Betaksolol

General characteristics. Structure:

Active ingredient: 20 mg of a betaksolol of a hydrochloride.

Excipients: lactoses monohydrate (sugar milk), microcrystallic cellulose, magnesium stearate, sodium carboxymethylstarch (примогель), aerosil (silicon dioxide colloid).

Film cover: опадрай the II white 85F18422 [polyvinyl alcohol, titanium dioxide, macrogoal (polyethyleneglycol).

Pharmacological properties:

Pharmacodynamics. Betaksolol is characterized by three pharmacological properties:

- cardioselective β-adrenoceptor blocking action;

- lack of partial agonistic activity (that is does not show own sympathomimetic action);

- weak membrane stabilizing effect (like quinidine or local anesthetics) in the concentration exceeding therapeutic.

The selection influence of a betaksolol on β1-адренорецепторы is not absolute, so at its use in high doses influence of a betaksolol on β2-адренорецепторы, located, mainly, in smooth muscles of bronchial tubes and vessels (however influence of a betaksolol on β2-адренорецепторы is much weaker than that at non-selective β-adrenoblockers) is possible))))))))).

At use of a betaksolol it the activity blocking β1-адренорецепторы is shown by the following pharmakodinamichesky effects:

- reduction of number of cordial reductions in rest and at an exercise stress (due to blockade of β-adrenoceptors in a sinus node that in combination with absence at a betaksolol of internal sympathomimetic activity leads to delay of automatism of a sinus node);

- decrease cordial, emission at rest and at an exercise stress at the expense of competitive antagonism with catecholamines in peripheral (especially cardial) adrenergic nerve terminations;

- decrease in systolic and diastolic arterial pressure at rest and at an exercise stress (the mechanism of hypotensive action is described below);

- reduction of a reflex of orthostatic tachycardia.

These effects are resulted by reduction of load of heart at rest and at an exercise stress. The mechanism of hypotensive effect of β-adrenoblockers is completely not installed.

At β-adrenoblockers the following mechanisms of hypotensive action are assumed:

- decrease in cordial emission;

- elimination of a spasm of peripheral arteries (due to the central action leading to decrease in a sympathetic impulsation on the periphery to vessels, and at the expense of inhibition of activity of a renin).

Hypotensive action of a betaksolol at its long reception does not decrease. At a single dose of a betaksolol within a day (from 5 to 40 mg) hypotensive action is identical in 3-4 hours (time of achievement of Cmax of a betaksolol in blood) and in 24 hours (before reception of the next dose).

At reception of 5 mg and 10 mg of a betaksolol its hypotensive action makes, respectively, 50% and 80% of hypotensive action at reception of 20 mg of a betaksolol. Thus, in the range of doses of 5-20 mg the dozozavisimost of hypotensive effect is observed, and at increase in a dose from 10 mg to 20 mg the gain of hypotensive effect is insignificant. Increase in a dose from 20 mg to 40 mg changes hypotensive action of a betaksolol a little. The maximum hypotensive effect of each dose of a betaksolol is reached in 1-2 weeks.

Unlike hypotensive action of a betaksolol the effect of reduction of number of cordial reductions at increase in its dose (from 10 mg to 40 mg) does not increase.

Besides, бетаксолол it is capable to slow down conductivity of an atrioventricular node.

Pharmacokinetics. Absorption. Betaksolol quickly and completely (100%) is absorbed from digestive tract after intake, bioavailability - about 85%. The maximum concentration in a blood plasma are reached in 2-4 hours. Betaksolol contacts proteins of a blood plasma approximately for 50%.

Permeability through a blood-brain and placental barrier - low. Secretion with breast milk - insignificant.

Metabolism. Distribution volume - about 6 l/kg. Betaksolol is metabolized in a liver with formation of inactive metabolites. Solubility in fats moderate.

Removal. 10-15% in not changed look are removed by kidneys in the form of metabolites (more than 80%). The elimination half-life (T1/2) of a betaksolol makes 15-20 hours. T1/2 at an abnormal liver function is extended for 33%, but the clearance does not change; at a renal failure of T1/2 doubles (decrease in doses is necessary).

