Betaxolol

Pharmacological properties

betaxolol is characterized by three pharmacological properties: a cardioselective beta-blocking effect; lack of partial agonistic activity (that is, it does not exhibit its own sympathomimetic effect); weak membrane-stabilizing effect (like quinidine or local anesthetics) in concentrations exceeding the recommended therapeutic doses.

Pharmacokinetics Absorption. The drug is rapidly and completely absorbed after oral administration with a very small effect of the first passage through the liver and very high bioavailability - about 85%, which provides insignificant differences in its concentration in blood plasma in different patients or in one patient with prolonged use. Betaxolol binds to plasma proteins by approximately 50%.

Metabolism. The volume of distribution is about 6 l / kg body weight. In the body, betaxolol is mainly converted into inactive metabolites, and only 10-15% of betaxolol is determined in the urine unchanged. The main route of elimination is through the kidneys.

T_½ betaxolol from the body is 15–20 hours.

Indications

Ag, prevention of angina attacks.

Application

The usual dose is 1 tablet of 20 mg / day with antigens and for the prevention of angina attacks.

Dosage for patients with renal failure. In patients with renal failure, the clearance of betaxolol decreases with a decrease in renal function. The dose must be adapted to the condition of the patients kidneys: with creatinine clearance ≥20 ml / min, dose adjustment is not required. However, it is recommended to conduct clinical observation, starting from the 1st week of treatment until equilibrium levels of the drug in the blood are reached (on average 4 days).

For patients with severe renal failure (creatinine clearance of 20 ml / min), the recommended initial dose is 10 mg / day (regardless of the frequency and schedule of dialysis procedures in patients undergoing hemodialysis).

For patients with liver failure, there is no need for dose adjustment; however, clinical observation is desirable at the start of therapy.

Contraindications

• Severe forms of ba and hobble; decompensated heart failure; cardiogenic shock; av-block II – III degree in patients without pacemaker; prinzmetal angina (monotherapy is contraindicated in case of an isolated / typical form of this disease); sinus node dysfunction (including sinoatrial block); bradycardia (heart rate 45-50 beats / min); severe forms of Raynauds syndrome and other peripheral circulatory disorders; untreated pheochromocytoma; arterial hypotension; a history of anaphylactic reactions; metabolic acidosis; hypersensitivity to the components of the drug.

The drug is contraindicated for use in combination with flactafenin and sultopride. The use of the drug is not recommended in combination with amiodarone, bepridil, diltiazem and verapamil (see INTERACTIONS).

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

Side effects

On the part of the skin and subcutaneous tissue: skin reactions, including psoriasis-like rash or exacerbation of psoriasis (see special instructions); urticaria, itching, hyperhidrosis.

From the nervous system: dizziness, headache; distal paresthesia; lethargy.

From the side of the organ of vision: a feeling of dryness in the eyes, a violation of visual acuity.

From the psyche: asthenia, insomnia, fatigue; depression; nightmares, confusion, hallucinations.

From the digestive tract: gastrointestinal disorders (abdominal pain, diarrhea, nausea and vomiting).

From the side of metabolism and nutritional disorders: hypoglycemia, hyperglycemia, bradycardia (possibly severe); a slowdown in AV conduction or an increase in existing AV blockade, heart failure, and a decrease in blood pressure.

From the side of the vessels: cold extremities; Raynauds syndrome, worsening intermittent claudication.

From the respiratory system, chest and mediastinum: bronchospasm, dyspnea.

From the reproductive system: impotence.

Laboratory indicators. The occurrence of antinuclear antibodies is rarely observed, which only in exceptional cases was accompanied by clinical manifestations such as systemic lupus erythematosus, passing after the cessation of treatment.

special instructions

You should never suddenly stop the drug treatment in patients with angina pectoris: a sharp cessation of the drug can lead to serious heart rhythm disturbances, myocardial infarction, or sudden death.

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

Precautions for use. Drug withdrawal. Treatment with the drug should not be stopped suddenly, especially in patients with coronary artery disease. The dose must be reduced gradually, over 1-2 weeks, and if necessary, replacement therapy can be started at the same time to avoid the progression of angina pectoris.

