Expiration date: 03/2025

The composition and form of issue: 

Tablets, film-coated, divisible. 1 tablet contains betaxolol hydrochloride 20 mg

excipients: lactose monohydrate — 100 mg of sodium amylopectin glycolate 4 mg MCC — 113 mg silicon dioxide colloidal anhydrous and 1.6 mg of magnesium stearate and 1.4 mg of polymer — 3,90 mg of macrogol 400 and 0.43 mg of titanium dioxide (E171) — 0,67 mg 

14 PCs in blister, in box 2 or 4 blisters.

Description pharmaceutical form:

White biconvex tablets, coated tablets with a dividing line on one side and engraved "KE20" on the other side.

Pharmacokinetics:

Quickly and completely (100%) absorbed from the gastrointestinal tract after oral administration, bioavailability is about 85%. Cmax in plasma achieved through 2-4 h. Betaxolol binds to plasma proteins by approximately 50%.

The permeability of the BBB and placental barrier — low. The secretion of breast milk is insignificant.

The volume of distribution of approximately 6 l/kg betaxolol In the body is mainly transformed into inactive metabolites. Solubility in fats moderate.

Excreted by the kidneys as metabolites (80%), 10-15% in an unmodified form. T1/2 betaxolola — 15-20 h. the elimination half-life in the liver is lengthened by 33%, but clearance does not change if impaired renal function the half-life is doubled (requires dose reduction).

Not removed by hemodialysis.

Description pharmacological action:

Betaxolol is characterised by three pharmacological properties:

• cardioselective beta adrenoblokiruyuschee effect
  
• the lack of partial agonistic activity (i.e. does not show its own sympathomimetic action)
  
• weak membrane stabilizing effect (quinidine-like or local anesthetic) in concentrations exceeding therapeutic.
  

Indications:

• hypertension
  
• prevention of attacks of angina.
  

Contraindications:

• hypersensitivity to betaxolol
  
• severe chronic heart failure IIB–III degree
  
• cardiogenic shock
  
• AV blockade II and III extent (without connection of an artificial pacemaker)
  
• Prinzmetal's angina
  
• syndrome weakness sinusnogo node (including sinoatrial blockade)
  
• bradycardia
  
• hypotension
  
• combination therapy with sultopridom and floktafeninom
  
• simultaneous reception of MAO inhibitors
  
• cardiomegaly (with no signs of heart failure)
  
• the age of 18 years (efficacy and safety not established).
  
• In connection with the presence of lactose, the drug is contraindicated:
  
• in congenital galactosemia
  
• the syndrome of malabsorption of glucose/galactose or lactase deficiency.
  

With caution:

• allergic reactions in anamnesis
  
• pheochromocytoma
  
• metabolic acidosis
  
• obliterating diseases of peripheral vessels ("alternating" claudication, Raynaud's syndrome)
  
• liver failure
  
• chronic renal failure
  
• hemodialysis
  
• myasthenia gravis
  
• depression (including in history)
  
• old age
  
• AV blockade I of a degree
  
• chronic obstructive pulmonary disease (asthma, emphysema)
  
• psoriasis
  
• chronic circulatory insufficiency
  
• thyrotoxicosis
  
• diabetes.
  

Application of pregnancy and breast-feeding:

It was not revealed teratogenic effects of the drug in animal experiments. To date people have not observed teratogenic effects, a controlled prospective study revealed no congenital malformations.

Application of pregnancy is possible only in the case when benefit to the mother outweighs the potential risk to the fetus and/or child.

Beta-blockers penetrate into breast milk (see "Pharmacokinetics"). The risk of hypoglycemia or bradycardia has not been investigated, therefore, at the time of treatment should stop breastfeeding.

Side effects:

From the nervous system: fatigue, weakness, dizziness, headache, drowsiness or insomnia, nightmares, depression, anxiety, confusion or short-term memory loss, hallucinations, asthenic syndrome, muscle weakness, paresthesia in the extremities (in patients with "intermittent" claudication, Raynaud's syndrome), tremor.

From the side of cardiovascular system: sinus bradycardia, palpitations, orthostatic hypotension, conduction disorder of the myocardium, AV blockade (up to heart failure), arrhythmia, weakening of myocardial contractility, the development (or worsening) symptoms of heart failure (swelling of ankles, feet, legs), expressed lower AD, manifestation of angiospasm (decrease peripheral circulation, cold lower extremities, Raynaud's syndrome), chest pain.

