Pharmacological properties of the drug Betaxolol
betaxolol (( RS )-l-[4-[2-(cyclopropylmethoxy)ethyl]phenoxy]-3-[(1-methylethyl)amino]-2-propan-2-ol) is a selective β1-adrenergic receptor blocker. Due to the cardioselective β-adrenergic blocking effect, it causes a decrease in blood pressure, a decrease in heart rate and a decrease in oxygen consumption by the myocardium. These effects are accompanied by weak negative inotropic and dromotropic effects. At recommended doses, betaxolol does not exhibit partial agonist activity (that is, it does not have BCA) and a membrane-stabilizing effect. Betaxolol reduces serum renin and aldosterone levels. Quickly and completely absorbed after oral administration. The effect of the first passage through the liver is insignificant, bioavailability is about 85%. Approximately 50% of betaxolol binds to plasma proteins. The volume of distribution is approximately 6 l/kg. In the body, betaxolol is mainly converted into inactive metabolites and only 10–15% is excreted unchanged in the urine. The half-life is 15–20 hours. When betaxolol solution is instilled into the eye, increased intraocular pressure is reduced by reducing the production of intraocular fluid. Betaxolol has high lipophilicity, which creates high concentrations of the drug in the tissues of the eye. It begins to act within 30 minutes, and the maximum effect is usually achieved 2 hours after topical application. The duration of reduction in intraocular pressure after a single use is 12 hours.
Use of the drug Betaxolol
Usually prescribed at a dose of 20 mg 1 time per day, however, in some patients, betaxolol is effective at a daily dose of 10 mg. For angina pectoris, the daily dose, if necessary, can be increased to 40 mg. In patients with renal failure with creatinine clearance ≥20 ml/min, no dose adjustment is required. With a creatinine clearance of 20 ml/min and in patients undergoing dialysis, the recommended initial dose is 5 mg/day (regardless of the frequency of dialysis procedures). If the expected effect is not achieved, the dose can be increased by 5 mg/day every 2 weeks to a maximum dose of 20 mg/day. In patients with insufficient liver function, there is no need for dose adjustment, however, clinical observation is advisable at the beginning of therapy. It is recommended to reduce the initial dose to 5 mg in elderly patients, especially those prone to bradycardia. In ophthalmology, adults (including elderly patients) are prescribed 1–2 drops of 0.25% solution into the affected eye(s) 2 times a day. In some patients, it may take several weeks for the antihypertensive effect to stabilize.
Side effects of the drug Betaxolol
Asthenia, cold extremities, bradycardia (sometimes severe), abdominal pain, nausea, vomiting, impotence, dizziness, headache, insomnia, rarely - slowing of AV conduction or progression of existing AV blockade, heart failure, arterial hypotension, bronchospasm, hypoglycemia , Raynaud's syndrome, increased intermittent claudication, skin reactions, including psoriasis-like rashes or exacerbation of psoriasis, depression. In rare cases, the appearance of antinuclear antibodies is observed, which in exceptional cases is accompanied by clinical manifestations such as systemic lupus erythematosus, which disappear after discontinuation of betaxolol. Local reactions when using eye drops: immediately after instillation, short-term discomfort in the eyes is possible. Sometimes - punctate keratitis, photophobia, lacrimation, itching, dry eyes, eye pain, decreased visual acuity, allergic reactions, decreased sensitivity of the cornea, edema and anisocoria.
Betaxolol-SOLOpharm eye drops 0.5% dropper bottle 5 ml 1 pc. in Moscow
Latin name
BETAXOLOL-SOLOpharm
International nonproprietary name
Betaxolol
Release form
Eye drops
Package
5 ml - polyethylene dropper bottle (1) - cardboard packs.