BA and COPD. Β-adrenergic receptor blockers can only be prescribed to patients with a moderate degree of disease severity, with the choice of selective β-adrenergic receptor blockers in a low initial dose. Before starting treatment, an assessment of respiratory function is recommended. With the development of seizures during treatment, bronchodilators (β₂-adrenomimetics).

Heart failure. For the treatment of patients with non-refractory heart failure, the drug, if necessary, can be used with careful monitoring at low doses, which are gradually increased.

Bradycardia The dose must be reduced if the heart rate at rest is 50–55 beats / min and the clinical manifestations of bradycardia are noted in the patient.

AV block I degree. Given the negative dromotropic effect of β-adrenoreceptor blockers, Betacor is prescribed with caution in patients with degree I AV block.

Prinzmetals angina pectoris. The number and duration of angina attacks may increase with the use of β-adrenergic receptor blockers in patients with Prinzmetal angina. The use of the drug is possible for diseases of moderate severity and provided that the treatment is carried out simultaneously with the use of vasodilators.

Peripheral circulatory disorders. Blockers of β-adrenergic receptors can lead to a deterioration in the condition of patients with peripheral circulation disorders (Raynauds disease or Raynauds syndrome, arteritis or chronic obliterating diseases of the arteries of the lower extremities). In such cases, it is recommended to use a cardioselective β-adrenergic receptor blocker with the presence of the properties of a partial β-receptor agonist; it should be prescribed with caution.

Pheochromocytoma. When β-adrenoreceptor blockers are used to treat hypertension caused by pheochromocytoma, constant monitoring of blood pressure is required.

Patients of advanced age. In elderly patients, strict adherence to recommendations regarding contraindications is mandatory. Caution must be exercised: treatment of elderly patients should begin with a low dose and under close supervision (see APPLICATION).

Patients with renal failure. For patients with renal failure, the dosage must be adjusted depending on the concentration of creatinine in the blood or creatinine clearance (see APPLICATION).

Patients with diabetes.The patient should be warned about the need to strengthen self-monitoring of blood glucose levels at the beginning of treatment. Prodromal symptoms of hypoglycemia can be masked, especially tachycardia, palpitations and increased sweating (see INTERACTIONS AND SIDE EFFECTS).

Psoriasis. Prescribing a drug requires a thorough assessment of the need for its use, as there are reports of a deterioration in the condition of patients with psoriasis during treatment with β-adrenoreceptor blockers (see ADVERSE EFFECTS).

Allergic reactions. In patients prone to severe anaphylactic reactions, especially associated with the use of flactaphenin (see INTERACTIONS), or during desensitization, therapy with β-adrenergic receptor blockers can further enhance the reaction and reduce the effectiveness of treatment of this condition with conventional doses of epinephrine.

General anesthesia Β-adrenergic blockers cause a decrease in the severity of reflex tachycardia and increase the risk of arterial hypotension. Continued treatment with β-adrenoreceptor blockers reduces the risk of arrhythmia, myocardial ischemia and hypertensive crises. It is necessary to inform the anesthesiologist that the patient receives β-adrenergic receptor blockers. If necessary, discontinuation of treatment and discontinuation of the drug is considered sufficient 48 hours to restore sensitivity to catecholamines.

Therapy with β-adrenergic receptor blockers should not be stopped: in patients with coronary insufficiency who wish to take the drug before surgery, taking into account the risk associated with the sudden withdrawal of β-adrenergic receptor blockers; in case of urgent operations or in cases where the termination of treatment is impossible. The patient must be protected from the consequences of vagus nerve excitation by prescribing atropine sedation, with repetition if necessary. For anesthesia, drugs that depress the myocardium to the least extent should be used, and blood loss should be compensated.

The risk of anaphylactic reactions must be considered.

Ophthalmology. The blockade of β-adrenergic receptors causes a decrease in intraocular pressure and may lead to a change in the results of a screening study for glaucoma. An ophthalmologist should be informed that the patient is taking betaxolol. The condition of patients who receive β-adrenoreceptor blockers both systemically and in the form of eye drops should be monitored, taking into account the possible additive effect of these drugs.

