Instructions for use LOKREN
Combinations are contraindicated
With the development of shock or arterial hypotension caused by floctafenine, concomitantly used beta-blockers cause a decrease in compensatory cardiovascular reactions.
When used simultaneously with sultopride, excessive bradycardia may develop due to the additive effect of reducing heart rate.
When used simultaneously with MAO inhibitors, a significant increase in the hypotensive effect is observed. The interval between the end of treatment with MAO inhibitors and the start of taking betaxolol should be at least 14 days.
Combinations are not recommended
When used simultaneously with amiodarone, disturbances in contractility, automaticity and conduction are possible (suppression of sympathetic compensatory mechanisms).
When used simultaneously with calcium channel blockers (bepridil, diltiazem, verapamil), automatism disturbances (severe bradycardia, sinus node blockade), AV conduction disturbances, and heart failure (due to synergism) are possible. Combination therapy is possible only in exceptional cases under careful clinical and ECG control, especially in elderly patients or at the beginning of treatment.
Combinations to use with caution
When prescribing inhaled halogen-containing anesthetics, beta-blockers cause a decrease in compensatory reactions from the cardiovascular system (during surgery, suppression of beta-adrenergic receptors can be eliminated by beta-agonists). In general, beta-blocker therapy should not be discontinued, and abrupt discontinuation of the drug should be avoided in any case. The anesthesiologist should be informed of the treatment being carried out.
With simultaneous use of Lokren with antiarrhythmic drugs of class IA (quinidine, hydroquinidine and disopyramide) and class III (amiodarone, dofetilide, ibutilide, sotalol), antipsychotics from the phenothiazine group (chlorpromazine, cyamemazine, levomepromazine, thioridazine), benzamide (amisulpride, sulpiride, tiapride ), butyrophenones (droperidol, haloperidol), other antipsychotics (pimozide) and other drugs (cisapride, difemanil, erythromycin IV, halofantrine, mizolastine, moxifloxacin, pentamidine, spiramycin IV and vincamine IV) increase the risk of developing ventricular arrhythmia , especially the “pirouette” type. If combination therapy is necessary, clinical and ECG monitoring is required.
When used simultaneously with propafenone, disturbances in contractility, automaticity and conduction are possible due to suppression of sympathetic compensatory mechanisms. If combination therapy is necessary, clinical and ECG monitoring is required.
When used simultaneously with baclofen, the antihypertensive effect is enhanced. This combination requires blood pressure monitoring and, if necessary, dose adjustment of antihypertensive drugs.
When used simultaneously with insulin and oral sulfonylurea hypoglycemic agents, it should be borne in mind that beta-blockers may mask some symptoms of hypoglycemia. The patient should be warned about the need to strengthen self-monitoring of blood glucose levels.
When used simultaneously with cholinesterase inhibitors (ambenonium, donepezil, galantamine, neostigmine, pyridostigmine, rivastigmine, tacrine), there is a risk of increased bradycardia (additive effect). These combinations require regular clinical monitoring.
In the case of combination therapy with centrally acting antihypertensive drugs (clonidine, apraclonidine, alpha-methyldopa, guanfacine, moxonidine, rilmendine), a significant increase in blood pressure occurs when they are discontinued. Abrupt withdrawal of antihypertensive drugs should be avoided and clinical monitoring should be ensured.
When used concomitantly with intravenous lidocaine, it is possible to increase the concentration of lidocaine in the blood plasma with a possible increase in undesirable neurological effects and symptoms from the cardiovascular system (due to a decrease in the metabolism of lidocaine in the liver). Clinical observation, ECG monitoring and, possibly, monitoring of lidocaine plasma concentrations are recommended during combination therapy and after its cessation; if necessary, adjust the dose of lidocaine.
Combinations to Consider
When used simultaneously with NSAIDs, the hypotensive effect of the drug may be reduced (NSAIDs inhibit the synthesis of vasodilating prostaglandins, pyrazolone derivatives cause water and sodium retention).
