Lokren^® (Tablets) Instructions for Use

Marketing Authorization Holder

Cheplapharm Arzneimittel, GmbH (Germany)

Manufactured By

Sanofi Winthrop Industrie (France)

ATC Code

C07AB05 (Betaxolol)

Active Substance

Betaxolol (Rec.INN registered by WHO)

Dosage Form

Lokren®

Film-coated tablets 20 mg: 28 or 56 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, round, biconvex, with a score on one side and an engraving “KE 20” on the other side.

Excipients: lactose monohydrate – 100 mg, microcrystalline cellulose – 113 mg, sodium carboxymethyl starch (type A) – 4 mg, colloidal silicon dioxide – 1.6 mg, magnesium stearate – 1.4 mg.

Shell composition hypromellose – 3.9 mg, titanium dioxide (E171) – 0.67 mg, macrogol 400 – 0.43 mg.

14 pcs. – blisters (2) – cardboard packs.
14 pcs. – blisters (4) – cardboard packs.

Clinical-Pharmacological Group

Beta₁-adrenergic blocker

Pharmacotherapeutic Group

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

Pharmacological Action

Selective beta₁-adrenergic blocker. Betaxolol is characterized by three pharmacological properties: cardioselective beta₁-adrenergic blocking action; absence of partial agonistic activity (absence of intrinsic sympathomimetic activity); weak membrane-stabilizing action (similar to the action of quinidine or local anesthetics) at concentrations exceeding therapeutic ones.

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

When betaxolol is used, its β₁-adrenoceptor blocking activity is manifested by the following pharmacodynamic effects:

• Decrease in heart rate at rest and during physical exertion (due to blockade of beta-adrenoceptors in the sinus node, which, in combination with the absence of intrinsic sympathomimetic activity in betaxolol, leads to a slowing of sinus node automaticity);
• Decrease in cardiac output at rest and during physical exertion due to competitive antagonism with catecholamines at peripheral (especially cardiac) adrenergic nerve endings;
• Decrease in 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 a 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 can slow AV node conduction.

Pharmacokinetics

Absorption

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 among different patients or in the same patient during long-term use have minor variations, which is associated with the high bioavailability of betaxolol.

Distribution

Betaxolol binds to blood 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 – about 6 L/kg. Fat solubility is moderate.

Metabolism

Betaxolol is metabolized in the liver to form inactive metabolites.

Elimination

It is excreted by the kidneys in the form of metabolites (more than 80%), 10-15% – unchanged. T_1/2 of betaxolol – 15-20 hours.

Pharmacokinetics in special clinical cases

T_1/2 in case of impaired liver function is prolonged by 33%, but clearance does not change; in case of impaired renal function, T_1/2 doubles (dose reduction is necessary).

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

The drug is taken orally with a sufficient amount of liquid. The tablet should not be chewed.

The initial dose of Lokren^® for both indications for use of the drug is usually 10 mg (1/2 tab. 20 mg). If target blood pressure values are not achieved within 7-14 days of treatment, the dose is doubled to 20 mg/day.

Doses of Lokren^® exceeding 20 mg are usually not used (due to the fact that when the dose is increased above 20 mg, no statistically significant increase in the antihypertensive effect of the drug is observed).

The maximum daily dose of Lokren^® is 40 mg.

In patients with renal insufficiency, dose adjustment is recommended depending on the patient’s renal functional status. For CrCl greater than 20 ml/min, no dose adjustment is required. However, at the beginning of treatment, clinical monitoring is recommended until the steady-state concentration of the drug in the blood is reached (which is achieved on average by the 4th-7th day of treatment). In cases of severe renal insufficiency ( CrCl less than 20 ml/min), the recommended initial dose of the drug is 5 mg/day (regardless of the frequency and days of hemodialysis procedure in patients on hemodialysis), which, if insufficiently effective, can be doubled every 1-2 weeks. The maximum daily dose is 20 mg.

In patients with hepatic insufficiency, dose adjustment is usually not required. However, at the beginning of therapy, more careful clinical monitoring of the patient is recommended.

Adverse Reactions

Allergic reactions skin rash, itching, urticaria.