Is not removed at a hemodialysis.

Indications to use:

- arterial hypertension;

- prevention of attacks of an angina of exertion.

Route of administration and doses:

Betaksolol to accept drug inside, not to chew, wash down with enough liquid.

The initial dose of drug of Betaksolol according to both indications makes 10 mg/days (1/2 tablets of 20 mg), a maintenance dose - 20 mg/days.

Dosage at patients with renal and/or with a liver failure

With a slight and moderate renal failure and/or with a liver failure of correction of an initial dose it is not required to patients, however, in an initiation of treatment regular medical observation is necessary.

To patients with a heavy renal failure (clearance of creatinine less than 20 ml/min.) the recommended initial dose should not exceed 10 mg. The maximum daily dose of drug makes 20 mg.

Features of use:

Pregnancy and lactation. Teratogenecity. Teratogenic effect of drug in experiments on animals was not revealed. So far at people teratogenic effects are noted, and controlled prospective researches did not reveal inborn uglinesses.

Use at pregnancy is possible only in that case when the advantage for mother exceeds potential risk for a fruit and/or the child.

Breastfeeding. β-adrenoblockers get into breast milk (see. "Pharmacokinetics").

The risk of a hypoglycemia or bradycardia was not investigated therefore breastfeeding during treatment needs to be stopped.

Treatment of patients with stenocardia never should be interrupted sharply: sudden cancellation can lead to heavy disturbances of a cordial rhythm, a myocardial infarction or sudden death. The dose should be reduced gradually, that is, within 1-2 weeks, and in case of need it is possible to begin at the same time replacement therapy to avoid progressing of a disease.

It is necessary to carry out control of the patients accepting Betaksolol, it has to include observation of number of cordial reductions and arterial pressure (in an initiation of treatment daily, then 1 time in 3-4 months), concentration of glucose in blood at patients with a diabetes mellitus (1 time in 4-5 months), control of function of kidneys at elderly patients is necessary (1 time in 4-5 months).

It is necessary to train the patient in a technique of calculation of number of cordial reductions and to instruct about need of medical consultation at number of cordial reductions less than 50 blows/min.

Approximately at 20% of patients stenocardia β-adrenoblockers are inefficient. The main reasons - heavy coronary atherosclerosis with a low threshold of ischemia (number of cordial reductions at the time of development of an anginal attack less than 100 blows/min.) and the increased final diastolic pressure of a left ventricle breaking a subendocardial blood stream.

At a concomitant use of a clonidine its reception can be stopped only in several days after Betaksolol's cancellation.

Betaksolol it is necessary to cancel before a research of content in blood and urine of catecholamines, a normetanefrin and vanilinmindalny acid; credits of antinuclear antibodies.

Bronchial asthma and chronic obstructive pulmonary disease. β-adrenoblockers can be appointed only to patients with moderate severity of a disease, with the choice of the selection β-adrenoblocker in a low initial dose. Before an initiation of treatment it is recommended to carry out breath function assessment. At development of attacks during treatment bronchodilators - β2-адреномиметики can be applied.

Heart failure. At patients with controlled heart failure, in case of need Betaksolol can be applied in very low, gradually increasing doses, under strict medical observation.

Bradycardia. The dose needs to be reduced if the number of cordial reductions are at rest lower than 50-55 blows/min. and the patient has clinical displays of bradycardia. Atrioventricular block of the I degree

Considering negative dromotropic effect of β-adrenoblockers, at blockade of the I degree drug should be used with care.

Printsmetal's stenocardia. β-adrenoblockers can increase number and duration of attacks at the patients having Printsmetal's stenocardia. Use cardioselective β1-адреноблокаторов is possible at less heavy and mixed forms provided that treatment is carried out in combination with vazodilatator.