When used simultaneously with calcium channel blockers, arterial hypotension and decompensation may occur in patients with latent or uncontrolled heart failure. Treatment with beta-blockers may minimize reflex sympathetic mechanisms.
With simultaneous use of tricyclic antidepressants (such as imipramine), antipsychotics can enhance the hypotensive effect and increase the risk of developing orthostatic hypotension (additive effect).
With simultaneous use of GCS and tetracosactide, they reduce the hypotensive effect (due to water and sodium retention).
When used concomitantly, mefloquine increases the risk of bradycardia (additive effect on the development of bradycardia).
Dipyridamole (iv), amifostine enhance the antihypertensive effect of Lokren.
Alpha-blockers used in urology (alfuzosin, doxazosin, prazosin, tamsulosin, terazosin) enhance the antihypertensive effect of betaxolol, thereby increasing the risk of orthostatic hypotension.
Allergens used for immunotherapy or allergen extracts for skin testing increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving betaxolol.
Phenytoin (iv) increases the severity of the cardiodepressive effect and the likelihood of lowering blood pressure in patients receiving betaxolol.
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).
The hypotensive effect of betaxolol is reduced under the influence of estrogens (due to sodium retention).
Cardiac glycosides, methyldopa, reserpine and guanfacine increase the risk of developing or worsening bradycardia, AV block, and cardiac arrest.
Nifedipine may lead to a significant decrease in blood pressure in patients receiving betaxolol.
Diuretics, clonidine, sympatholytics, hydralazine and other antihypertensive drugs can lead to an excessive decrease in blood pressure.
Betaxolol increases the duration of action of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins.
When used simultaneously with sedatives and hypnotics, with ethanol, the inhibitory effect on the central nervous system increases.
Non-hydrogenated ergot alkaloids increase the risk of developing peripheral circulatory disorders in patients receiving betaxolol.
Pharmacological properties of the drug Lokren
Pharmacodynamics . Betaxolol (( RS )-l-[4-[2-(cyclopropylmethoxy)ethyl]phenoxy]-3-[(1-methylethyl)amino]-2-propan-2-ol) is characterized by three pharmacological properties: β1-adrenergic blocking ( cardioselective) effect, lack of partial agonist activity (PCA) and weakly expressed membrane-stabilizing effect (similar to that of quinidine or local anesthetics) in doses exceeding therapeutic ones. Pharmacokinetics. Absorption. Quickly and completely absorbed after oral administration. The effect of the first pass through the liver is insignificant, bioavailability is about 85%, which ensures minor differences in its concentration in the blood plasma in different patients or in the same patient with prolonged use of the drug. Approximately 50% of betaxolol binds to plasma proteins. Metabolism. 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. Excretion. T1/2 is 15–20 hours.
Overdose of the drug Lokren, symptoms and treatment
Symptoms: bradycardia, marked decrease in blood pressure. Treatment: for bradycardia or severe arterial hypotension, 1–2 mg of atropine is administered intravenously, 1 mg of glucagon (the drug is repeated if necessary); if necessary, slow intravenous infusion of 25 mcg of isoprenaline or administration of dobutamine at a rate of 2.5–10 mcg/kg/min. For cardiac decompensation in newborns whose mothers took β-adrenergic receptor blockers during pregnancy: glucagon at a rate of 0.3 mg/kg; admission to the intensive care unit; isoprenaline and dobutamine, usually in fairly high doses and for a long time, under the supervision of a resuscitator.
Side effects of the drug Lokren
Asthenia, cold extremities, bradycardia (sometimes severe), abdominal pain, nausea, vomiting, impotence, dizziness, headache, insomnia, rarely - slowing of AV conduction or progression of AV blockade, heart failure, arterial hypotension, bronchospasm, hypoglycemia, Raynaud's syndrome, increased intermittent claudication, skin reactions, including psoriasis-like rashes or exacerbation of psoriasis, paresthesia, dry eyes, nightmares. In rare cases, the appearance of a titer of antinuclear antibodies is noted, which only in exceptional cases is accompanied by clinical manifestations such as systemic lupus erythematosus, which disappear after discontinuation of the drug.
