Lokren, 20 mg, film-coated tablets, 56 pcs., Sanofi-Aventis France buy in Moscow at a low price

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.

Lokren®

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

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 beta 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, beta-blockers reduce compensatory cardiovascular reactions. If possible, treatment with a beta-blocker should be discontinued before radiographic examinations using iodinated contrast media. If it is necessary to continue therapy with a beta-blocker, the doctor must provide appropriate conditions for intensive therapy.

With inhaled halogenated anesthetics

Beta-blockers reduce compensatory cardiovascular responses (inhibition of beta-adrenergic receptors can be reduced by the administration of beta-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 beta-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, procaine amide);

- 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, sulypopride, sulpiride, tiapride), butyrophenones (droperidol, haloperidol);
other antipsychotics (pimozide, sertindole);
antidepressants: tricyclic antidepressants, selective serotonin reuptake inhibitors (citalopram, escitalopram);
antibacterial agents: fluoroquinolones (levofloxacin, moxifloscacin, sparfloxacin, ciprofloxacin), macrolides (erythromycin for intravenous administration, spiramycin for intravenous administration, azithromycin, clarithromycin, roxithromycin), co-trimoxazole;
antifungals: azoles (voriconazole, ytraconazole, 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 the motility of the gastrointestinal tract (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 beta 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, alpha-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 beta-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 alpha-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 beta blockers.

With drugs that induce sinus arrest

Sinus node arrest is possible with simultaneous use of beta-blockers, including Lokren®, with drugs that can cause sinus node arrest.

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.

Lokren

Monitoring of patients taking tablets should include monitoring heart rate and blood pressure (at the beginning of treatment - daily, then once every 3-4 months), blood glucose levels in patients with diabetes mellitus (once every 4-5 months). In elderly patients, it is recommended to monitor renal function (once every 4-5 months).

The patient should be taught how to calculate heart rate and instructed about the need for medical consultation if the heart rate is less than 50/min.

In approximately 20% of patients with angina, beta blockers are ineffective. The main reasons are severe coronary atherosclerosis with a low ischemic threshold (heart rate at the time of development of an anginal attack less than 100/min) and increased LV end-diastolic pressure, disrupting subendocardial blood flow. In smokers, the effectiveness of beta-blockers is lower.

Patients using contact lenses should take into account that during treatment the production of tear fluid may decrease.

In thyrotoxicosis, betaxolol may mask certain clinical signs of thyrotoxicosis (for example, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated because it can increase symptoms. In diabetes mellitus, it can mask tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, it practically does not enhance insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentrations to normal levels.

When taking clonidine concomitantly, it can be discontinued only a few days after stopping betaxolol.

It is possible that the severity of the hypersensitivity reaction may increase and the absence of effect from usual doses of epinephrine against the background of a burdened allergic history.

A few days before general anesthesia with chloroform or ether, you must stop taking the drug. If the patient took the drug before surgery, he should select a drug for general anesthesia with minimal negative inotropic effect.

Reciprocal activation of the n.vagus can be eliminated by intravenous administration of atropine (1-2 mg).

Drugs that reduce catecholamine reserves (for example, reserpine) can enhance the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision to detect arterial hypotension or bradycardia.

Patients with bronchospastic diseases can be prescribed cardioselective adrenergic blockers in case of intolerance and/or ineffectiveness of other antihypertensive drugs, but the dosage should be strictly monitored. An overdose is dangerous due to the development of bronchospasm.

If elderly patients develop increasing bradycardia (less than 50/min), arterial hypotension (systolic blood pressure below 100 mm Hg), AV block, bronchospasm, ventricular arrhythmias, severe liver and kidney dysfunction, it is necessary to reduce the dose or stop treatment . It is recommended to discontinue therapy if depression caused by taking beta-blockers develops.

Treatment should not be abruptly interrupted due to the risk of developing severe arrhythmias and myocardial infarction. Cancellation is carried out gradually, reducing the dose over 2 weeks or more (reduce the dose by 25% in 3-4 days).

Use during pregnancy and lactation is possible if the benefit to the mother outweighs the risk of side effects in the fetus and child.

Should be discontinued before testing the content of catecholamines, normetanephrine and vanillylmandelic acid in the blood and urine; antinuclear antibody titers.

During the period of treatment with the drug, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

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.

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.

Lokren, 56 pcs., 20 mg, film-coated tablets

Treatment for patients with angina should never be interrupted abruptly - withdrawal can lead to severe heart rhythm disturbances, myocardial infarction or sudden death.

Lactose

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

It is necessary to monitor patients taking Lokren®, which should include monitoring heart rate and blood pressure (daily at the beginning of treatment, then once every 3–4 months), glucose levels in patients with diabetes mellitus (once every 4–5 months); Monitoring of kidney function is necessary in elderly patients (once every 4–5 months).

