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.
Betaxolol-SOLOpharm, 0.5%, eye drops, 5 ml, 1 pc.
Diabetes
Beta-blockers should be prescribed with caution to patients with a tendency to spontaneous hypoglycemia and patients with labile diabetes mellitus, since these drugs may mask the signs and symptoms of acute hypoglycemia.
Thyrotoxicosis
Beta blockers may mask some symptoms of hyperthyroidism (eg, tachycardia). In patients with suspected thyrotoxicosis, beta-blockers should not be abruptly discontinued, as this may cause an increase in symptoms.
Myasthenia gravis
Beta blockers may cause symptoms and signs similar to those of myasthenia gravis (eg, diplopia, ptosis, general weakness).
Surgery
The anesthesiologist must be informed that the patient is taking betaxolol. Before a planned operation, beta-blockers should be gradually (not all at once!) withdrawn 48 hours before general anesthesia, because during general anesthesia, they can reduce the sensitivity of the myocardium to sympathetic stimulation necessary for cardiac function (for example, they can block the action of adrenaline).
Pulmonology
There have been reports of respiratory reactions, including death due to bronchospasm, in patients with bronchial asthma when using some beta-blockers in ophthalmology.
Betaxolol should be prescribed with caution to patients with moderate to moderate bronchial asthma (including a history of asthma), and to patients with mild to moderate chronic obstructive pulmonary disease.
Anaphylactic reactions
When betaxolol is used by patients with atopy or a history of severe anaphylactic reactions to various allergens, there may be a more pronounced reaction to repeated administration of these allergens and unresponsiveness to standard doses of epinephrine in relieving anaphylactic reactions.
Betaxolol should be used with caution in patients with severe peripheral circulatory disorders (i.e., patients with severe Raynaud's disease or Raynaud's syndrome, as well as pheochromocytoma).
When administered locally, beta-blockers can enter the systemic circulation and cause undesirable reactions from the cardiovascular, pulmonary and other systems.
Cases of severe respiratory and cardiovascular disorders, including death from bronchospasm in patients with bronchial asthma and death from heart failure, have been described when using betaxolol.
Heart disorders
In patients with cardiovascular disease (eg, coronary artery disease, Prinzmetal's angina, heart failure) and arterial hypotension, beta-blocker therapy should be critically evaluated with consideration of the possibility of treatment with drugs from other groups. Careful monitoring of the development of signs of exacerbation of the disease and adverse reactions in patients suffering from cardiovascular diseases is necessary.
Corneal diseases
Beta blockers may cause dry eyes. In patients with corneal diseases, the drug should be used with caution.
The main pathogenetic aspect of the treatment of angle-closure glaucoma is the need to open the anterior chamber angle, which is achieved by narrowing the pupil with the help of miotics. Betaxolol does not affect pupil diameter, therefore, in case of angle-closure glaucoma, the drug should be used only in combination with miotics.
Choroidal detachment
Cases of choroidal detachment have been described when using drugs that reduce the production of intraocular fluid (for example, timolol, acetazolamide) after fistulizing antiglaucomatous operations.
This product contains the preservative benzalkonium chloride, which may cause eye irritation and discoloration of soft contact lenses. Direct contact of the drug with soft contact lenses should be avoided. Patients using contact lenses should remove the lenses before using the drug and put them back no earlier than 15 minutes after instillation.
Impact on the ability to drive vehicles and machinery
During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
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.
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.
