Betaxolol (Tablets, Drops) Instructions for Use

ATC Code

C07AB05 (Betaxolol)

Active Substance

Betaxolol (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Beta₁-adrenergic blocker

Pharmacotherapeutic Group

Beta-adrenergic blocking agents; selective beta-adrenergic blocking agents

Pharmacological Action

Cardioselective beta₁-adrenergic blocker without intrinsic sympathomimetic activity. Betaxolol is characterized by three pharmacological properties: cardioselective beta₁-adrenergic blocking action; absence of partial agonistic activity (lack of intrinsic sympathomimetic activity); weak membrane-stabilizing action (similar to the action of quinidine or local anesthetics) at concentrations exceeding therapeutic levels.

It should be noted that the selective effect of betaxolol on β₁-adrenergic receptors is not absolute, as when used in high doses, an effect on β₂-adrenergic receptors, located mainly in the smooth muscles of the bronchi and blood vessels, is possible (however, the effect of betaxolol on β₂-adrenergic receptors is significantly weaker than that of non-selective beta-blockers).

When betaxolol is used, its β₁-adrenergic receptor blocking activity is manifested by the following pharmacodynamic effects: decrease in heart rate at rest and during physical exertion (due to blockade of beta-adrenergic receptors in the sinus node, which, combined with the absence of intrinsic sympathomimetic activity in betaxolol, leads to slowing of sinus node automaticity); reduction of cardiac output at rest and during exercise due to competitive antagonism with catecholamines in peripheral (especially cardiac) adrenergic nerve endings; reduction of systolic and diastolic blood pressure at rest and during physical exertion (the mechanism of antihypertensive action is described below); reduction of orthostatic tachycardia reflex.

As a result of these effects, the load on the heart at rest and during physical exertion is reduced.

The mechanism of the antihypertensive action of beta-blockers has not been fully established.

The following mechanisms of antihypertensive action are assumed for beta-blockers: reduction of cardiac output; elimination of peripheral arterial spasm (due to central action leading to a reduction in sympathetic impulse transmission to the periphery, to the vessels, and due to inhibition of renin activity).

The antihypertensive effect of betaxolol does not decrease with its long-term use. With a single daily dose of betaxolol (from 5 to 40 mg), the antihypertensive effect is the same after 3-4 hours (the time to reach C_max of betaxolol in the blood) and after 24 hours (before taking the next dose). When taking 5 mg and 10 mg of betaxolol, its antihypertensive effect is 50% and 80%, respectively, of the antihypertensive effect when taking 20 mg of betaxolol.

Thus, in the dose range of 5-20 mg, a dose-dependence of the antihypertensive effect is observed, and when the dose is increased from 10 mg to 20 mg, the increase in the antihypertensive effect is insignificant. Increasing the dose from 20 mg to 40 mg slightly changes the antihypertensive effect of betaxolol. The maximum antihypertensive effect of each dose of betaxolol is achieved after 1-2 weeks.

In contrast to the antihypertensive effect of betaxolol, the effect of reducing heart rate does not increase with increasing its dose (from 10 mg to 40 mg).

In addition, Betaxolol is able to slow AV node conduction.

Pharmacokinetics

After oral administration, Betaxolol is rapidly and completely (100%) absorbed from the gastrointestinal tract. C_max of betaxolol in blood plasma is reached in 2-4 hours. Betaxolol has a slight first-pass effect through the liver and high bioavailability – about 85%. Differences in its plasma concentrations in different patients or in one patient during long-term use have minor variations, which is associated with the high bioavailability of betaxolol. Betaxolol binds to plasma proteins by approximately 50%. It poorly penetrates the blood-brain barrier and placental barrier, and is excreted in breast milk to a small extent. V_d is about 6 L/kg. Fat solubility is moderate. Betaxolol is metabolized in the liver to form inactive metabolites. It is excreted by the kidneys as metabolites (more than 80%), 10-15% unchanged. T_1/2 of betaxolol is 15-20 hours. It is not removed by hemodialysis.

Indications

Arterial hypertension (in monotherapy and as part of combination therapy); prevention of exertional angina attacks (in monotherapy and as part of combination therapy).

ICD codes

Dosage Regimen

Drops

Apply topically, instill into the conjunctival sac 2 times/day. In some patients, stabilization of intraocular pressure occurs over several weeks, so it is recommended to monitor intraocular pressure during the first month of treatment.

Tablets

Take orally.

Initial dose – 10 mg/day. If necessary, after 7-14 days of treatment, the dose is doubled to 20 mg/day.

Maximum daily dose – 40 mg.

Adverse Reactions

Allergic reactions skin rash, itching, urticaria.

