Betaxolol - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate (sugar milk) 128.1 mg, microcrystalline cellulose 85.8 mg, magnesium stearate 2.5 mg, carboxymethyl starch sodium (primogel) 7.4 mg, aerosil (silicon dioxide colloid) 1.2 mg;

film sheath: Opapray II white 85F18422 [polyvinyl alcohol 2.0 mg, titanium dioxide 1.25 mg, macrogol (polyethylene glycol) 1.01 mg, talc 0.74 mg].

Description:

Tablets are white or almost white, biconvex round, covered with a film membrane, with a risk. On the cut, the core is white or almost white.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

S.01.E.D.02 Betaxolol

Pharmacodynamics:

Betaxolol is characterized by three pharmacological properties:

- cardioselective β-adrenergic blocking action;

- absence of partial agonistic activity (that is, it does not show its own sympathomimetic action);

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

The selective effect of betaxolol on β₁-adrenoceptors is not absolute, so when applied in high doses, it is possible that betaxolol affects β₂-adrenoreceptors, located mainly in the smooth muscles of the bronchi and vessels (however, the effect of betaxolol on β₂-adrenoceptors are much weaker than those of non-selective β-blockers).

When using betaxolol, its blocking β₁-adrenoreceptors activity is manifested following pharmacodynamic effects:

- decrease in the number of cardiac contractions at rest and under physical exertion (due to blockade βadrenoreceptors in the sinus node, which in combination with the absence of internal sympathomimetic activity in betaxolol leads to a slowdown of the automatism of the sinus node);

- decrease in cardiac, ejection at rest and during exercise due to competitive antagonism with catecholamines in peripheral (especially cardiac) adrenergic nerve endings;

- decrease in systolic and diastolic blood pressure at rest and under physical exertion (the mechanism of hypotensive action is described below);

- a decrease in the reflex of orthostatic tachycardia.

As a result of these effects, there is a decrease in the load on the heart at rest and under physical exertion. The mechanism of antihypertensive action of β-adrenoblockers is not fully established.

The following mechanisms of hypotensive action are suggested for β-adrenoblockers:

- decreased cardiac output;

- elimination of spasm of peripheral arteries (due to central action leading to a decrease in sympathetic impulses to the periphery, to vessels, and by inhibiting renin activity).

The hypotensive effect of betaxolol with its long-term intake does not decrease. With a single dose of betaxolol during the day (from 5 to 40 mg), the hypotensive effect is the same after 3-4 hours (time to reach C_mOh betaxolol in the blood) and after 24 hours (before taking the next dose).

When taking 5 mg and 10 mg of betaxolol, its hypotensive effect is, respectively, 50% and 80% of the hypotensive effect with 20 mg of betaxolol. Thus, in the dose range of 5-20 mg, the dose-dependence of the hypotensive effect is observed, and with an increase in the dose from 10 mg to 20 mg, the increase in the hypotensive effect is insignificant. Increasing the dose from 20 mg to 40 mg slightly changes the hypotensive effect of betaxolol. The maximum hypotensive effect of each dose of betaxolol is achieved after 1-2 weeks.

In contrast to the hypotensive effect of betaxolol, the effect of decreasing the number of cardiac contractions with an increase in its dose (from 10 mg to 40 mg) does not increase.

Besides, betaxolol It can slow the conductivity of the atrioventricular node.

Pharmacokinetics:

Suction

Betaxolol is rapidly and completely (100%) absorbed from the gastrointestinal tract after ingestion, bioavailability is about 85%.The maximum concentration in the blood plasma is reached in 2-4 hours. Betaxolol binds to blood plasma proteins by about 50%.

Permeability through the blood-brain and placental barrier is low. Secretion of breast milk is insignificant.

Metabolism

The volume of distribution is about 6 l / kg. Betaxolol metabolized in the liver with the formation of inactive metabolites. The solubility in fats is moderate.

Excretion

It is excreted by the kidneys in the form of metabolites (more than 80%), 10-15% unchanged. Half-life (T_1/2) of betaxolol is 15-20 hours. T_1/2 when the liver function is impaired by 33%, but the clearance does not change; with a violation of kidney function T_1/2 doubles (lower doses are necessary).

It is not removed during hemodialysis.

Indications:

- Arterial hypertension;

- Pthe prevention of angina pectoris attacks.