The adverse effects listed below are given according to the following frequency gradations: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000) (including isolated reports).

Dermatological reactions rare – various skin reactions, including skin rash, itching, urticaria, psoriasiform eruptions or exacerbation of psoriasis.

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

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

Gastrointestinal disorders common – stomach pain, diarrhea, nausea, vomiting.

Metabolism and nutrition disorders very rare – hypoglycemia, hyperglycemia.

Cardiac and vascular disorders common – bradycardia, possibly severe, decrease in skin temperature of the upper and lower extremities; rare – 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 rare – bronchospasm.

Reproductive system and breast disorders: common – impotence.

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

Effects on the fetus intrauterine growth retardation, hypoglycemia, bradycardia.

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

Contraindications

• Severe forms of bronchial asthma and chronic obstructive pulmonary disease;
• 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 obliterating peripheral arterial diseases;
• Pheochromocytoma without simultaneous use of alpha-blockers;
• Arterial hypotension (systolic BP <100 mm Hg);
• History of anaphylactic reactions;
• Metabolic acidosis;
• Cardiomegaly (without signs of heart failure);
• Simultaneous use with sultopride and floctafenine;
• Concomitant use of MAO inhibitors;
• Children and adolescents under 18 years of age (efficacy and safety not established);
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption (due to the presence of lactose in the drug composition);
• Hypersensitivity to betaxolol and excipients of the drug.

With caution the drug should be used

• In bronchial asthma and chronic obstructive pulmonary disease of moderate severity (start treatment with small doses and preferably under the control of external respiratory function parameters; due to the beta₁-selectivity of betaxolol, if an asthma attack occurs during its use, it is possible to stop the attack with beta₂-adrenergic agonists);
• In chronic heart failure in the compensation stage (treatment with betaxolol is possible only under strict medical supervision; treatment should be started with very small doses with their gradual increase);
• In AV block I degree (careful observation, including ECG monitoring, is required);
• In obliterating peripheral arterial diseases, Raynaud’s syndrome (except for severe form) (increased peripheral circulatory disorders are possible);
• In Prinzmetal’s angina (increased frequency of angina attacks is possible; the use of a selective beta₁-adrenergic blocker is possible only with simultaneous use of vasodilators);
• In treated pheochromocytoma (when treating arterial hypertension with Lokren^® against the background of treated pheochromocytoma, careful monitoring of blood pressure parameters is required);
• In elderly patients (treatment should be started with small doses and under careful medical supervision);
• In renal insufficiency (with CrCl greater than 20 ml/min – careful monitoring of the patient during the first 4 days of treatment; with CrCl less than 20 ml/min and/or undergoing hemodialysis, dosage regimen adjustment is required);
• In hepatic insufficiency (more careful clinical monitoring is required at the beginning of treatment);
• In patients with diabetes mellitus (regular monitoring of blood glucose concentration, including active self-monitoring by the patient, is necessary at the beginning of treatment; a decrease in the severity of precursors of hypoglycemia, such as tachycardia, palpitations and increased sweating, is possible);
• In psoriasis (beta-blockers may worsen the course of psoriasis);
• When conducting desensitizing therapy.

Use in Pregnancy and Lactation

Pregnancy

In experimental studies, no teratogenic effect of betaxolol was detected.

To date, no teratogenic effects in humans have been reported.

As a rule, beta-blockers reduce blood flow in the placenta and can affect fetal development. Blood flow in the placenta and uterus should be monitored, and the growth and development of the unborn child should be observed, and in case of adverse events regarding pregnancy and/or the fetus, alternative therapeutic measures should be taken.

The newborn should be carefully examined after delivery. In the first 3-5 days of life, symptoms of bradycardia and hypoglycemia may occur, as the effect of beta-blockers in newborns whose mothers took them before delivery persists for several days after birth. In the neonatal and postnatal period, newborns have an increased risk of cardiac and respiratory complications. In case of heart failure, hospitalization of the newborn in the intensive care unit is required. The use of plasma substitutes should be avoided (risk of acute pulmonary edema). Bradycardia, respiratory failure and hypoglycemia have also been reported. In this regard, during the first 3-5 days of life, careful monitoring of such newborns in a specialized department is required (heart rate, blood glucose concentration).