Description
Eye drops in the form of a clear, colorless or light yellow liquid.
pharmachologic effect
Cardioselective beta1-blocker without intrinsic sympathomimetic activity. Has weak membrane stabilizing activity. It has a hypotensive effect associated with a decrease in cardiac output and a decrease in sympathetic stimulation of peripheral vessels. When used in therapeutic doses, it does not have a cardiodepressive effect, does not affect glucose metabolism, does not reduce the bronchodilatory effect of beta-adrenergic agonists, and does not cause sodium ion retention in the body. Lasts for a long time.
When applied topically in the form of eye drops, it reduces elevated intraocular pressure. The resorptive effect is slightly expressed.
Indications
For systemic use: as monotherapy and as part of combination therapy - arterial hypertension, prevention of angina attacks.
For local use in ophthalmology: chronic open-angle glaucoma, increased intraocular pressure, condition after laser trabeculoplasty.
Directions for use and doses
For systemic use when taken orally - 20 mg 1 time / day. For patients on continuous hemodialysis or peritoneal dialysis, the initial dose is 10 mg/day; The time for taking betaxolol is set regardless of the mode of dialysis sessions.
For local use in ophthalmology - 1 drop 2 times a day into the affected eye. During the first month, therapy is carried out under the control of the level of intraocular pressure; subsequently, the frequency of measuring intraocular pressure is determined individually. If betaxolol is used after previous treatment with another similar drug, the dosage regimen is determined individually.
Compound
1 ml: betaxolol hydrochloride 5.6 mg, which corresponds to the content of betaxolol 5 mg. Excipients: benzalkonium chloride - 0.1 mg, sodium chloride - 5.49 mg, disodium phosphate dihydrate - 3.579 mg, disodium edetate (Trilon B) - 0.5 mg, sodium dihydrogen phosphate dihydrate - 3.165 mg, water for injection - up to 1 ml.
Contraindications
Cardiogenic shock; acute heart failure, chronic heart failure in the stage of decompensation, not compensated by treatment with diuretics, inotropes, ACE inhibitors, and other vasodilators; AV block II and III degrees (without an installed artificial pacemaker); Prinzmetal's angina (monotherapy is contraindicated); SSSU, sinoatrial block; severe bradycardia (heart rate less than 45-50 beats/min); severe peripheral circulatory disorders, severe forms of bronchial asthma and COPD; severe forms of Raynaud's disease and peripheral arterial occlusive disease; pheochromocytoma without simultaneous use of alpha-blockers; arterial hypotension (systolic blood pressure <100 mm Hg); history of anaphylactic reactions; metabolic acidosis; cardiomegaly (without signs of heart failure); simultaneous use with sultopride and floctafenine; simultaneous use of MAO inhibitors; children and adolescents up to 18 years of age; hypersensitivity to betaxolol.
Use during pregnancy and breastfeeding
During pregnancy and lactation (breastfeeding), the use of betaxolol is possible only in cases where the expected benefit to the mother outweighs the possible risk to the fetus or child.
special instructions
It should be used with caution in case of bronchial asthma and moderate COPD (start treatment with small doses and preferably under the control of respiratory function indicators; due to the beta1-selectivity of betaxolol, if an attack of bronchial asthma occurs while taking it, it is possible to relieve the attack with beta2-adrenergic agonists); in case of chronic heart failure in the compensation stage (treatment with betaxolol is possible only under strict medical supervision; treatment should begin with very small doses with a gradual increase); with AV blockade of the first degree (careful monitoring is required, including ECG monitoring); with obliterating diseases of peripheral arteries, Raynaud's syndrome (with the exception of severe forms) (possible increase in peripheral circulatory disorders); with Prinzmetal's angina (possible increased frequency of angina attacks; the use of a selective beta1-blocker is possible only with the simultaneous use of vasodilators); with treated pheochromocytoma (careful monitoring of blood pressure levels is required); in elderly patients (treatment should be started with small doses and under close medical supervision); in case of renal failure (with CC more than 20 ml/min - careful monitoring of the patient during the first few days of treatment; with CC less than 20 ml/min and/or hemodialysis, adjustment of the dosage regimen is required); with liver failure (more careful clinical monitoring is required at the beginning of treatment); in patients with diabetes mellitus (regular monitoring of blood glucose concentrations is required, including active self-monitoring by the patient at the beginning of treatment; it is possible to reduce the severity of precursors of hypoglycemia, such as tachycardia, palpitations and increased sweating); for psoriasis (beta-blockers can worsen the course of psoriasis); during desensitizing therapy.