Contraindications:

- Pincreased sensitivity to betaxolol, other β-blockers and other components of the drug;

- acute heart failure, chronic heart failure in the stage of decompensation, requiring inotropic therapy;

- cardiogenic shock;

- anaphylactic reactions in the anamnesis;

- atrioventricular blockade of II and III degree (without connection of an artificial pacemaker);

- angina of Prinzmetal;

- syndrome of weakness of the sinus node (including sinoatrial blockade);

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

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

- severe violations of peripheral circulation;

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

- pheochromocytoma (without simultaneous application αadrenoblockers);

- combined therapy with sultopride and floktaphenin;

- simultaneous administration of monoamine oxidase inhibitors (MAO);

- simultaneous intravenous administration of blockers of "slow" calcium channels such as verapamil and diltiazem and other antiarrhythmics, for example amiodarone, disopyramide, etc.);

- metabolic acidosis;

- cardiomegaly (no signs of heart failure);

- age to 18 years (efficacy and safety not established).

Due to the presence of lactose, this drug is contraindicated in congenital galactosemia; glucose / galactose malabsorption syndrome or lactase deficiency.

Carefully:

Allergic reactions in history, obliterating peripheral vascular diseases (intermittent claudication, Raynaud's syndrome), liver failure, renal dysfunction, hemodialysis, myasthenia gravis, depression (including history), advanced age, atrioventricular block of degree I, chronic obstructive lung disease (bronchial asthma), pulmonary emphysema, psoriasis, chronic heart failure, thyrotoxicosis, diabetes mellitus.

Carrying out desensitizing therapy.

Pregnancy and lactation:

Teratogenicity

There was no teratogenic effect of the drug in animal experiments. To date, no teratogenic effects have been observed in humans, and controlled prospective studies have not shown congenital malformations.

Application in pregnancy is possible only if the benefit to the mother exceeds the potential risk to the fetus and / or the child.

Breast-feeding

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

The risk of hypoglycemia or bradycardia has not been investigated, so breastfeeding during treatment should be discontinued.

Dosing and Administration:

A drug Betaxolol take in, do not chew, drink with a sufficient amount of liquid.

The initial dose of Betaxolol preparation for both indications is 10 mg / day (1/2 tablet 20 mg), maintaining a dose of 20 mg / day.

Dosage in patients with renal and / or liver failure

Patients with mild to moderate renal failure and / or liver failure are not required to correct the initial dose, however, regular medical supervision is necessary at the beginning of treatment.

Patients with severe renal insufficiency (creatinine clearance less than 20 ml / min) the recommended initial dose should not exceed 10 mg. The maximum daily dose of the drug is 20 mg.

Side effects:

WHO classification of unwanted adverse reactions according to the frequency of development

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 / 10,000 assignments	(< 0,01%)

From the central nervous system:

often - increased fatigue, weakness, dizziness, headache, drowsiness or insomnia, nightmares; rarely - depression;

very rarely - anxiety, confusion or short-term memory loss, hallucinations, asthenic syndrome, muscle weakness, paresthesia in the extremities (in patients with "intermittent" lameness, Raynaud's syndrome), tremor.

From the cardiovascular system:

often - sinus bradycardia, palpitations, orthostatic hypotension, disturbance of myocardial conductivity, atrioventricular blockade (up to cardiac arrest), arrhythmias, weakening of myocardial contractility;

rarely - the development (or worsening) of symptoms of heart failure (swelling of the ankles, feet, legs), a marked decrease in arterial pressure, the manifestation of angiospasm (decreased peripheral circulation, lower extremities cooling, Raynaud's syndrome), chest pain.

From the digestive system:

often - nausea, vomiting, abdominal pain, constipation or diarrhea;

rarely - dryness of the oral mucosa, impaired liver function (dark urine, icteric sclera or skin, cholestasis), taste change.

From the respiratory system:

rarely - nasal congestion, shortness of breath in the appointment of large doses (loss of selectivity) and / or in predisposed patients - laryngo- and bronchospasm.

From the side of the organ of vision:

rarely - dryness and soreness of the eyes, a decrease in the secretion of the lacrimal glands, dryness and soreness of the eyes, conjunctivitis; very rarely - visual impairment.

From the skin:

rarely - increased sweating, skin hyperemia, exanthema, psoriasis-like skin reactions, exacerbation of psoriasis.

Allergic reactions:

rarely - skin rash, itching, hives.

From the endocrine system:

very rarely - hyperglycemia in patients with type 2 diabetes, hypoglycemia in patients receiving insulin, hypothyroid status.

Influence on the fetus: intrauterine growth retardation, hypoglycemia, bradycardia.

Other: pain in the back, arthralgia, weakening of libido, decreased potency, withdrawal syndrome (increased angina attacks, increased blood pressure).