In this regard, the use of Lokren^® during pregnancy is not recommended and is possible only if the benefit to the mother outweighs the potential risk to the fetus or child.

Lactation period

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 (more careful clinical monitoring is required at the beginning of treatment).

Use in Renal Impairment

Use with caution in renal insufficiency (with CrCl greater than 20 ml/min – careful monitoring of the patient during the first 4 days of treatment; with CrCl less than 20 ml/min and/or undergoing hemodialysis, dosage regimen adjustment is required.

Pediatric Use

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

Geriatric Use

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

Special Precautions

Treatment with Lokren^® should not be interrupted abruptly and the recommended dose should not be changed without prior consultation with a doctor, as this may lead to a temporary deterioration in 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 Lokren^®, 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 (once every 4-5 months), renal function in elderly patients (once every 4-5 months).

The patient should be taught the method of counting heart rate, and the patient should be instructed to consult a doctor if the heart rate decreases to less than 50 beats/min.

Approximately 20% of patients with angina do not respond to beta-blockers. The main reasons are severe coronary atherosclerosis with a low ischemia threshold (heart rate at the moment of angina attack is less than 100 beats/min) and increased left ventricular end-diastolic pressure, impairing subendocardial blood flow.

When clonidine is taken simultaneously, its administration can be discontinued only several days after discontinuation of Lokren^®.

Lokren^® 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.

Bronchial asthma and chronic obstructive pulmonary disease

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

If attacks develop during treatment, bronchodilators – beta₂-adrenergic agonists – can be used.

Heart failure

In patients with heart failure controlled therapeutically, if necessary, Betaxolol can be used under strict medical supervision at very low initial doses with their gradual increase if necessary and in case of good tolerance (preservation of compensated state of chronic heart failure).

Bradycardia

If the resting heart rate falls below 50-55 beats/min, the dose of Lokren^® should be reduced.

First-degree AV block

Given the negative dromotropic effect of beta-blockers, the drug should be used with caution in first-degree block.

Prinzmetal’s angina

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.

Peripheral circulatory disorders

Beta-blockers may worsen the condition of patients with peripheral circulatory disorders (Raynaud’s disease or Raynaud’s syndrome, arteritis, or chronic obliterating arterial diseases of the lower extremities).

Pheochromocytoma

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

Elderly patients

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

Patients with renal insufficiency

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

Patients with diabetes mellitus

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.

Psoriasis

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

Allergic reactions

Beta-blockers, including Lokren^®, 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 provide the expected therapeutic effect.

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

General anesthesia

During general anesthesia, the risk of beta-adrenergic receptor blockade (decreased heart rate, reduced 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 beta-blocker treatment.

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

Beta-blocker therapy may not be discontinued in some cases

• In patients with coronary insufficiency, it is advisable to continue treatment up until surgery, considering the risk associated with abrupt withdrawal of beta-blockers;
• In case of emergency surgeries or when discontinuation of treatment is impossible, the patient should be protected from the consequences of vagus nerve excitation by appropriate premedication with atropine, repeated if necessary.

In such patients, substances that depress the myocardium the least should be used for general anesthesia, and blood loss should be replenished.

The risk of developing anaphylactic reactions must be considered.

Thyrotoxicosis

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

Athletes

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 be aware that treatment with beta-blockers may reduce tear fluid production.

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

Effect on ability to drive vehicles and operate machinery

Caution should be exercised when driving vehicles or engaging in other potentially hazardous activities while taking Lokren^® (due to the risk of dizziness and weakness, which may reduce attention and the speed of psychomotor reactions required for these activities).

Overdose

Symptoms pronounced bradycardia, dizziness, AV block, pronounced decrease in blood pressure, arrhythmias, ventricular extrasystole, fainting, heart failure, difficulty breathing, bronchospasm, cyanosis of fingernails and palms, convulsions.