Disturbances of peripheric circulation. β-adrenoblockers can lead to an aggravation of symptoms of patients with disturbances of peripheric circulation (a Raynaud's disease or Reynaud's syndrome, arteritis or chronic obliterating diseases of arteries of the lower extremities).

Pheochromocytoma. In case of use of β-adrenoblockers at treatment of the arterial hypertension caused by a pheochromocytoma careful control of arterial pressure is required.

Elderly patients. Treatment of elderly patients should be begun with the lowest and well tolerable dose and under strict observation.

Patients with a renal failure. The dose needs to be adjusted depending on concentration of creatinine in blood or clearance of creatinine (see. "Route of administration and doses").

Patients with a diabetes mellitus. It is necessary to warn the patient about need to strengthen self-checking of concentration of glucose in blood in an initiation of treatment. Initial symptoms of a hypoglycemia can be disguised, especially tachycardia, heartbeat and perspiration.

Psoriasis. Careful assessment of need of purpose of drug as there are messages on an aggravation of symptoms during treatment by β-adrenoblockers is required..........

Allergic reactions. At the patients inclined to the heavy anaphylactic reactions in particular connected using a floktafenin or when performing desensitization therapy by β-adrenoblockers can lead to further strengthening of reactions and decrease in efficiency of therapy.

General anesthesia. β-adrenoblockers disguise reflex tachycardia and increase risk of development of arterial hypotension. Therapy continuation by β-adrenoblockers reduces risk of development of arrhythmia, ischemia of a myocardium and hypertensive crises. The anesthesiologist should report that the patient received treatment by β-adrenoblockers..........

- If the termination of treatment is recognized necessary, then it is considered that the termination of therapy for 48 hours allows to recover sensitivity to catecholamines.

- Therapy by β-adrenoblockers should not be interrupted in the following cases:

• at patients with coronary insufficiency it is desirable to continue therapy up to surgical intervention, considering the risk connected with sudden cancellation of β-adrenoblockers;;;;;;;;;;
• in case of the emergency surgical interventions or when the termination of therapy is impossible, the patient should be protected from effects of excitement of a vagus nerve by the corresponding premedication atropine, with repetition in case of need. For the general anesthesia it is necessary to use the medicines which are least oppressing a myocardium.

- The risk of development of anaphylactic reactions has to be considered.

Thyrotoxicosis. Symptoms of a thyrotoxicosis can mask at therapy by β-adrenoblockers..........

Athletes. Athletes have to consider that drug contains active ingredient which can give positive reaction when carrying out tests of doping control.

For the period of treatment to exclude the ethanol use.

The patients using contact lenses have to consider that against the background of treatment reduction of the lacrimal liquid is possible.

At tobacco smoking efficiency of β-adrenoblockers is lower.

At newborns whose mothers were treated by β-adrenoblockers, action of the last remains for several days after the birth. Though this residual effect can not have clinical effects, nevertheless development of the heart disease demanding an intensive care of the newborn is possible (see. "Overdose"). In such situation it is necessary to avoid administration of the solutions (risk of development of an acute fluid lungs) increasing the volume of blood. Also there are messages on bradycardia, respiratory a distress syndrome and a hypoglycemia. Therefore careful observation of newborns in specialized conditions is recommended (control of number of cordial reductions and concentration of glucose in blood during the first 3-5 days of life).

Influence on ability to manage vehicles and mechanisms. During treatment it is necessary to be careful at control of vehicles and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

The WHO classification of undesirable side reactions on development frequency: very frequent  - 1/10 appointments (≥10%); frequent  - 1/100 appointments (≥1%, but <10%); infrequent  - 1/1000 appointments (≥ 0,1%, but <1%); rare  - 1/10000 appointments (≥0,01%, but <0,1%); very rare  - less than 1/10000 appointments (<0,01%).

From the central nervous system: often - increased fatigue, weakness, dizziness, a headache, drowsiness or sleeplessness, nightmares; seldom - a depression; very seldom - concern, confusion of consciousness or short-term loss of memory, a hallucination, an asthenic syndrome, muscular weakness, paresthesias in extremities (at patients with the "alternating" lameness, Reynaud's syndrome), a tremor.

