
Biconvex tablets of a round form, white color with risky and an engraving of A on one party.
mE

Pharmacological properties:

Metoprolol - β1-адреноблокатор, blocking β1-рецепторы in doses considerably smaller, than the doses which are required for blocking β2-рецепторов. Metoprolol has insignificant membrane stabilizing effect and does not show activity of a partial agonist. Metoprolol reduces or inhibits agonistic effect which the catecholamines which are allocated at nervous and physical stresses have on cordial activity. It means what метопролол has ability to interfere with increase in the heart rate (HR), minute volume and strengthening of contractility of heart, and also increase in the arterial pressure (AP), the catecholamines caused by sharp emission.

Pharmacodynamics. 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..........
Clinical trials showed that Betalok can cause slight increase of level of triglycerides and reduction of content of free fatty acids in blood. Insignificant reduction of fraction of lipoproteins of the high density (LPVP) was in certain cases noted that is less expressed, than in case of use of non-selective β-adrenoblockers.......... However in one of clinical trials considerable decrease in level of the general cholesterol in blood serum at treatment was shown metoprololy within several years.
Quality of life during treatment by drug Betalok does not worsen or improves. Improvement of quality of life at treatment by drug Betalok was observed at patients after a myocardial infarction.

Pharmacokinetics. Metoprolol is almost completely absorbed after intake. At administration of drug within therapeutic doses concentration of drug in a blood plasma is in linear dependence on the accepted dose. The maximum concentration in a blood plasma is reached in 1,5 - 2 hours after administration of drug.
After intake of the first dose of a metoprolol of system blood circulation reaches about 50% of a dose. At repeated receptions the indicator of system bioavailability increases up to 70%. Administration of drug together with food can increase system bioavailability for 30-40%. Communication with proteins of a blood plasma of low, about 5-10%.
Metabolism and removal
Metoprolol is exposed to oxidizing metabolism in a liver with formation of 3 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, in some cases this indicator can reach 30%.
The average elimination half-life of a metoprolol makes about 3,5 hours of a blood plasma (minimum - 1 hour, as much as possible - 9 hours). The plasma clearance makes about 1 l/min.
At patients of advanced age considerable changes in pharmacokinetics of a metoprolol in comparison with patients of young age are not observed.
System bioavailability and removal of a metoprolol does not change at patients with reduced function of kidneys. Removal of metabolites at such patients, however, is reduced. Considerable accumulation of metabolites was observed at patients with a glomerular filtration rate less than 5 ml/min. However, such accumulation of metabolites does not strengthen the β-blocking effect.
At patients with reduced function of a liver the pharmacokinetics of a metoprolol (in connection with the low level of communication with proteins) changes slightly. However at patients with a severe form of cirrhosis or a porto-caval anastomosis, bioavailability of a metoprolol can increase, and the general clearance to decrease. At patients with a porto-caval anastomosis the general clearance made about 300 ml/min., and the area under a curve concentration in a blood plasma – time (AUC) was in 6 times more in comparison with a similar indicator at healthy patients.

Indications to use:

• Arterial hypertension: a lowering of arterial pressure and reduction of risk of cardiovascular and coronary death (including sudden death).
• Stenocardia.
• Disturbances of a heart rhythm, including supraventricular tachycardia.
• In complex therapy after a myocardial infarction.
• The functional disturbances of cordial activity which are followed by tachycardia.
• Prevention of attacks of migraine.
• Hyperthyroidism (complex therapy).

Route of administration and doses:

Pill can be taken as together with food, and on an empty stomach.
Arterial hypertension
100-200 mg of drug Betalok once in the morning or in two steps; in the morning and in the evening. If necessary the dose can be increased or added other anti-hypertensive means.
Long anti-hypertensive therapy of 100-200 mg of drug Betalok in days allows to reduce the general mortality, including sudden death, and also frequency of developing of brain strokes and disturbances of coronary circulation at patients with arterial hypertension.
Stenocardia
100-200 mg a day in two steps; in the morning and in the evening. If necessary other anti-anginal drug can be added to therapy.
Disturbances of a heart rhythm
100-200 mg a day in two steps; in the morning and in the evening. If necessary other antiarrhytmic drug can be added to therapy.
Maintenance therapy after a myocardial infarction
The maintenance dose makes 200 mg a day in two steps; in the morning and in the evening. Betalok's appointment in a dose of 200 mg a day allows to reduce mortality at the patients who had a myocardial infarction and to reduce risk of development of a repeated myocardial infarction (including at patients with a diabetes mellitus).
The functional disturbances of cordial activity which are followed by tachycardia
100 mg of drug Betalok once a day, is recommended to take a pill in the morning. If necessary the dose can be increased.
Prevention of attacks of migraine
100-200 mg a day in two steps; in the morning and in the evening.
Hyperthyroidism
150-200 mg a day in 3-4 receptions.
Renal failure
There is no need to adjust a dose at patients with a renal failure.
Abnormal liver function
Usually because of low extent of communication with proteins of plasma dose adjustment of a metoprolol is not required. However at a heavy abnormal liver function (at patients with
severe form of cirrhosis or porto-caval anastomosis) the dose decline can be required.
Advanced age
There is no need to adjust a dose 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.
The patients having an obstructive pulmonary disease are not recommended to appoint β-adrenoblockers.......... In case of bad portability of other anti-hypertensive means or their inefficiency, it is possible to appoint метопролол as it is the selection drug. It is necessary to appoint minimum effective dose, if necessary appointment β2-адреномиметика is possible.
When using β1-адреноблокаторов the risk of their influence on carbohydrate metabolism or a possibility of masking of symptoms 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 AV of conductivity there can occur deterioration (a possible outcome – AV blockade). If against the background of treatment bradycardia developed, Betalok's dose needs to be reduced or it is necessary to cancel drug gradually.
Metoprolol can worsen symptoms of disturbance of peripheric 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 cardiac glycosides.
The patients suffering from a pheochromocytoma in parallel with drug Betalok should appoint alpha adrenoblocker.
At patients with cirrhosis bioavailability of a metoprolol increases.
In case of surgical intervention it is necessary to inform the anesthesiologist that the patient accepts β-adrenoblocker..........
It is necessary to avoid sharp drug withdrawal. In need of drug withdrawal, cancellation should be carried out gradually. At most of patients administration of drug can be cancelled in 14 days. The dose of drug is reduced gradually, in stages, to achievement of a final dose of 25 mg once a day. Patients with coronary heart disease have to be under careful observation of the doctor during drug withdrawal. At patients,
accepting β-adrenoblockers, the acute anaphylaxis proceeds in more severe form.
Influence on ability to drive the car and to work with technical devices
At use of drug episodes of dizziness or the general weakness in this connection it is necessary 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 are possible.