Betaxolol should be discontinued gradually, especially in patients suffering from coronary artery disease and angina pectoris.
Betaxolol does not affect the size of the pupil, therefore, in case of angle-closure glaucoma, the drug should be used only in combination with miotics. When transferring a patient to betaxolol after treatment with several antiglaucoma drugs, the latter are discontinued gradually, over a period of at least 1 week per drug.
With the simultaneous use of betaxolol in the form of eye drops and beta-blockers orally, additive effects may develop both on the part of intraocular pressure and manifestations of the systemic action of beta-blockers.
Before a planned operation, beta-blockers, incl. betaxolol should be discontinued.
When using betaxolol topically, you should not wear contact lenses.
It is not recommended to use betaxolol in children.
Impact on the ability to drive vehicles and operate machinery
Use with caution in patients whose activities require increased attention and rapid psychomotor reactions.
Side effects
From the cardiovascular system: at the beginning of treatment - AV block, sinus bradycardia, arterial hypotension, heart failure, Raynaud's syndrome.
From the digestive system: rarely - abdominal pain, nausea, vomiting.
From the central nervous system and peripheral nervous system: at the beginning of treatment - asthenia, paresthesia of the extremities, sleep disturbances, depression, drowsiness, dizziness.
From the respiratory system: rarely - bronchospasm.
Allergic reactions: rarely - psoriasis-like skin manifestations.
Local reactions: when used in the form of eye drops immediately after instillation, short-term discomfort in the eyes and sometimes lacrimation are possible; rarely - decreased sensitivity of the cornea, erythema, itching, spotty coloration of the cornea, keratitis, anisocoria, photophobia.
Drug interactions
When used simultaneously with adrenergic agonists and xanthine derivatives, the effectiveness of betaxolol decreases.
When used simultaneously with antacids and antidiarrheals, the absorption of beta-blockers may be reduced.
When used simultaneously with antihypertensive drugs, the antihypertensive effect is enhanced.
With the simultaneous use of halogen-containing agents for inhalation anesthesia, the negative inotropic effect may be enhanced.
With simultaneous use of non-depolarizing muscle relaxants, their duration of action may be increased.
With the simultaneous use of NSAIDs and corticosteroids, the antihypertensive effect of betaxolol decreases.
With simultaneous use of cardiac glycosides, bradycardia may increase.
With the simultaneous use of tricyclic antidepressants (imipramine), blood pressure decreases and there is a risk of developing orthostatic hypotension.
With the simultaneous use of amiodarone, verapamil, diltiazem, beta-blockers for topical use in glaucoma, increased negative inotropic effects and conduction disturbances are possible.
With simultaneous use of lidocaine, the concentration of lidocaine in the blood plasma increases.
When used simultaneously with drugs that deplete catecholamine reserves (including reserpine), the hypotensive effect and bradycardia may be enhanced.
When used simultaneously with sulfasalazine, the concentration of betaxolol in the blood plasma increases.
Storage conditions
At a temperature not higher than 25 degrees.