Laboratory indicators:

In rare cases, an increase in the titer of antinuclear antibodies is observed, which only in exceptional cases is accompanied by clinical manifestations of the type of systemic lupus erythematosus that occur when treatment is discontinued.

If the side effects indicated in the manual are aggravated, or if you notice any other side effects not listed in the instructions, inform the doctor about it.

Overdose:

Symptoms

Severe bradycardia, dizziness, atrioventricular blockade, marked decrease in arterial pressure, arrhythmias, ventricular extrasystole, syncope, heart failure, difficulty breathing, bronchospasm, cyanosis of the fingernails and palms, convulsions.

Treatment

Gastric lavage, the use of absorbents.

In case of development of a bradycardia it is recommended:

- atropine 1-2 mg intravenously;

- then (if necessary) a slow infusion of 25 μg of isoprenaline or a dobutamine infusion of 2.5-10 μg / kg / min;

With bradycardia, it may sometimes be necessary to temporarily set up an artificial pacemaker.

At the expressed depression of arterial pressure it is recommended:

- intravenous injection of plasma-substituting solutions and vasopressor preparations.

When bronhospazme:

- the appointment of bronchodilators, including β₂adrenomimetics and / or aminophylline.

In the case of heart failure (decompensation) in newborns whose mothers took beta-blockers during pregnancy, it is recommended:

- hospitalization in the intensive care unit;

- isoprenaline and dobutamine: prolonged and usually in high doses, supervision by a specialist.

Interaction:

Contraindicated combinations

Floktaphenin

In the case of shock or arterial hypotension caused by floktaphenin, β-adrenoblockers cause a decrease in compensatory cardiovascular reactions.

Sulphoprid

Pronounced bradycardia (additive effect).

Unrecommended combinations

The simultaneous use of reserpine, α-methyldopa, guanfacin and cardiac glycosides with betaxolol can lead to severe bradycardia, a violation of automatism, so they should be used with extreme caution.

Do not use betaxolol and sympathomimetics.

Fingolimod

The risk of increased bradycardia, especially in patients receiving β-blockers.

Epinephrine (adrenaline)

Against the background of betaxolol, the effect of epinephrine is weakened.

Amiodarone

Violations of contractility, automatism and conduction (suppression of sympathetic compensatory mechanisms).

Iodine-containing substances

With the introduction of iodine-containing contrast agents, β-adrenoblockers reduce compensatory cardiovascular reactions. If possible, before the X-ray examination using iodine-containing contrast agents, therapy with betaxolol should be discontinued.

Antacids

When combined with antacids, it is possible to reduce the absorption of β-adrenoblockers, which leads to a decrease in the hypotensive effect of betaxolol.

Combinations requiring use with caution

With the combined use of betaxolol and preparations of the type verapamil, diltiazem and mibefradil - possible violations of the automatism of the heart (pronounced bradycardia, stopping the sinus node), violations of atrioventricular conduction, heart failure. This combination can be used only with careful clinical and electrocardiographic monitoring, especially in elderly patients.

Inhaled halogenated anesthetics

β-adrenoblockers reduce the hypotensive effect of betaxolol (during the surgical intervention, the effect of β-adrenergic receptors can be eliminated by β-adrenostimulators).

As a rule, therapy with β-blockers should not be discontinued, and abrupt withdrawal of the drug should be avoided in any case. An anesthesiologist should be informed of the treatment.

Preparations that can cause arrhythmia of the type - "pirouette" (except sultopride)

Antiarrhythmic drugs: sotalol, class IA (quinidine, hydroquinidine and disopyramide) and class III (dofetilide, ibutilide), some neuroleptics from the phenothiazine group (chlorpromazine, cyamemazine, levomepromazine, thioridazine), benzamides (amisulpride, sulpiride, tiapride), butyrophenones (droperidol, haloperidol), other neuroleptics (pimozide) and other drugs (cisapride, difemanyl, intravenous erythromycin, halofantrine, misolastine, moxifloxacin, pentamidine, intravenous spiramycin and wincamine). An increased risk of ventricular arrhythmia is possible.

Clinical and electrocardiographic monitoring is required.

Propafenone

Violation of contractility, automatism and conduction (suppression of sympathetic compensatory mechanisms).

Clinical and electrocardiographic monitoring is required.

Baclofen

Strengthening of hypotensive action. It is necessary to monitor blood pressure and correct the dose of an antihypertensive agent if necessary.

Insulin and hypoglycemic agents for oral administration (sulfonylureas derivatives)

All β-adrenoblockers can mask certain symptoms of hypoglycemia: palpitation and tachycardia.

The patient should be warned about the need to strengthen self-monitoring for the concentration of glucose in the blood, especially at the beginning of treatment.