Side effects:

Betalok is well had by patients, side effects generally are easy and reversible.
As a result of clinical trials or at drug use Betalok (метопролол tartrate) in clinical practice the following undesirable side effects were described. In many cases relationship of cause and effect Betalok was not established with administration of drug. 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%).
Cardiovascular system
Often: the bradycardia, postural disturbances (which are very seldom followed by a faint), a cold snap of extremities, heartbeat;
Infrequently: temporary strengthening of symptoms of heart failure, AV blockade of the I degree; cardiogenic shock at patients with an acute myocardial infarction;
Seldom: other disturbances of cordial conductivity, arrhythmia;
Very seldom: gangrene at patients with the previous heavy disturbances of peripheric circulation.
Central nervous system
Very often: increased fatigue;
Often: dizziness, headache;
Infrequently: paresthesias, spasms, depression, easing of attention, drowsiness or sleeplessness, nightmares;
Seldom: the increased nervous irritability, uneasiness, impotence / sexual dysfunction;
Very seldom: memory amnesia/disturbance, depression, hallucinations.
Digestive tract
Often: nausea, pains in a stomach, diarrhea, a lock;
Infrequently: vomiting;
Seldom: dryness in a mouth.
Liver
Seldom: abnormal liver functions;
Very seldom: hepatitis.
Integuments
Not often: rash (in the form of a small tortoiseshell), the increased perspiration;
Seldom: hair loss;
Very seldom: photosensitization, exacerbation of psoriasis.
Respiratory organs
Often: an asthma at physical effort;
Infrequently: bronchospasm;
Seldom: rhinitis.
Sense bodys
Seldom: vision disorders, dryness and/or irritation of eyes, conjunctivitis;
Very seldom: a ring in ears, disturbances of flavoring feelings.
From skeletal and muscular system:
Very seldom: arthralgia
Metabolism
Infrequently: increase in body weight.
Blood
Very seldom: thrombocytopenia.

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 fenofarbitaly) 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.
Verapamil: 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 AV of 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 AV 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: дифенгидрамин reduces clearance of a metoprolol to a α-gidroksimetoprolol 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 propranolol) 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..........
енилпропаноламин: фенилпропаноламин (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. Against the 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, the patients receiving long or intermittent therapy by inotropic means and acting on beta adrenoceptors, clinically significant sinus bradycardia, a sick sinus syndrome, cardiogenic shock, the expressed disturbances of peripheric circulation, arterial hypotension.
Betalok 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-adrenoblockers..........
At serious peripheral vascular diseases at threat of gangrene.
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 during pregnancy and chest feeding
As well as Betalok it is not necessary to appoint the majority of drugs during pregnancy and during chest feeding unless the expected advantage for mother exceeds potential risk for a fruit and/or the child. 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.
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:

Symptoms
Betalok the expressed decrease in the ABP, a sinus bradycardia, an atrioventricular block, heart failure, cardiogenic shock, a cardiac standstill, a bronchospasm, disturbance of a consciousness/lump, nausea, vomiting and cyanosis can be drug overdose effects.
The accompanying alcohol intake, reception of anti-hypertensive means, quinidine or barbiturates can lead to an aggravation of symptoms of the patient.
The first signs of overdose can be shown within 20 one or 2nd minutes of hours after administration of drug.
Treatment
To accept absorbent carbon, if necessary a gastric lavage. In case of the expressed decrease in the ABP, bradycardia or threat of heart failure it is necessary to enter β1-адреномиметик (for example, Dobutaminum) intravenously with an interval of 2-5 minutes or infusionally before achievement of therapeutic effect. In case of unavailability of the selection β1-агониста it is possible to enter intravenously a dopamine or atropine sulfate for blockade of a vagus nerve.
If the therapeutic effect is not reached, it is possible to use other sympathomimetics, such as Dobutaminum or noradrenaline.
It is possible to enter a glucagon in a dose of 1-10 mg. There can sometimes be a need of use of the driver of a cordial rhythm. For stopping of a bronchospasm it is necessary to enter intravenously β2-адреномиметик.
It is necessary to consider that the doses of antidotes necessary for elimination of the symptoms arising at overdose of β-adrenoblockers, are much higher therapeutic as β-adrenoceptors are in the connected state with β-adrenoblocker..........

Storage conditions:

At a temperature not above 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:

Tablets on 100 mg. On 100 tablets in a plastic bottle with the screwing-up plastic cover with control of the first opening, 1 bottle is placed in a cardboard pack with the application instruction.