From cardiovascular system: often - a sinus bradycardia, a heart consciousness, orthostatic hypotension, disturbance of conductivity of a myocardium, an atrioventricular block (up to a cardiac standstill), arrhythmias, easing of contractility of a myocardium; seldom - development (or aggravation) symptoms of heart failure (puffiness of anklebones, feet, shins), the expressed lowering of arterial pressure, manifestation of a vasomotor spasm (decrease in peripheric circulation, a cold snap of the lower extremities, Reynaud's syndrome), a stethalgia.

From the alimentary system: often - nausea, vomiting, an abdominal pain, a lock or diarrhea; seldom - dryness of a mucous membrane of an oral cavity, an abnormal liver function (dark urine, yellowness of scleras or skin, a cholestasia), taste change.

From respiratory system: seldom - a nose congestion, an asthma at purpose of high doses (selectivity loss) and/or at predisposed patients - laringo-and a bronchospasm.

From an organ of sight: seldom - dryness and morbidity of eyes, reduction of secretion of the lacrimal glands, dryness and morbidity of eyes, conjunctivitis; very seldom - vision disorders.

From integuments: seldom - the increased sweating, a dermahemia, a dieback, psoriazopodobny skin reactions, an aggravation of a course of psoriasis.

Allergic reactions: seldom - skin rash, an itch, a small tortoiseshell.

From endocrine system: very seldom - a hyperglycemia at patients a diabetes mellitus 2 types, a hypoglycemia at the patients receiving insulin, a hypothyroid state.

Influence on a fruit: pre-natal growth inhibition, hypoglycemia, bradycardia.

Others: dorsodynia, arthralgia, weakening of a libido, decrease in a potentiality, syndrome of "cancellation" (strengthening of attacks of stenocardia, increase in arterial pressure).

Laboratory indicators: increase in a caption of antinuclear antibodies which only in exceptional cases is followed by the clinical manifestations like a system lupus erythematosus which are taking place at the treatment termination is in rare instances observed.

If the side effects specified in the instruction are aggravated, or you noticed any other side effects which are not specified in the instruction, report about it to the doctor.

Interaction with other medicines:

Contraindicated combinations. Floktafenin. In case of shock or the arterial hypotension caused floktafeniny β-adrenoblockers cause reduction of compensatory cardiovascular reactions.

Sultoprid. The expressed bradycardia (the additive effect).

Not recommended combinations. Simultaneous use of Reserpinum, α-Methyldopums, a guanfatsin and cardiac glycosides with betaksololy can lead to heavy bradycardia, automatism disturbance therefore they should be applied with extra care.

It is not necessary to apply бетаксолол and sympathomimetics.

Fingolimod. Risk of strengthening of bradycardia, especially at the patients receiving β-adrenoblockers..........

Epinephrinum (adrenaline). Against the background of a betaksolol the effect of Epinephrinum is weakened.

Amiodaronum. Disturbances of contractility, automatism and conductivity (oppression of sympathetic compensatory mechanisms).

Iodinated substances. At administration of iodinated contrast mediums, β-adrenoblockers reduce compensatory cardiovascular reactions. If it is possible, then before carrying out a radiographic research using iodinated contrast means it is necessary to cancel therapy betaksololy.

Antacids. At combined use with antiacid means reduction of β-adrenoblockers of absorption is possible, that leads to decrease in hypotensive action of a betaksolol.

The combinations demanding use with care. At combined use of a betaksolol and verapamil drugs, diltiazem also mibefradit - disturbances of automatism of heart (the expressed bradycardia, a stop of a sinus node), disturbances of atrioventricular conductivity, heart failure are possible. This combination can be applied only at careful clinical and electrocardiographic control, especially at elderly patients.

Inhalation galogensoderzhashchy anesthetics. β-adrenoblockers reduce hypotensive action of a betaksolol (during surgical intervention the effect of β-adrenoceptors can be eliminated with β-adrenostimulyator).