From the digestive system: dry mucous membranes of the mouth, nausea, vomiting, abdominal pain, constipation or diarrhea, the human liver (dark urine, yellowness of the sclera or skin, cholestasis), changing taste.

The respiratory system: nasal congestion, difficulty breathing in the appointment of high doses (loss of selectivity) and/or prone patients — laringo - and bronchospasm.

From the sensory organs: visual disturbances, reduced secretion of tear glands, dryness and soreness of eyes, conjunctivitis.

With the skin: increased sweating, hyperemia of skin, exanthema, psoriasiform skin reactions, exacerbation of psoriasis.

Allergic reactions: skin rash, itching, hives.

From the endocrine system: hyperglycemia in patients with insulin-independent diabetes mellitus, hypoglycemia in patients receiving insulin, hypothyroid state.

Effect on fetus: intrauterine growth retardation, hypoglycemia, bradycardia.

Other: pain in the back, artralgia, reduced libido, reduced potency syndrome "cancel" (increasing angina attacks, increased blood pressure).

Laboratory data: in rare cases there is the appearance of antinuclear antibodies, which only in exceptional cases accompanied by clinical manifestations of systemic lupus erythematosus, passing upon cessation of treatment.

Drug interactions:

Many drugs can cause bradycardia. This group includes beta - blockers, antiarrhythmic drugs of class IA (quinidine, disopyramide), amiodarone, and sotalol class III antiarrhythmics, diltiazem and verapamil is class IV, and digitalis glycosides, clonidine, guanfacine, mefloquine, and cholinesterase inhibitors, indicated for the treatment of Alzheimer's disease.

Contraindicated in combination

Floctafenine. In case of shock or hypotension due to floctafenine, beta-blockers cause a reduction in cardiovascular compensatory reactions.

Sultoprid. Bradycardia (additive effect).

Combinations to avoid:

Blockers "slow" calcium channels (bepridil, diltiazem and verapamil). Violations of automatism (expressed aetiology, stopping sinus node), violations AV conduction, heart failure (synergistic effect).

This combination can only be used under careful clinical and electrocardiographic monitoring, especially in elderly patients or early treatment.

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

Combinations that should be used with caution

Halogenated inhalation anesthetics. Beta-blockers reduce the compensatory cardiovascular reactions (during the operation, the effect of blockade of beta-adrenergic receptors can be eliminated beta-agonists). As a rule, therapy of beta-blockers should not be discontinued, and abrupt discontinuation of the drug should be avoided in any case. The anesthesiologist must be informed about the ongoing treatment.

Drugs that can cause atrial fibrillation (except sultopride). Antiarrhythmic drugs class IA (quinidine, hydrogenizing and disopyramide) and class III (amiodarone, dofetilide, ibutilide, sotalol), certain antipsychotics from the group of phenothiazine (chlorpromazine, cyamemazine, levomepromazine, thioridazine), benzamide (amisulpride, sulpiride, tiapride), butyrophenones (droperidol, haloperidol), other neuroleptics (pimozide) and other drugs (cisapride, diphemanil,/erythromycin, halofantrine, mizolastine, moxifloxacin, pentamidine,/in spiramycin and vincamine has).

Increased risk of ventricular arrhythmias, especially the "torsades de pointes" .

Required clinical and electrocardiographic control.

Propafenon. Violations of contractility, automatism and conduction (suppression of sympathetic compensatory mechanisms).

Required clinical and electrocardiographic control.

Baclofen. Increase antihypertensive action.

It is necessary to monitor blood pressure and adjust the dose antihypertensives if necessary.

Insulin and oral sulfonylureas. All beta - blockers may mask certain symptoms of hypoglycaemia: palpitations and tachycardia.

The patient should be warned of the need to strengthen self-monitor blood sugar levels, especially at the beginning of treatment.

Cholinesterase inhibitors (ambenonium, donepezil, galantamine, neostigmine, pyridostigmine, rivastigmine, tacrine). The risk of increasing bradycardia (additive effect).

Requires regular clinical monitoring.

Antihypertensives Central action (clonidine, alpha - methyldopa, guanfacin, moxonidine, rilmenidine). Significant increase in blood pressure in the abrupt cancellation of antihypertensive drugs of Central action.

It is necessary to avoid abrupt withdrawal antihypertensive agents and to conduct clinical supervision.

Lidocaine. the Increase in the concentration of lidocaine in plasma with a possible undesirable increase in neurological symptoms and effects of the cardiovascular system (decrease the metabolism of lidocaine in the liver).