Skin and subcutaneous tissue disorders: rarely – various skin reactions, including skin rash, itching, urticaria, psoriasis-like eruptions or exacerbation of psoriasis.

Nervous system disorders: frequently – dizziness, headache, asthenia, insomnia; rarely – depression; very rarely – hallucinations, confusion, nightmares, paresthesia.

Eye disorders: rarely – dry eyes, decreased intraocular pressure (due to the possibility of its reduction under the influence of beta-blockers); very rarely – visual disturbances.

Gastrointestinal disorders frequently – gastralgia, diarrhea, nausea, vomiting.

Metabolism and nutrition disorders very rarely – hypoglycemia, hyperglycemia.

Cardiac and vascular disorders frequently – bradycardia, possibly severe, decrease in skin temperature of the upper and lower extremities; rarely – development (or worsening) of symptoms of heart failure (swelling of the ankles, feet, legs), pronounced decrease in blood pressure, slowing of AV conduction, manifestations of angiospasm: Raynaud’s syndrome, increased peripheral circulatory disorders, including intermittent claudication, increased frequency of angina attacks.

Respiratory, thoracic and mediastinal disorders rarely – bronchospasm.

Reproductive system and breast disorders: frequently – impotence.

Investigations rarely – appearance of antinuclear antibodies, only in exceptional cases combined with clinical manifestations of a lupus-like syndrome, which resolves after discontinuation of treatment.

Other withdrawal syndrome (intensification or increased frequency of angina attacks, increased blood pressure).

Contraindications

Hypersensitivity to betaxolol; severe forms of bronchial asthma and COPD; acute heart failure, chronic heart failure in the stage of decompensation, not compensated by treatment with diuretics, inotropic agents, ACE inhibitors, other vasodilators; cardiogenic shock; AV block II and III degree (without an established artificial pacemaker); Prinzmetal’s angina (monotherapy is contraindicated); sick sinus syndrome (including sinoatrial block); severe bradycardia (heart rate less than 45-50 beats/min); severe forms of Raynaud’s disease and obliterative peripheral arterial diseases; pheochromocytoma without simultaneous use of alpha-blockers; arterial hypotension (systolic BP <100 mm Hg); anaphylactic reactions in history; metabolic acidosis; cardiomegaly (without signs of heart failure); simultaneous use with sultopride and floctafenine; simultaneous use with MAO inhibitors; children and adolescents under 18 years of age.

With caution

In bronchial asthma and chronic obstructive pulmonary disease of moderate severity; chronic heart failure in the compensation stage; with AV block I degree; with obliterative peripheral arterial diseases, Raynaud’s syndrome (except for severe form); with Prinzmetal’s angina; with treated pheochromocytoma; in elderly patients; in renal failure; in hepatic failure; in patients with diabetes mellitus; in psoriasis; when conducting desensitizing therapy.

Use in Pregnancy and Lactation

Use during pregnancy is not recommended and is possible only if the benefit to the mother outweighs the potential risk to the fetus or child.

Beta-blockers, including Betaxolol, are excreted in breast milk. The risk of hypoglycemia or bradycardia in breastfed infants has not been studied, so as a precaution, breastfeeding should be discontinued during treatment.

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Use in Renal Impairment

Use with caution in renal insufficiency.

Pediatric Use

Contraindication: children and adolescents under 18 years of age (efficacy and safety have not been established).

Geriatric Use

Use the drug with caution in elderly patients (treatment should be started with low doses and under careful medical supervision).

Special Precautions

Treatment with betaxolol should not be interrupted abruptly and the recommended dose should not be changed without prior consultation with a doctor, as this may lead to temporary deterioration of cardiac activity. Treatment should not be interrupted suddenly, especially in patients with coronary artery disease, as sudden withdrawal can lead to severe cardiac arrhythmias, myocardial infarction, or cardiac arrest. The dose should be reduced gradually, i.e., over 2 weeks, and if necessary, replacement therapy with another antianginal agent can be started simultaneously to avoid an increase in the frequency of angina attacks.

In patients taking Betaxolol, heart rate and blood pressure should be monitored (daily at the beginning of treatment, then once every 3-4 months), blood glucose concentration in patients with diabetes mellitus (once every 4-5 months), renal function in elderly patients (once every 4-5 months).

When clonidine is used concomitantly, its administration can be discontinued only several days after discontinuation of betaxolol.

Betaxolol should be discontinued before testing the concentration of catecholamines, normetanephrine and vanillylmandelic acid in blood and urine; as well as titers of antinuclear antibodies in the blood.

Beta-blockers can be prescribed only to patients with a moderate degree of severity of the disease, with the choice of a selective beta-blocker in a low initial dose. It is recommended to assess respiratory function before starting treatment.

If the resting heart rate becomes less than 50-55 beats/min, the dose of betaxolol must be reduced.