Cholinesterase inhibitors (ambenomium, donepezil, galantamine, neostigmine, pyridostigmine, rivastigmine, Tacrine)

Risk of increased bradycardia (additive effect).

Regular clinical control is required.

Hypotensive drugs of central action (apraklonidine, clonidine, moxonidine, rilmenidine)

Significant increase in blood pressure with a sharp reversal of the antihypertensive drug of central action.

It is necessary to avoid a sharp abolition of the antihypertensive agent and to carry out clinical control.

Lidocaine intravenously (as an antiarrhythmic drug)

An increase in the concentration of lidocaine in the blood plasma with a possible increase in unwanted neurological symptoms and effects on the part of the cardiovascular system (a decrease in the metabolism of lidocaine in the liver). Clinical and electrocardiographic observation is recommended and, probably, control of lidocaine concentration in blood plasma during treatment with β-blockers and after its termination.If necessary, adjust the dose of lidocaine.

Combinations that should be taken into account

Non-steroidal anti-inflammatory drugs (systemically), including selective inhibitors of cyclooxygenase (COX-2)

Reduction of hypotensive effect (oppression of prostaglandin synthesis by non-steroidal anti-inflammatory drugs and water retention and sodium pyrazolone derivatives).

Tricyclic antidepressants (such as imipramine), antipsychotics

Strengthening the hypotensive effect and the risk of orthostatic hypotension (additive effect).

Meflokhin

Risk of bradycardia (additive effect).

Dipyridamole (intravenously)

Strengthening of the hypotensive effect.

α-adrenoblockers (alfuzosin, doxazosin, prazozin, tamsulosin, terazosin)

Strengthening of the hypotensive effect. Increased risk of orthostatic hypotension.

Amifostine

Strengthening of the hypotensive effect. Allergens used for immunotherapy or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving betaxolol.

Phenytoin with intravenous administration increases the severity of cardiodepressive action and the likelihood of lowering blood pressure. Betaxolol reduces the clearance of xanthines (except diphylline) and increases their concentration in blood plasma, especially in patients with initially elevated clearance of theophylline (for example, under the influence of smoking). The hypotensive effect is weakened by estrogens (sodium retention).

Nifedipine can lead to a significant reduction in blood pressure.

Diuretics, sympatholytics, hydralazine and other antihypertensive drugs can lead to excessive lowering of blood pressure.

Lengthens the effect of nondepolarizing muscle relaxants and anticoagulant effect of coumarins.

Ethanol, sedative and hypnotic drugs increase the inhibition of the central nervous system.

It is not recommended simultaneous use with monoamine oxidase inhibitors due to a significant increase in antihypertensive effect, a break in treatment between taking monoamine oxidase inhibitors and betaxolol should be at least 14 days.

Unhydrated ergot alkaloids increase the risk of peripheral circulatory disorders.

Special instructions:

Treatment of patients with angina should never be interrupted abruptly: sudden withdrawal can lead to severe heart rhythm disturbances, myocardial infarction or sudden death.The dose should be reduced gradually, that is, within 1-2 weeks, and if necessary, it is possible to start substitution treatment simultaneously, in order to avoid the progression of the disease.

It is necessary to monitor patients receiving Betaxolol, it should include monitoring the number of heartbeats and blood pressure (at the beginning of treatment daily, then once in 3-4 months), the concentration of glucose in the blood in patients with diabetes mellitus (1 every 4-5 months), control function kidneys in elderly patients (1 time in 4-5 months).

You should teach the patient how to count the number of heartbeats and instruct you about the need for medical advice when the number of heartbeats is less than 50 beats / minute.

Approximately in 20% of patients with angina, β-adrenoblockers are ineffective. The main causes are severe coronary atherosclerosis with a low threshold of ischemia (the number of heartbeats at the time of development of an anginal attack is less than 100 beats / min) and increased end-diastolic pressure of the left ventricle, which breaks the subendocardial blood flow.

With the simultaneous administration of clonidine, its administration can be stopped only a few days after Betaxolol has been withdrawn.

Betaxolol should be discontinued before testing the blood and urine levels of catecholamines, normetanephrine and vanillin-mandelic acid; titers of antinuclear antibodies.

Bronchial asthma and chronic obstructive pulmonary disease

β-blockers can be administered only to patients with moderate disease severity, with a selective β-adrenoblocker in a low initial dose. Before the start of treatment it is recommended to perform an evaluation of the function of breathing. When developing seizures during treatment, bronchodilators - β₂-adrenomimetics.

Heart failure

In patients with controlled heart failure, if necessary Betaxolol can be used in very low, gradually increasing doses, under strict medical supervision.