The patient should be taught how to calculate heart rate and instructed about the need for medical consultation if heart rate is <50 beats/min.

Treatment should not be stopped abruptly, especially in patients with coronary artery disease. The dose should be reduced gradually, i.e. for 1–2 weeks, and if necessary, replacement therapy can be started at the same time to avoid progression of angina.

In approximately 20% of patients with angina, beta blockers are not effective.

The main reasons are severe coronary atherosclerosis with a low ischemic threshold (heart rate at the time of development of an anginal attack <100 beats/min) and increased end-diastolic pressure of the left ventricle, disrupting subendocardial blood flow.

When taking clonidine simultaneously, it can be discontinued only a few days after stopping Lokren®.

Lokren® should be discontinued before testing the levels of catecholamines, normetanephrine and vanillylmandelic acid in the blood and urine; antinuclear antibody titers.

Bronchial asthma and chronic obstructive pulmonary disease

Beta blockers can be prescribed to patients with only moderate severity of the disease, with the choice of a selective beta blocker at a low initial dose. Before starting treatment, it is recommended to assess respiratory function.

If attacks develop during treatment, bronchodilators - β2-adrenergic agonists can be used.

Heart failure

In patients with heart failure controlled therapeutically, if necessary, betaxolol can be used in very low, gradually increasing doses under strict medical supervision.

Bradycardia

The dose should be reduced if the resting heart rate is below 50–55 beats/min and the patient has clinical manifestations of bradycardia.

AV block 1st degree

Considering the negative dromotropic effect of beta-blockers, the drug should be used with caution during first-degree blockade.

Prinzmetal's angina

Beta blockers may increase the number and duration of attacks in patients suffering from Prinzmetal's angina. The use of cardioselective beta1-blockers is possible for less severe and mixed forms, provided that treatment is carried out in combination with vasodilators.

Peripheral circulation disorders

Beta-blockers can lead to a deterioration in the condition of patients suffering from peripheral circulatory disorders (Raynaud's disease or Raynaud's syndrome, arteritis or chronic occlusive diseases of the arteries of the lower extremities).

Pheochromocytoma

When beta-blockers are used in the treatment of arterial hypertension caused by pheochromocytoma, careful monitoring of blood pressure is required.

Elderly patients

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

Patients with kidney failure

The dose must be adjusted depending on the concentration of creatinine in the blood or creatinine clearance (see "Dosage and Administration").

Patients with diabetes

The patient should be warned about the need to strengthen self-monitoring of blood glucose levels at the beginning of treatment. Initial symptoms of hypoglycemia may be masked, especially tachycardia, palpitations and sweating.

Psoriasis

A careful assessment of the need to prescribe the drug is required, because There are reports of worsening of the condition during treatment with beta-blockers.

Allergic reactions

In patients prone to severe anaphylactic reactions, especially those associated with the use of floctafenine or during desensitization, therapy with beta-blockers may lead to a further increase in reactions and a decrease in the effectiveness of treatment.

General anesthesia

Beta-blockers mask reflex tachycardia and increase the risk of developing arterial hypotension. Continuing therapy with beta-blockers reduces the risk of arrhythmia, myocardial ischemia and hypertensive crises. The anesthesiologist should be informed that the patient has been treated with beta-blockers.

If discontinuation of treatment is considered necessary, it should be taken into account that stopping therapy for 48 hours allows for the restoration of sensitivity to catecholamines.

Therapy with beta-blockers should not be interrupted in the following cases:

in patients with coronary insufficiency, it is advisable to continue treatment until surgery, given the risk associated with sudden withdrawal of beta-blockers;

In case of emergency operations or in cases where cessation of treatment is not possible, the patient should be protected from the effects of vagus nerve stimulation by appropriate premedication with atropine, repeated if necessary. For general anesthesia, it is necessary to use substances that depress the myocardium to the least extent.

The risk of developing anaphylactic reactions must be taken into account.

Thyrotoxicosis

Symptoms of thyrotoxicosis may be masked by 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.

Avoid drinking ethanol during treatment.

Patients who use contact lenses should take into account that during treatment, tear fluid may decrease.

In smokers, the effectiveness of beta-blockers is lower.

In newborns whose mothers were treated with beta-blockers, the effect of the latter persists for several days after birth. Although this residual effect may not have clinical consequences, it is nevertheless possible to develop heart defects requiring intensive care in the newborn (see “Overdose”). In such a situation, administration of solutions that increase blood volume should be avoided (risk of developing acute pulmonary edema). There have also been reports of bradycardia, respiratory distress syndrome and hypoglycemia. Therefore, careful monitoring of newborns in specialized conditions is recommended (monitoring heart rate and blood glucose levels during the first 3–5 days of life).