As a rule, therapy by β-adrenoblockers should not be stopped, and sharp drug withdrawal to sleduyetizbegat anyway. The anesthesiologist needs to be informed of the carried-out treatment.

The drugs capable to cause type arrhythmia - "pirouette" (except a sultoprid). Antiarrhytmic medicines: соталол, the class IA (quinidine, hydroquinidine and Disopyramidum) and a class III (дофетилид, ибутилид), some neuroleptics from group of a fenotiazin (Chlorpromazinum, циамемазин, levomepromazinum, thioridazine), benzamides (амисульприд, Sulpiridum, тиаприд), phenyl propyl ketones (Droperidolum, a haloperidol), other neuroleptics (Pimozidum) and other drugs (цизаприд, difemanit, intravenous erythromycin, галофантрин, мизоластин, moxifloxacin, pentamidine, intravenous Spheromycinum and Vincaminum). Increase in risk of ventricular arrhythmia is possible.

Clinical and electrocardiographic control is required.

Propafenon. Disturbance of contractility, automatism and conductivity (suppression of sympathetic compensatory mechanisms).

Clinical and electrocardiographic control is required.

Baclofenum. Strengthening of hypotensive action. Control of arterial pressure and dose adjustment of an antihypertensive in case of need is necessary.

Insulin and hypoglycemic means for intake (sulphonylurea derivatives)

All β-adrenoblockers can disguise certain symptoms of a hypoglycemia: heartbeat and tachycardia.

The patient has to be warned about need of strengthening of self-checking behind concentration of glucose in blood, especially in an initiation of treatment.

Cholinesterase inhibitors (амбеномиум, donepezil, Galantaminum, неостигмин, pyridostigmine, ривастигмин, такрин)

Risk of strengthening of bradycardia (additive action).

Regular clinical control is required.

Hypotensive medicines of the central action (апраклонидин, clonidine, моксонидин, рилменидин)

Substantial increase of arterial pressure at sharp cancellation of hypotensive medicine of the central action.

It is necessary to avoid sharp cancellation of an antihypertensive and to carry out clinical control.

Lidocaine intravenously (as antiarrhytmic means). Increase in concentration of lidocaine in a blood plasma with possible increase in undesirable neurologic symptoms and effects from cardiovascular system (decrease in metabolism of lidocaine in a liver). Clinical and electrocardiographic observation and, perhaps, control of concentration of lidocaine in a blood plasma is recommended during treatment by β-adrenoblockers and after its termination. If necessary - lidocaine dose adjustment.

Combinations which should be taken into account. Non-steroidal anti-inflammatory drugs (systemically), including the selection inhibitors of cyclooxygenase (TsOG-2). Decrease in hypotensive effect (oppression of synthesis of prostaglandins non-steroidal anti-inflammatory drugs and delay of water and sodium pyrazolon derivatives).

Tricyclic antidepressants (like Imipraminum), neuroleptics. Strengthening of hypotensive effect and risk of orthostatic hypotension (additive action).

Meflokhin. Risk of bradycardia (additive action).

Dipiridamolum (intravenously). Strengthening of hypotensive effect.

α-adrenoblockers ((((((((((альфузозин, доксазозин, Prazozinum, тамсулозин, теразозин). Strengthening of hypotensive effect. The increased risk of orthostatic hypotension.

Amifostin. Strengthening of hypotensive effect. The allergens used for an immunotherapy or extracts of allergens for skin tests increase risk of emergence of heavy system allergic reactions or an anaphylaxis at the patients receiving бетаксолол.

Phenytoinum at intravenous administration increases expressiveness of cardiodepressive action and probability of a lowering of arterial pressure. Betaksolol reduces clearance of xanthines (except Diphyllinum) and increases their concentration in a blood plasma, especially at patients with initially increased clearance of theophylline (for example, under the influence of smoking). The hypotensive effect is weakened by estrogen (a sodium delay).