Bradycardia

The dose should be reduced if the number of heartbeats at rest is below 50-55 beats / min and the patient has clinical manifestations of bradycardia. Atrioventricular block of degree I

Given the negative dromotropic effect of β-blockers, with blockade of the I degree the drug should be used with caution.

Angina pectoris

β-adrenoblockers can increase the number and duration of seizures in patients suffering from Prinzmetal angina pectoris. The use of cardioselective β₁-adrenoconcretors is possible in less severe and mixed forms, provided that the treatment is performed in combination with vasodilators.

Violations of peripheral circulation

β-adrenoblockers can lead to worsening of patients with impaired peripheral circulation (Raynaud's disease or Raynaud's syndrome, arteritis or chronic obliterating diseases of lower limb arteries).

Pheochromocytoma

In the case of the use of β-adrenoblockers in the treatment of arterial hypertension caused by pheochromocytoma, careful monitoring of blood pressure is required.

Elderly patients

Treatment of elderly patients should start with the lowest possible and well tolerated dose and under strict supervision.

Patients with renal insufficiency

The dose should be adjusted depending on the concentration of creatinine in the blood or the clearance of creatinine (see "Method of administration and dose").

Patients with diabetes mellitus

It is necessary to warn the patient about the need to strengthen self-monitoring of glucose concentration in the blood at the beginning of treatment. The initial symptoms of hypoglycemia can be masked, especially tachycardia, palpitations and sweating.

Psoriasis

A thorough evaluation of the need for prescribing is required, as there are reports of worsening of the condition during treatment with β-blockers.

Allergic reactions

In patients prone to severe anaphylactic reactions, especially those associated with the use of floktaphenin or during desensitization, therapy with β-blockers can lead to further intensification of reactions and a decrease in the effectiveness of therapy.

General anesthesia

β-adrenoblockers disguise reflex tachycardia and increase the risk of developing arterial hypotension. Continuation of therapy with β-blockers reduces the risk of arrhythmia, myocardial ischemia and hypertensive crises. An anesthesiologist should be informed that the patient was receiving treatment with β-adrenoblockers.

- If cessation of treatment is deemed necessary, then it is considered that cessation of therapy for 48 hours allows to restore sensitivity to catecholamines.

- Therapy with β-blockers should not be interrupted in the following cases:

in patients with coronary insufficiency it is desirable to continue therapy up to surgical intervention, taking into account the risk associated with the sudden abolition of β-blockers;
in case of emergency surgical interventions or in cases where discontinuation of therapy is not possible, the patient should be protected from the effects of excitation of the vagus nerve by appropriate premedication with atropine, with repetition if necessary. For general anesthesia, it is necessary to use medications, the least depressing myocardium.

- The risk of developing anaphylactic reactions should be considered.

Thyrotoxicosis

Symptoms of thyrotoxicosis can be masked by therapy with β-blockers.

Athletes

Athletes should consider that the drug contains an active substance, which can give a positive reaction when performing doping tests.

For the duration of treatment, exclude the use of ethanol.

Patients using contact lenses should take into account that the tear fluid can be reduced against the background of treatment.

In tobacco smoking, the effectiveness of β-blockers is lower.

In newborns, whose mothers were treated with β-blockers, the effect of the latter persists for several days after birth. Although this residual effect may not have clinical consequences, nevertheless it is possible to develop a heart defect requiring intensive care for a newborn (see "Overdose"). In such a situation, the introduction of blood volume-increasing solutions (the risk of developing acute pulmonary edema) should be avoided. There are also reports of bradycardia, respiratory distress syndrome and hypoglycemia. Therefore, careful monitoring of newborns in specialized conditions is recommended (monitoring the number of heartbeats and the concentration of glucose in the blood during the first 3-5 days of life).

Effect on the ability to drive transp. cf. and fur:

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 20 mg.

Packaging:

10 tablets per contour cell pack.

1, 2, 3, 5 or 10 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after expiration date, indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002502

Date of registration:16.06.2014

Expiration Date:16.06.2019

The owner of the registration certificate:MOSCOW ENDOCRINE FACTORY, FSUE MOSCOW ENDOCRINE FACTORY, FSUE Russia

Manufacturer: & nbsp

MOSCOW ENDOCRINE FACTORY, FSUE Russia

Representation: & nbspMOSCOW ENDOCRINE FACTORY FGUP MOSCOW ENDOCRINE FACTORY FGUP Russia

Information update date: & nbsp24.01.2017

Illustrated instructions

Instructions

Betaxolol (Betaxolol)