Recommended clinical and electrocardiographic monitoring and possibly control the concentration of lidocaine in blood plasma during treatment with beta-blockers and after its termination. If necessary, correction doses of lidocaine.

Combinations to be taken into account

NSAIDs (systemic), including selective COX-2 inhibitors. Reduced antihypertensive effect (inhibition of synthesis of PG and water retention and sodium pirazolonovykh derivatives).

BPC. Hypotension, circulatory failure in patients with latent or uncontrolled cardiac insufficiency. Treatment beta-blockers can minimize reflex sympathetic mechanisms.

Tricyclic antidepressants (such as imipramine), antipsychotics. The antihypertensive effect and risk of orthostatic hypotension (additive effect).

Mefloquine. The risk of bradycardia (additive effect).

Dipyridamole (in/in). Increase antihypertensive effect.

Alpha-blockers used in urology (alfuzosin, doxazosin, prazosin, tamsulosin, terazosin). Increase antihypertensive effect. Increased risk of orthostatic hypotension.

Amifostine. Increase antihypertensive effect.

Allergens, used for immunotherapy or allergen extracts for skin tests, increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving betaxolol.

Phenytoin in the on/in the introduction increases the severity cardiodepressive actions and reduce the likelihood of AD.

Decreases the clearance xantinov (except difillina) and increases their concentration in plasma, especially in patients with initially increased clearance of theophylline (for example under the influence of Smoking).

Hypotensive effect weaken estrogens (delay sodium).

Cardiac glycosides, methyldopa, reserpine, and guanfacine increase the risk of developing or exacerbating bradycardia, AV block, cardiac arrest.

Nifedipine can lead to significant reduction of AD.

Diuretics, clonidine, sympatholytic, hydralazine, and other antihypertensive drugs can lead to excessive reduction of AD.

Prolongs the action of non-depolarizing muscle relaxants and anticoagulant effect of coumarins.

Ethanol, sedatives and hypnotics drugs increase oppression CNS.

Not recommended simultaneous application with MAO inhibitors because of significant increase gipotenzivnogo actions, break in treatment between receiving MAO inhibitors and betaxolol shall be not less than 14 days.

Non-hydrogenated ergot alkaloids increase the risk of peripheral circulatory disorders.

Method of application and dose:

Inside, not liquid, squeezed enough liquid.

Initial dose 1 table. (20 mg) per day.

Dosage in patients with renal insufficiency

The dose must be installed in accordance with renal function of the patient: dosage is not required when Cl creatinine >20 ml/min. However, early treatment is recommended clinical observation before reaching the equilibrium levels of the drug in the blood (average 4 days).

In patients with severe renal insufficiency (Cl creatinine <20 ml/min) the recommended initial dose of 5 mg/day (in patients on hemodialysis — regardless of the frequency and duration of sessions of hemodialysis).

Dosage in patients with hepatic insufficiency

In patients with hepatic impairment a dosage adjustment is not usually required. However, at the beginning of therapy, it is recommended that more careful clinical monitoring of the patient.

Overdose:

Symptoms: bradycardia, dizziness, AV blockade, expressed lower AD, arrhythmia, ventricular extrasystole, fainting, heart failure, difficulty breathing, bronchospasm, cyanosis of the finger nails and palms, seizures.

Treatment: gastric lavage, purpose of absorbent material

in the case of bradycardia or excessive blood pressure reduction should apply the following measures:

atropine 1-2 mg in/in

1 mg of glucagon (possibly again), accompanied, if necessary, slow infusion of 25 µg of isoprenaline or introduction dobutamine of 2.5–10 mcg/kg/min In the case of cardiac decompensation in neonates whose mothers during pregnancy took beta-blockers: glucagon at the rate of 0.3 mg/kg hospitalization in the ICU isoprenaline and dobutamine, usually in fairly high doses and long-term, which require monitoring specialist.

Special instructions:

Treatment of patients with angina should never interrupt abruptly — cancels can lead to serious cardiac arrhythmias, myocardial infarction, or sudden death.

Lactose

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

It is essential to monitor patients receiving Lokren® , which should include the monitoring of HR and AD (at the beginning of treatment daily, then 1 every 3 -4 months), the content of glucose in patients with diabetes mellitus (1 once in 4-5 mo) requires monitoring of renal function in elderly patients (1 every 4-5 months).