Treatment gastric lavage, administration of adsorbents; in case of bradycardia development, atropine 1-2 mg IV is recommended; then (if necessary) slow infusion of 25 mcg isoprenaline or infusion of dobutamine 2.5-10 mcg/kg/min; sometimes temporary pacemaker placement may be required; in case of excessive blood pressure decrease, IV administration of plasma-substituting solutions and vasopressor drugs is recommended; for bronchospasm – administration of bronchodilators, including beta₂-adrenomimetics and/or aminophylline; in case of heart failure (decompensation) in newborns whose mothers took beta-blockers during pregnancy, hospitalization in the intensive care unit is recommended, isoprenaline and dobutamine – long-term and usually in high doses, specialist supervision.

Drug Interactions

Contraindicated combinations

With floctafenine

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

With sultopride

Disturbances of cardiac automaticity (pronounced bradycardia) due to additional decrease in heart rate.

Not recommended combinations

With amiodarone

Disturbances of contractility, automaticity and conduction (suppression of sympathetic compensatory mechanisms).

With slow calcium channel blockers (bepridil, diltiazem and verapamil)

Disturbances of automaticity (pronounced bradycardia, sinus arrest), disturbances of AV conduction, heart failure (synergistic /mutually reinforcing/ effects).

This combination can only be used under careful clinical and ECG monitoring, especially in elderly patients or at the beginning of treatment.

With cardiac glycosides

Risk of development or worsening of bradycardia, AV block, cardiac arrest.

With MAO inhibitors

Concomitant use with MAO inhibitors is not recommended due to significant enhancement of the antihypertensive effect of betaxolol; the treatment interval between MAO inhibitor and betaxolol intake should be at least 14 days.

With iodine-containing contrast agents

In case of shock or sharp decrease in blood pressure upon administration of iodine-containing contrast agents, beta-blockers reduce compensatory cardiovascular reactions. If possible, beta-blocker treatment should be discontinued before radiographic examination using iodine-containing contrast agents.

Combinations requiring caution

With inhalational halogen-containing anesthetics

Beta-blockers have a cardiodepressant effect (inhibition of β-adrenergic receptors may be reduced by administration of beta-adrenergic stimulants). As a rule, beta-blocker treatment 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 rhythm disturbances, including torsades de pointes ventricular tachycardia: class IA antiarrhythmics (quinidine, hydroquinidine and disopyramide) and class III (amiodarone, dofetilide, ibutilide), sotalol, some phenothiazine group neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine), benzamides (amisulpride, sulpiride, tiapride), butyrophenones (droperidol, haloperidol), other neuroleptics (pimozide) and other drugs (cisapride, diphemanil, IV erythromycin, halofantrine, mizolastine, moxifloxacin, pentamidine, IV spiramycin and IV vincamine

Increased risk of ventricular rhythm disturbances, particularly 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 if necessary is 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, disturbances of AV conduction. 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 conducted.

With lidocaine 10% solution (IV as an antiarrhythmic agent)

Increase in plasma lidocaine concentration with possible increase in adverse neurological symptoms and cardiovascular effects (decreased lidocaine metabolism in the liver). Clinical and ECG monitoring and, possibly, monitoring of plasma lidocaine concentration during beta-blocker treatment and after its discontinuation is recommended. If necessary – adjustment of the lidocaine dose.

Combinations to be taken into account

With NSAIDs (systemically acting drugs), including selective COX-2 inhibitors

Reduction of the antihypertensive effect of betaxolol (inhibition of prostaglandin synthesis by NSAIDs and retention of water and sodium 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 heart failure or uncontrolled heart failure. Beta-blocker treatment may minimize the reflex activation of the sympathetic nervous system in response to vasodilation under the influence of slow calcium channel blockers from the dihydropyridine group.

With tricyclic antidepressants (imipramine type), neuroleptics

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 cardiodepressant action and likelihood of blood pressure decrease.

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., under the influence of 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 decrease 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 circulatory disorders when taking betaxolol.

Storage Conditions

The drug should be stored out of the reach of children at a temperature below 25°C (77°F).

Shelf Life

The shelf life is 5 years.

Dispensing Status

The drug is dispensed by prescription.

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.