Special instructions for the use of Betaxolol
Treatment should not be stopped abruptly. Abrupt withdrawal of betaxolol in patients with coronary artery disease may result in severe cardiac arrhythmias, myocardial infarction, or sudden death. The dose of betaxolol should be reduced gradually over 1–2 weeks while starting therapy with another drug. β1-adrenergic blockers for COPD can be prescribed only to patients with moderate disease at a low initial dose. Before starting treatment, it is recommended to assess respiratory function. If bronchospasm develops during treatment, β2-adrenergic agonists are prescribed. In patients with compensated heart failure, betaxolol is prescribed in low initial doses. In the future, if necessary, they are gradually increased under strict medical supervision. The dose of betaxolol should be reduced if the resting heart rate is below 50–55 beats/min. Given the negative dromotropic effect of β-adrenergic receptor blockers, betaxolol is used with caution in patients with first-degree AV block. The use of β-adrenergic receptor blockers can lead to a deterioration in the condition of patients with peripheral circulatory disorders (Raynaud's disease or syndrome, arteritis, chronic occlusive diseases of the arteries of the lower extremities). When β-adrenergic blockers are used in combination with α-adrenergic blockers for the treatment of symptomatic hypertension (arterial hypertension) in pheochromocytoma, careful monitoring of blood pressure is required. In patients with diabetes mellitus, betaxolol can mask the symptoms of hypoglycemia (tachycardia, palpitations, sweating). Prescribed with caution to patients with psoriasis, as there are reports of exacerbation of the disease during treatment with β-adrenergic receptor blockers. In patients with a predisposition to severe allergic reactions, especially those caused by the use of iodinated contrast agents or floctafenine, or when undergoing specific desensitization, therapy with beta-adrenergic blockers may lead to the development of severe anaphylactic reactions and a decrease in the effectiveness of epinephrine in normal doses. During anesthesia, β-adrenergic receptor blockers suppress reflex tachycardia and increase the risk of developing arterial hypotension. The anesthesiologist should be informed that the patient is taking a β-adrenergic blocker. If anesthesia is necessary, it is recommended to discontinue the use of betaxolol 48 hours before surgery (this time is sufficient to restore the sensitivity of β-adrenergic receptors to catecholamines). Therapy with β-adrenergic blockers should not be interrupted in patients with coronary insufficiency; it is advisable to continue treatment until surgery, taking into account the risk associated with the development of withdrawal syndrome. In the case of urgent operations, the patient is prescribed premedication with atropine to prevent stimulation of the vagus nerve, and its administration is repeated if necessary. For anesthesia, it is necessary to use agents with minimal cardiodepressive effect. The use of beta-adrenergic blockers reduces intraocular pressure and may affect test results for glaucoma. Patients receiving systemic and local treatment with beta-blockers should be closely monitored due to the possibility of additive effects. β-adrenergic receptor blockers mask the cardiac symptoms of thyrotoxicosis. Betaxolol may give a positive reaction in doping control tests. Betaxolol is not recommended for use during pregnancy. Newborns whose mothers took β-adrenergic blockers may experience bradycardia, respiratory distress syndrome and hypoglycemia, so careful monitoring of newborns in a specialized department is recommended (monitoring heart rate and serum glucose levels during the first 3–5 days of life). β-adrenergic blockers pass into breast milk, so it is recommended to stop breastfeeding during their use.
Betaxolol
Contraindicated combinations
With floctafenine
In case of shock or arterial hypotension caused by floctafenine, β-blockers cause a decrease in compensatory cardiovascular reactions.
With sultopride
Violations of heart automaticity (severe bradycardia) due to an additional effect that induces the development of bradycardia.
Combinations not recommended
With amiodarone
Violations of contractility, automaticity and conductivity (suppression of sympathetic compensatory mechanisms).
With cardiac glycosides
Risk of developing or worsening bradycardia, atrioventricular block, cardiac arrest.
With MAO inhibitors
Concomitant use with MAO inhibitors is not recommended due to a significant increase in the antihypertensive effect of betaxolol; the interval between taking MAO inhibitors and betaxolol should be at least 14 days.
With fingolimod
Fingolimod may enhance the negative chronotropic effect of beta-blockers and lead to severe bradycardia. Concomitant use of fingolimod and betaxolol is not recommended. If it is necessary to use these drugs simultaneously, careful monitoring of the patient's condition is required. It is recommended to initiate combination therapy in a hospital setting and carry out appropriate monitoring (long-term heart rate monitoring is indicated, at least until the morning of the next day after the first simultaneous administration of fingolimod and a beta-blocker).