Should teach the patient methods of calculating heart rate and instruct on the need of medical advice in heart rate <50 beats/min.

Treatment should not be discontinued abruptly, particularly in patients with coronary artery disease. The dose should be reduced gradually, i.e. over 1-2 weeks, and if necessary, you can start replacement therapy to avoid the progression of angina.

About 20% of patients with angina, beta-blockers are not effective.

The main reason — severe coronary atherosclerosis with the low threshold of ischemia (heart rate at the time of the development of anginal attack <100 beats/min) and increased end - diastolic pressure of the left ventricle that violate the upper subendocardialnah blood flow.

At the same time taking clonidine its reception can be terminated only a few days after the cancellation Lorena.

Lokren should be lifted before the examination of blood and urine catecholamines, normetanephrine and vanillylmandelic acid, titles of antinuclear antibodies.

Bronchial asthma and chronic obstructive pulmonary disease

Beta-blockers may be administered to patients only with moderate degree of severity of the disease, with the selection of a selective beta-adrenoreceptor in the lower initial dose. Before beginning treatment it is recommended to assess respiratory function.

With the development of seizures during treatment can be used bronchodilators — &beta2-agonists.

Heart failure

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

Bradycardia

The dose should be reduced if heart rate at rest below 50-55 beats/min and patient has clinical manifestations of bradycardia.

AV blockade I of a degree

Given the negative Chrono dromotroponoe effect of beta-blockers, with the blockade of I degree, the drug should be used with caution.

Prinzmetal's Angina

Beta-blockers may increase the number and duration of attacks in patients with angina prinzmetals. The use of cardioselective beta1 - blockers is possible with less heavy and mixed forms, provided that the treatment is carried out in combination with vasodilators.

Peripheral circulatory disorders

Beta-blockers can worsen the condition of patients suffering from peripheral circulatory disorders (Raynaud's disease or Raynaud's syndrome, arteritis or chronic obliterating diseases of lower limb arteries).

Pheochromocytoma

In the case of the use of beta-blockers in the treatment of hypertension caused by pheochromocytoma, requires careful control of AD.

Elderly patients

Treatment of elderly patients should start with small doses and under strict surveillance.

Patients with renal insufficiency

The dose should be adjusted depending on the concentration of creatinine in blood or creatinine clearance (see "Method of application and dosage").

Patients with diabetes

You should warn the patient about the need to strengthen self-monitoring of glucose levels in the blood at the beginning of treatment. The initial symptoms of hypoglycaemia may be masked, particularly tachycardia, palpitations and sweating.

Psoriasis

Requires careful evaluation of the necessity of prescribing, because there are reports of deterioration during treatment with beta-blockers.

Allergic reactions

Patients prone to severe anaphylactic reactions, particularly involving the use floctafenine or while conducting desensitization therapy beta - blockers can lead to a further strengthening of the reactions and decrease the effectiveness of treatment.

General anesthesia

Beta-blockers mask the reflex tachycardia and increase the risk of hypotension. Continuation of therapy with beta-blockers reduces the risk of arrhythmia, myocardial ischemia, and hypertensive crises. The anesthesiologist should communicate that the patient is receiving treatment with beta-blockers.

If discontinuation of treatment is considered necessary, it should be noted that the termination of therapy at 48 hours allows you to restore responsiveness to catecholamines.

Therapy 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 interruption of beta-blockers

in the case of emergency or in cases where termination of treatment is not possible, the patient should be protected from the effects of the excitation of the vagus nerve by an appropriate premedication with atropine, with repetition if necessary. For General anesthesia it is necessary to use substances the least depressing the myocardium.

Account should be taken of the risk of anaphylactic reactions.

Thyrotoxicosis

Symptoms of thyrotoxicosis may be masked for the therapy of beta - blockers.

Athletes

Athletes should be aware that the drug contains active substance, which can give a positive reaction in tests of doping control.

At the time of treatment to eliminate the use of ethanol.

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

The "smokers" the effectiveness of beta-adrenoblokatorov below.

Newborns whose mothers were treated with beta-blockers, the effect persists for several days after birth. Although this residual effect may not have clinical consequences, however, may develop heart disease that requires intensive care of the newborn (see "Overdose"). In this situation, you should avoid putting increases blood volume solutions (risk of acute pulmonary edema). There are also reports of bradycardia, respiratory distress syndrome and hypoglycemia. It is therefore recommended that careful monitoring of newborns in specialized conditions (control heart rate and glucose level in the blood during the first 3-5 days of life).