Nifedipine can lead to a considerable lowering of arterial pressure.

Diuretics, sympatholytics, гидралазин and other hypotensive medicines can lead to an excessive lowering of arterial pressure.

Extends action of not depolarizing muscle relaxants and anticoagulating effect of coumarins.

Ethanol, sedative and somnolent medicines strengthen oppression of the central nervous system.

Simultaneous use with monoamine oxidase inhibitors owing to considerable strengthening of hypotensive action is not recommended, having rummaged in treatment between reception of monoamine oxidase inhibitors and a betaksolola has to make not less than 14 days.

Not hydrogenated alkaloids of an ergot increase risk of development of disturbances of peripheric circulation.

Contraindications:

- hypersensitivity to a betaksolol, other β-adrenoblockers and other components of drug;

- the acute heart failure, chronic heart failure in a decompensation stage demanding performing inotropic therapy;

- cardiogenic shock;

- anaphylactic reactions in the anamnesis;

- an atrioventricular block of II and III degrees (without connection of an artificial pacemaker);

- Printsmetal's stenocardia;

- a sick sinus syndrome (including sinuatrial blockade);

- heavy bradycardia (less than 50 beats/min);

- arterial hypotension (systolic arterial pressure is less than 90 mm Hg);

- heavy disturbances of peripheric circulation;

- severe forms of bronchial asthma and chronic obstructive pulmonary disease;

- a pheochromocytoma (without simultaneous use of α-adrenoblockers))))))))));

- a combination therapy with sultopridy and floktafeniny;

- concomitant use of monoamine oxidase inhibitors (MAO);

- simultaneous intravenous administration of blockers of "slow" calcium channels like verapamil and diltiazem and other antiarrhytmic means, for example Amiodaronum, Disopyramidum, etc.);

- metabolic acidosis;

- a cardiomegaly (without symptoms of heart failure);

- age up to 18 years (efficiency and safety are not established).

Due to the lactose presence this drug is contraindicated at an inborn galactosemia; sprue of a glucose/galactose or deficit of lactase.

With care. Allergic reactions in the anamnesis, obliterating diseases of peripheral vessels (the "alternating" lameness, Reynaud's syndrome), a liver failure, a renal failure, a hemodialysis, a myasthenia, a depression (including in the anamnesis), advanced age, an atrioventricular block of the I degree, a chronic obstructive pulmonary disease (bronchial asthma), emphysema of lungs, psoriasis, chronic heart failure, a thyrotoxicosis, a diabetes mellitus.

Performing the desensibilizing therapy.

Overdose:

Symptoms. Heavy bradycardia, dizziness, an atrioventricular block, the expressed lowering of arterial pressure, arrhythmias, ventricular premature ventricular contraction, an unconscious state, heart failure, breath difficulty, a bronchospasm, cyanosis of nails of fingers and palms, spasms.

Treatment. A gastric lavage, use of the adsorbing means.

In case of development of bradycardia it is recommended:

- atropine of 1-2 mg intravenously;

- then (in case of need) slow infusion of 25 mkg of an izoprenalin or infusion of Dobutaminum of 2,5-10 mkg/kg/min.;

At bradycardia temporary statement of an artificial pacemaker can sometimes be required.

At the expressed lowering of arterial pressure it is recommended:

- intravenous administration of plasma substituting solutions and angiotonic drugs.

At a bronchospasm:

- purpose of bronchodilators, including β2-адреномиметиков and/or Aminophyllinum.

In case of heart failure (decompensation) at newborns whose mothers during pregnancy accepted β-adrenoblockers, it is recommended:

- hospitalization in intensive care unit;

- изопреналин and Dobutaminum: observation of the specialist is long and usually in high doses.

Storage conditions:

In the dry, protected from light place, at a temperature not above 25 °C. To store in the places unavailable to children. A period of validity - 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 20 mg. Packaging: on 10 tablets in a blister strip packaging. 1, 2, 3, 5 or 10 blister strip packagings together with the application instruction in a pack from a cardboard.