Beta-blockers may increase the frequency and duration of attacks in patients with Prinzmetal’s angina. The use of cardioselective beta₁-blockers is possible in mild Prinzmetal’s angina or mixed-type angina, provided that treatment is carried out in combination with vasodilators.

Beta-blockers may lead to worsening of the condition in patients with peripheral circulatory disorders (Raynaud’s disease or Raynaud’s syndrome, arteritis or chronic obliterative diseases of the arteries of the lower extremities).

In the case of using beta-blockers for the treatment of arterial hypertension caused by pheochromocytoma, careful blood pressure monitoring is required. The use of betaxolol is possible only against the background of the use of alpha-blockers.

Treatment of elderly patients should be started with a low dose and under strict supervision.

The dose must be adjusted depending on the blood creatinine concentration or creatinine clearance.

The patient should be warned about the need to enhance blood glucose concentration monitoring, including active self-monitoring by the patient, at the beginning of treatment. The patient should be aware that the initial symptoms of hypoglycemia (especially tachycardia, palpitations, and sweating) may be masked by betaxolol.

A thorough assessment of the need to use betaxolol is required, as there are reports of worsening of psoriasis during treatment with beta-blockers.

Beta-blockers, including Betaxolol, may increase sensitivity to allergens and the severity of anaphylactic reactions due to the weakening of adrenergic compensatory regulation under the influence of beta-blockers. Therapy of anaphylactic reactions with epinephrine (adrenaline) does not always give the expected therapeutic effect.

In patients prone to severe anaphylactic reactions, especially those associated with the use of floctafenine or during desensitization, therapy with beta-blockers may lead to further intensification of reactions and reduced treatment effectiveness.

During general anesthesia, the risk of beta-adrenergic receptor blockade (decreased heart rate, decreased cardiac output, decreased systolic and diastolic blood pressure) should be taken into account.

Beta-blockers mask reflex tachycardia and increase the risk of arterial hypotension. Continuation of beta-blocker therapy reduces the risk of arrhythmia, myocardial ischemia, and hypertensive crises. The anesthesiologist should be informed that the patient is receiving treatment with beta-blockers.

If it is necessary to discontinue betaxolol therapy before surgery, this should be done gradually and completed 48 hours before general anesthesia, as it is believed that discontinuation of therapy for 48 hours allows receptor sensitivity to catecholamines to be restored.

Symptoms of thyrotoxicosis may be masked during therapy with beta-blockers.

Athletes should be aware that the drug contains an active substance that may give a positive reaction during doping control tests.

Alcohol consumption should be avoided during treatment.

Patients using contact lenses should take into account that during treatment with beta-blockers, a decrease in tear fluid production is possible.

In smoking patients, the effectiveness of beta-blockers is lower.

Effect on ability to drive vehicles and operate machinery

Caution is required when driving vehicles or engaging in other potentially hazardous activities while taking betaxolol (due to the risk of developing dizziness, weakness, which may reduce attention and speed of psychomotor reactions necessary for these activities).

Drug Interactions

In case of shock or arterial hypotension caused by floctafenine, beta-blockers cause a decrease in compensatory cardiovascular reactions.

With simultaneous use with sultopride, disturbances of cardiac automaticity (severe bradycardia) are possible due to an additional decrease in heart rate.

With simultaneous use with amiodarone – disturbances of contractility, automaticity and conduction (suppression of sympathetic compensatory mechanisms).

With simultaneous use with slow calcium channel blockers (bepridil, diltiazem and verapamil) – disturbances of automaticity (severe bradycardia, sinus arrest), disturbances of AV conduction, heart failure (synergistic effects). Such a combination can be used only under careful clinical and ECG monitoring, especially in elderly patients or at the beginning of treatment.

With simultaneous use with cardiac glycosides – risk of development or worsening of bradycardia, AV block, cardiac arrest.

Simultaneous use with MAO inhibitors is not recommended due to a significant enhancement of the antihypertensive effect of betaxolol; the break in treatment between taking MAO inhibitors and betaxolol should be at least 14 days.

In case of shock or a sharp decrease in blood pressure during the administration of iodine-containing contrast agents, beta-blockers reduce compensatory cardiovascular reactions. If possible, treatment with a beta-blocker should be discontinued before an X-ray examination using iodine-containing contrast agents.

Beta-blockers have a cardiodepressant effect (inhibition of β-adrenergic receptors may be reduced by the administration of beta-adrenergic stimulants). As a rule, treatment with beta-blockers is not discontinued, and in any case, abrupt withdrawal of beta-blockers should be avoided. The anesthesiologist must be informed about the intake of the beta-blocker.