Thyrotoxicosis. Β-adrenoreceptor blockers mask the cardiovascular symptoms of thyrotoxicosis.

Athletes. Athletes must consider that the drug contains an active substance that can give a positive reaction when conducting anti-doping control tests.

The drug contains lactose, so it should not be used in patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Use during pregnancy and lactation. Pregnancy. Teratogenic aspect. There are currently no reports of teratogenic effects in humans, or information on the identification of congenital malformations.

Neonatal aspect. The action of the β-adrenergic receptor blocker persists for several days after birth in infants whose mothers received treatment with this drug. Although this residual effect may not have clinical consequences, there is still a risk of heart failure. In this case, the newborn must be placed in the intensive care unit (see OVERDOSAGE), and the use of plasma substitutes should be avoided (due to the risk of developing acute pulmonary edema).There are also reports of cases of the development of bradycardia, respiratory distress syndrome and hypoglycemia. In this regard, careful monitoring of the newborn in specialized conditions (control of heart rate and blood glucose during the first 3-5 days of life) is recommended.

In this regard, the use of betaxolol during pregnancy is not recommended, unless the benefit of using the drug exceeds the possible risks.

Lactation. Β-adrenergic blockers pass into breast milk. Breastfeeding during the treatment with the drug should be discontinued, since the risk of developing hypoglycemia or bradycardia in newborns has not been investigated.

Children. The safety and effectiveness of the drug in children have not been established, therefore, its use in this category of patients is contraindicated.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Studies to study the effect of betaxolol on the ability to drive vehicles have not been conducted. When driving or working with other mechanisms, it is necessary to take into account that dizziness, visual impairment and other adverse reactions can sometimes occur while taking this drug, which can negatively affect the reaction rate when driving vehicles or other mechanisms.

Interactions

Bradycardia can be caused by a number of drugs: β-adrenoreceptor blockers, class Ia antiarrhythmic drugs (quinidine, disopyramide), class III (amiodarone and sotalol), class iv (diltiazem and verapamil), and digitalis glycosides, clonidine, guaflocin, and cholinesterase inhibitors used to treat Alzheimers disease.

Concomitant use with the following drugs is contraindicated.

Floktafenin. In case of shock or arterial hypotension due to flactaphenin, β-adrenergic blockers cause a decrease in compensatory cardiovascular reactions.

Suloprid. Violations of the automatism of the heart (excessive bradycardia), due to the additive effect of reducing heart rate.

It is not recommended to use the drug with the following drugs.

Calcium channel blockers (bepridil, diltiazem and verapamil). Disorders of automatism (excessive bradycardia, sinus node stop), AV conduction, heart failure (synergistic effect). Such combinations can only be used with careful clinical monitoring and ECG monitoring, especially in elderly patients or at the beginning of treatment.

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

Use with caution with the following drugs.

Halogen inhaled anesthetics. Β-adrenoreceptor blockers cause a decrease in cardiovascular compensatory reactions (during surgery, inhibition of β-adrenoreceptor blockers can be eliminated by β-stimulants). As a rule, therapy with β-adrenergic receptor blockers should not be discontinued, and abrupt withdrawal of the drug should be avoided in any case. It is necessary to inform the anesthetist about the treatment.

Drugs that can provoke atrial fibrillation (except suloprid)

Antiarrhythmic drugs of class Ia (quinidine, hydroquinidine and disopyramide) and class III (amiodarone, dofetilide, ibutilide, sotatol); some antipsychotics of the phenothiazine group (chlorpromazine, cyamemazine, levomepromazine, thioridazine), benzamides (amisulpride, sulpiride, tiapride), butyrophenones (droperidol, haloperidol), other antipsychotics (pimozide), and other drugs (virimeridine, diaziridiride, cifiryridin misolastine, moxifloxacin, pentamidine, iv spiramycin and vincamine).Increased risk of ventricular arrhythmias and ventricular fibrillation (hypokalemia is a provoking factor). Clinical and ECG monitoring is required.