Special instructions for the use of the drug Lokren
Discontinuation of the drug. Treatment should not be stopped abruptly, especially in patients with coronary artery disease. The dose of the drug should be reduced gradually over 1–2 weeks, while starting therapy with another drug. BA and COPD . β1-adrenergic receptor blockers for COPD can only be prescribed 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. Heart failure . For patients with compensated heart failure, Lokren is prescribed at a low initial dose. In the future, if necessary, it is gradually increased under strict medical supervision. Bradycardia . The dose of the drug must be reduced if the resting heart rate is below 50–55 beats/min. 1st degree AV block . Considering the negative dromotropic effect of β2-adrenergic receptor blockers, Lokren is used with caution in patients with first-degree AV blockade. Prinzmetal's angina . When using β-adrenergic receptor blockers, the number and duration of angina attacks may increase. The use of the drug is possible with moderate severity and subject to the simultaneous administration of vasodilators. Peripheral circulation disorders . 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). Pheochromocytoma . 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. Elderly patients . Caution should be exercised when prescribing the drug to elderly patients; Treatment begins with the use of the drug in low doses under strict medical supervision. Kidney failure . In patients with renal failure, the dose of the drug must be adjusted depending on the level of creatinine in the blood plasma or creatinine clearance. Diabetes . Patients with diabetes mellitus should be warned about the need to strictly monitor serum glucose levels at the beginning of treatment, since the drug may mask the symptoms of hypoglycemia (tachycardia, palpitations, sweating). Psoriasis. The drug is prescribed with caution to patients with psoriasis, as there are reports of exacerbation of the disease during treatment with β-adrenergic receptor blockers. Allergic reactions . 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. General anesthesia . During anesthesia, β-adrenergic receptor blockers suppress reflex tachycardia and increase the risk of developing arterial hypotension. Continued treatment with beta-adrenergic blockers reduces the risk of arrhythmia, myocardial ischemia and hypertensive crisis. The anesthesiologist should be informed that the patient is taking a β-adrenergic blocker. If anesthesia is necessary, it is considered sufficient to discontinue the drug 48 hours before surgery 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. Thyrotoxicosis . β-adrenergic receptor blockers mask the cardiac symptoms of thyrotoxicosis. Athletes . The drug may give a positive reaction during doping control tests. During pregnancy and breastfeeding . Lokren 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. Children . The safety and effectiveness of the drug in children have not been established, therefore Lokren should not be used in pediatric practice. There is no data on the effect on reaction speed when driving vehicles and working with machinery.
Use of the drug Lokren
Usually prescribed at a dose of 20 mg 1 time per day. The maximum recommended dose is 40 mg/day. In patients with renal failure, the clearance of betaxolol decreases with deterioration of renal function. The dose should be adapted to the state of renal function; with creatinine clearance ≥20 ml/min, no dose adjustment is required. However, at the beginning of treatment, it is recommended to conduct clinical observation until equilibrium drug levels in the blood are achieved (on average 4 days). For patients with severe renal failure (creatinine clearance - 20 ml/min) and patients undergoing dialysis, an initial dose of 10 mg / day is recommended (regardless of the frequency and schedule of dialysis procedures). There is no need for dose adjustment in patients with liver failure, however, clinical observation is advisable at the beginning of therapy.
Contraindications to the use of the drug Lokren
History of anaphylactic reactions, hypersensitivity to betaxolol or other components of the drug, asthma and severe forms of COPD, decompensated refractory heart failure, cardiogenic shock, II-III degree AV block in patients without an implanted pacemaker, Prinzmetal's angina, sick sinus syndrome ( including sinoatrial block), bradycardia (less than 45–50 beats/min), severe forms of Raynaud's syndrome and peripheral circulatory disorders, untreated pheochromocytoma, severe arterial hypotension, concomitant therapy with floctafenine, sultopride, amiodarone, bepridil, diltiazem and verapamil (see INTERACTIONS ), congenital galactosemia, glucose/galactose malabsorption syndrome or lactase deficiency (the drug contains lactose), breastfeeding period, age up to 14 years.