Combinations to use with caution
With blockers of “slow” calcium channels (diltiazem and verapamil)
Automatic disorders (severe bradycardia, sinus node arrest), atrioventricular conduction disorders, heart failure [synergistic (mutually reinforcing) effects].
This combination should only be used under close clinical and electrocardiographic supervision, especially in elderly patients or at the beginning of treatment.
With diltiazem
An increased risk of depression has been reported when β-blockers are used concomitantly with diltiazem.
With iodinated contrast agents
In the event of shock or a sharp decrease in blood pressure with the introduction of iodine-containing contrast agents, β-blockers reduce compensatory cardiovascular reactions. If possible, beta-blocker treatment should be discontinued before radiographic examinations using iodinated contrast media are performed. If it is necessary to continue therapy with a beta-blocker, the physician must provide appropriate conditions for intensive care.
With inhaled halogenated anesthetics
β-blockers reduce compensatory cardiovascular responses (inhibition of β-adrenergic receptors can be reduced with the administration of β-adrenergic agonists). As a rule, treatment with beta-blockers is not discontinued and in any case abrupt discontinuation of beta-blockers should be avoided. The anesthesiologist must be informed about taking a β-blocker.
With drugs that can cause ventricular arrhythmias, including polymorphic ventricular tachycardia of the “pirouette” type
Increased risk of ventricular arrhythmias, in particular polymorphic ventricular tachycardia of the “pirouette” type, with simultaneous use of betaxolol with drugs such as:
- class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, procainamide);
- class III antiarrhythmic drugs (amiodarone, dofetilide, ibutilide, bretylium tosylate, dronedarone), sotalol;
- other (non-antiarrhythmic) medicines, such as:
- neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, tiapride), butyrophenones (droperidol, haloperidol);
- other antipsychotics (pimozide, sertindole);
- antidepressants: tricyclic antidepressants, selective serotonin reuptake inhibitors (citalopram, escitalopram);
- antibacterial agents: fluoroquinolones (levofloxacin, moxifloxacin, sparfloxacin, ciprofloxacin), macrolides (erythromycin for intravenous administration, spiramycin for intravenous administration, azithromycin, clarithromycin, roxithromycin), co-trimoxazole;
- antifungals: azoles (voriconazole, itraconazole, ketoconazole, fluconazole); antimalarials (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); antiprotozoal drugs (pentamidine when administered intravenously);
- antianginal agents (ranolazine);
- antitumor agents (vandetanib, arsenic trioxide, oxaliplatin, tacrolimus);
- antiemetics (domperidone, ondansetron);
- drugs affecting gastrointestinal motility (cisapride);
- antihistamines (astemizole, terfenadine, mizolastine);
- other drugs (anagrelide, vasopressin, difemanil methyl sulfate, ketanserin, probucol, propofol, sevoflurane, terlipressin, terodiline, flecainide, cilostazol).
When betaxolol is used concomitantly with these drugs, careful clinical and electrocardiographic monitoring is required.
With propafenone and class IA antiarrhythmics (quinidine, hydroquinidine and disopyramide)
Violations of contractility, automaticity and conductivity (suppression of sympathetic compensatory mechanisms). Clinical and electrocardiographic monitoring is required.
With baclofen
Strengthening the antihypertensive effect of betaxolol. Monitoring blood pressure and adjusting the dose of betaxolol if necessary is necessary.
With insulin and hypoglycemic agents for oral administration, sulfonylurea derivatives
(see sections “With caution”, “Side effects”, “Special instructions”)
All β-blockers may mask certain symptoms of hypoglycemia, such as palpitations and tachycardia.