Propafenone. Violation of contractility, automatism and conduction (inhibition of sympathetic compensatory mechanisms). Clinical and ECG monitoring is required.

Baclofen. Strengthening antihypertensive action. Blood pressure monitoring and dose adjustment of an antihypertensive agent are required.

Insulin and antidiabetic sulfonamides. All β-adrenergic blockers can mask some symptoms of hypoglycemia, such as tachycardia, palpitations (see SPECIAL INSTRUCTIONS). The patient should be warned about the need to strengthen self-monitoring of blood glucose levels.

Cholinesterase inhibitors (ambenomium, donepezil, galantamine, neostigmine, pyridostigmine, rivastigmine, tacrine). The risk of increased bradycardia (additive effect). Regular clinical monitoring is required.

Antihypertensive agents of central action (clonidine, apraclonidine, alpha-methyldopa, guanfancin, moxonidine, rilmenidine). A significant increase in blood pressure with a sharp abolition of the antihypertensive drug of central action. It is necessary to avoid the sudden withdrawal of antihypertensive drugs and conduct clinical monitoring.

Lidocaine (iv). An increase in the concentration of lidocaine in blood plasma with a possible increase in the severity of undesirable neurological and cardiac effects (decreased metabolism of lidocaine in the liver). Clinical and ECG monitoring is recommended, and possibly determining the concentration of lidocaine in blood plasma both during treatment with β-adrenoreceptor blockers and after its termination. If necessary, dose adjustment of lidocaine.

Combinations requiring special attention

NSAIDs (systemic), including selective COX-2 inhibitors. Decreased hypotensive effect (inhibition of vasodilating prostaglandins NSAIDs and fluid and sodium retention by pyrazolone derivatives).

Calcium channel blockers (dihydropyridines). Arterial hypotension, circulatory failure in patients with latent or uncontrolled heart failure. Treatment with β-adrenoreceptor blockers can minimize reflex sympathetic mechanisms that are triggered by excessive hemodynamic reactions.

Antidepressants having an affinity for imipramine, antipsychotics. Strengthening the hypotensive effect and the risk of orthostatic hypotension (additive effect).

Mefloquine. The risk of bradycardia (additive effect on the development of bradycardia).

Dipyridamole (w / w). Strengthening antihypertensive effect.

Blockers of α-adrenergic receptors used in urology (alfuzosin, doxazosin, prazosin, tamsulosin, terazosin). Strengthening antihypertensive effect. Increased risk of orthostatic hypotension.

Amifostine. Strengthening antihypertensive effect.

Cardiac glycosides. A combination that can extend AV conduction time and cause bradycardia.

Fingolimod. The simultaneous use of fingolimod with β-adrenoreceptor blockers can enhance bradycardia, and therefore this combination is not recommended. If simultaneous use is necessary, appropriate monitoring is necessary from the moment of treatment initiation; At a minimum, night monitoring is recommended.

Iodine-containing contrast agents. In case of shock or arterial hypotension due to the introduction of iodine-containing contrast agents, β-adrenoreceptor blockers cause a decrease in cardiovascular compensatory reactions.

If possible, treatment with β-adrenoreceptor blockers should be stopped before radiography. If necessary, the doctor should be able to conduct intensive care.

Corticosteroids and tetracosactides.Decreased antihypertensive effect (water and sodium retention in combination with corticosteroids).

Overdose

Symptoms of an overdose of the drug: bradycardia or a pronounced decrease in hell.

In case of bradycardia or an excessive decrease in blood pressure, it is necessary to administer 1-2 mg of atropine iv, 1 mg of glucagon (repeat the drug if necessary), if necessary, a slow infusion of 25 μg of isoprenaline or 2.5-10 μg / kg / min of dobutamine is administered.

With cardiac decompensation in newborns whose mothers used β-adrenoreceptor blockers during pregnancy: glucagon at the rate of 0.3 mg / kg body weight, hospitalization in the intensive care unit; isoprenaline and dobutamine: usually in fairly high doses and for a long time, under the supervision of a specialist.

Storage conditions

In the original packaging at a temperature not exceeding 25 ° C.