Interactions of the drug Lokren

Many drugs can cause bradycardia: β-adrenergic receptor blockers, class Ia antiarrhythmic drugs (quinidine, disopyramide), class III (amiodarone, sotalol), class IV (diltiazem, verapamil), cardiac glycosides, clonidine, guafancin, mefloquine, cholinesterase inhibitors (used for the treatment of Alzheimer's disease). The simultaneous use of Lokren with the following drugs is contraindicated:

floctafenine: in case of shock or arterial hypotension caused by taking floctafenine, β-adrenergic receptor blockers cause a decrease in the severity of compensatory reactions of the cardiovascular system;
sultopride: disturbances in cardiac automaticity (severe bradycardia) caused by the additive effect of drugs.

The use of Lokren with the following drugs is not recommended:

calcium channel blockers (bepridil, diltiazem, verapamil and mebefradil): possible violations of automaticity (excessive bradycardia, dysfunction of the sinus node), impaired AV conduction, heart failure (synergistic effect).
amiodarone: negative inotropic effect, disturbances of automaticity and conduction (suppression of sympathetic compensatory mechanisms).

Caution is required when using Lokren with the following drugs:

inhaled halogenated anesthetics: β-adrenergic receptor blockers suppress compensatory reactions of the cardiovascular system (during surgery, β-adrenergic receptor blockade can be eliminated by the use of β-adrenergic agonists). In general, β-adrenergic blocker therapy should not be discontinued, much less abruptly, in any case; it is necessary to inform the anesthesiologist about the treatment being carried out.
drugs that can provoke atrial fibrillation (except sultopride): class Ia (quinidine, hydroquinidine and disopyramide) and class III antiarrhythmic drugs (amiodarone, dofetilide, ibutilide, sotatol); some phenothiazine group neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine), benzamides (amisulpride, sulpiride, tiapride), butyrophenones (droperidol, haloperidol), other antipsychotics (pimozide) and other drugs (cisapride, difemanil, erythromycin for intravenous administration, halofantrine, mizolastine, moxifloxacin, pentamidine, vincamine and spiramycin for intravenous administration) - increased risk of developing ventricular arrhythmia and ventricular fibrillation (hypokalemia is a provoking factor); clinical and electrocardiographic monitoring is required;
propafenone: disturbance of cardiac contractility, automaticity and conduction (suppression of sympathetic compensatory mechanisms), which requires clinical and electrocardiographic monitoring;
baclofen: potentiation of the antihypertensive effect, monitoring of blood pressure levels and dose adjustment of the antihypertensive drug is necessary if necessary;
insulin and oral hypoglycemic agents of the sulfonamide group: beta-adrenergic blockers may mask some symptoms of hypoglycemia (tachycardia, palpitations, sweating), so the patient should be warned about the need to strictly monitor blood glucose levels;
cholinesterase inhibitors (ambenonium, donepezil, galantamine, neostigmine, pyridostigmine, rivastigmine, tacrine): risk of increased bradycardia (additive effect); regular clinical monitoring is required;
centrally acting antihypertensive drugs (clonidine, apraclonidine, alpha-methyldopa, guanfancin, moxonidine, rilmenidine): a significant increase in blood pressure with abrupt withdrawal of the centrally acting antihypertensive drug; sudden withdrawal of antihypertensive drugs should be avoided and clinical monitoring should be carried out;
lidocaine (iv): it is possible to reduce metabolism in the liver and increase its concentration in the blood plasma with the development of side effects from the nervous and cardiovascular systems.

Lidocaine dose adjustment is necessary; clinical observation and ECG monitoring are recommended, monitoring the concentration of lidocaine in the blood plasma:

NSAIDs, including selective COX-2 inhibitors: decreased hypotensive effect (inhibit the synthesis of prostaglandins that have a depressant effect; retention of sodium and water ions in the body when using pyrazolone derivatives);
dihydropyridine calcium channel blockers: arterial hypotension, development of symptoms of heart failure in patients with latent or uncontrolled heart failure. Treatment with β-adrenergic receptor blockers minimizes reflex sympathomimetic mechanisms triggered by excessive hemodynamic reactions;
iodinated contrast agents: in the case of anaphylactic reactions and arterial hypotension caused by iodinated contrast agents, β-adrenergic receptor blockers reduce the severity of compensatory reactions of the cardiovascular system.

If possible, treatment with beta-adrenergic blockers should be suspended until radiological examination is carried out. If it is necessary to continue treatment, it is necessary to prepare in advance the appropriate means for resuscitation measures:

tricyclic antidepressants, antipsychotics: increased hypotensive effect and risk of developing orthostatic hypotension (additive effect);
mefloquine: risk of bradycardia (additive effect);
dipyridamole (iv): enhanced antihypertensive effect;
α-adrenergic receptor blockers (alfuzosin, doxazosin, prazosin, tamsulosin, terazosin): increased antihypertensive effect, increased risk of orthostatic hypotension;
amifostine: enhanced antihypertensive effect.

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.

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.

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.