The patient should be warned about the need to increase regular monitoring of blood glucose concentrations, including active self-monitoring by the patient, especially at the beginning of treatment.
With cholinesterase inhibitors (donepezil, galantamine, neostigmine, pyridostigmine, rivastigmine)
Risk of increased bradycardia (additive effect). Regular clinical monitoring is required.
With centrally acting antihypertensives (clonidine, α-methyldopa, guanfacine, moxonidine, rilmenidine)
Increased risk of developing bradycardia and atrioventricular conduction disorders. Significant increase in blood pressure upon abrupt discontinuation of a centrally acting antihypertensive drug. Abrupt withdrawal of antihypertensive drugs should be avoided and clinical monitoring should be carried out.
With lidocaine (10% solution, intravenously as an antiarrhythmic agent)
An increase in the concentration of lidocaine in the blood plasma with a possible increase in undesirable neurological symptoms and effects on the cardiovascular system (decreased metabolism of lidocaine in the liver). Clinical and electrocardiographic observation and, possibly, monitoring of lidocaine plasma concentrations during treatment with beta-blockers and after its cessation are recommended. If necessary, the dose of lidocaine is adjusted.
Combinations to Consider
With non-steroidal anti-inflammatory drugs (NSAIDs) (drugs with systemic action), including selective cyclooxygenase-2 (COX-2) inhibitors
Reduced antihypertensive effect of betaxolol (NSAIDs inhibit prostaglandin synthesis and, being pyrazolone derivatives, lead to water and sodium retention).
With blockers of “slow” calcium channels from the dihydropyridine group (nifedipine)
Mutual enhancement of the antihypertensive effect of slow calcium channel blockers and betaxolol, development of heart failure in patients with latent or uncontrolled heart failure. Treatment with β-blockers may also minimize reflex activation of the sympathetic nervous system in response to vasodilation caused by slow calcium channel blockers from the dihydropyridine group.
With tricyclic antidepressants (such as imipramine), antipsychotics
Increased antihypertensive effect of betaxolol and the risk of developing orthostatic hypotension (additive effect).
With mefloquine
Risk of developing bradycardia (additive effect).
With dipyridamole (intravenous administration)
Strengthening the antihypertensive effect of betaxolol.
With α-blockers, including those used in urology (alfuzosin, doxazosin, prazosin, tamsulosin, terazosin)
Strengthening the antihypertensive effect of betaxolol. Increased risk of orthostatic hypotension.
With amifostine
Strengthening the antihypertensive effect of betaxolol.
With allergens used for immunotherapy or allergen extracts for skin testing
Increased risk of severe systemic allergic reactions or anaphylaxis in patients receiving betaxolol.
With phenytoin (intravenous administration)
Increased severity of cardiodepressive effects and the likelihood of lowering blood pressure.
With xanthines
Betaxolol reduces the clearance of xanthines (except diphylline) and increases their concentration in the blood plasma, especially in patients with initially increased clearance of theophylline (for example, under the influence of smoking).
With estrogens
Weakening the antihypertensive effect of betaxolol (sodium and water retention).
With glucocorticosteroids and tetracosactide
Weakening the antihypertensive effect of betaxolol (due to sodium and water retention due to the action of glucocorticosteroids and tetracosactide).
With diuretics
An excessive decrease in blood pressure is possible.
With non-depolarizing muscle relaxants
Betaxolol prolongs the action of non-depolarizing muscle relaxants.
With coumarins
Strengthening the anticoagulant effect of coumarins.
With ethanol (alcohol), sedatives and hypnotics
Increased depression of the central nervous system.
With non-hydrogenated ergot alkaloids
Non-hydrogenated ergot alkaloids increase the risk of developing peripheral circulatory disorders when taking betaxolol.
With sympathomimetics
Risk of decreased effects of β-blockers.
With drugs that induce sinus arrest
Sinus node arrest is possible with the simultaneous use of β-blockers, including Betaxolol, with drugs that can cause sinus node arrest.