With drugs capable of causing ventricular cardiac arrhythmias, including torsades de pointes ventricular tachycardia: class IA antiarrhythmic agents (quinidine, hydroquinidine and disopyramide) and class III (amiodarone, dofetilide, ibutilide), sotalol, some antipsychotics from the phenothiazine group (chlorpromazine, cyamemazine, levomepromazine, thioridazine), benzamides (amisulpride, sulpiride, tiapride), butyrophenones (droperidol, haloperidol), other antipsychotics (pimozide) and other drugs (cisapride, difemanil, intravenous erythromycin, halofantrine, mizolastine, moxifloxacin, pentamidine, intravenous spiramycin and intravenous vincamine – increased risk of ventricular arrhythmias, in particular torsades de pointes ventricular tachycardia. Clinical and ECG monitoring is required.

With propafenone – disturbances of contractility, automaticity and conduction (suppression of sympathetic compensatory mechanisms). Clinical and ECG monitoring is required.

With baclofen – Enhancement of the antihypertensive effect of betaxolol. Blood pressure monitoring and dose adjustment of betaxolol is necessary if required.

With insulin and oral hypoglycemic agents, sulfonylurea derivatives – all beta-blockers may mask certain symptoms of hypoglycemia, such as palpitations and tachycardia. The patient should be warned about the need to enhance regular blood glucose concentration monitoring, including active self-monitoring by the patient, especially at the beginning of treatment.

With cholinesterase inhibitors (ambenonium, donepezil, galantamine, neostigmine, pyridostigmine, rivastigmine, tacrine) – risk of increased bradycardia (additive effect). Regular clinical monitoring is required.

With centrally acting antihypertensive agents (clonidine, apraclonidine, alpha-methyldopa, guanfacine, moxonidine, rilmenidine) – increased risk of bradycardia, AV conduction disturbances. Significant increase in blood pressure upon abrupt withdrawal of the centrally acting antihypertensive agent. Abrupt withdrawal of the antihypertensive agent should be avoided and clinical monitoring should be carried out.

With lidocaine 10% solution (IV as an antiarrhythmic agent) – an increase in the plasma concentration of lidocaine with a possible increase in undesirable neurological symptoms and cardiovascular system effects (due to reduced metabolism of lidocaine in the liver). Clinical and ECG monitoring and, possibly, monitoring of plasma lidocaine concentration is recommended during treatment with beta-blockers and after its discontinuation. If necessary, adjust the lidocaine dose.

With NSAIDs (systemically acting drugs), including selective COX-2 inhibitors – a reduction in the antihypertensive effect of betaxolol (due to inhibition of prostaglandin synthesis by NSAIDs and sodium and water retention by pyrazolone derivatives).

With slow calcium channel blockers from the dihydropyridine group – mutual enhancement of the antihypertensive action of slow calcium channel blockers and betaxolol, development of heart failure in patients with latent or uncontrolled heart failure. Treatment with beta-blockers may minimize the reflex activation of the sympathetic nervous system in response to vasodilation induced by slow calcium channel blockers from the dihydropyridine group.

With tricyclic antidepressants (such as imipramine), antipsychotics – enhancement of the antihypertensive effect of betaxolol and risk of orthostatic hypotension (additive effect).

With mefloquine – risk of bradycardia (additive effect).

With dipyridamole (IV administration) – enhancement of the antihypertensive effect of betaxolol.

With alpha-blockers, including those used in urology (alfuzosin, doxazosin, prazosin, tamsulosin, terazosin) – enhancement of the antihypertensive effect of betaxolol. Increased risk of orthostatic hypotension.

With amifostine – enhancement of the antihypertensive effect of betaxolol.

With allergens used for immunotherapy or allergen extracts for skin tests – increased risk of severe systemic allergic reactions or anaphylaxis in patients receiving Betaxolol.

With phenytoin (IV administration) – increased severity of the cardiodepressive effect and likelihood of decreased blood pressure.

With xanthines – Betaxolol reduces the clearance of xanthines (except diphylline) and increases their plasma concentration, especially in patients with initially increased theophylline clearance (e.g., due to smoking).

With estrogens – weakening of the antihypertensive effect of betaxolol (sodium and water retention).

With corticosteroids and tetracosactide – weakening of the antihypertensive effect of betaxolol (sodium and water retention).

With diuretics – possible excessive reduction in blood pressure.

With non-depolarizing muscle relaxants – Betaxolol prolongs the action of non-depolarizing muscle relaxants.

With coumarins – enhancement of the anticoagulant effect of coumarins.

With alcohol (ethanol), sedative and hypnotic drugs – enhancement of CNS depression.

With non-hydrogenated ergot alkaloids – non-hydrogenated ergot alkaloids increase the risk of peripheral circulation disorders when taking betaxolol.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.