Lokren, 20 mg 28 pcs.

Locren is a selective beta 1 -adrenoblocker without intrinsic sympathomimetic activity.

In high doses (at concentrations higher than therapeutic) it has a weak membrane stabilizing effect.

Indications

– Arterial hypertension
– Prevention of angina attacks.

Active ingredient

Composition

1 film-coated tablet contains:

Betaxolol hydrochloride 20 mg,

Associated substances:

lactose monohydrate,

amylopectin sodium glycolate,

microcrystalline cellulose,

colloidal anhydrous silicon dioxide,

magnesium stearate,

/p>

Hypromellose,

MacroGol 400,

Titanium dioxide (E171).

How to take, the dosage

The average therapeutic dose is 20 mg (1 tablet) once daily.

When discontinuing treatment, it is recommended that the dose be gradually reduced over 1-2 weeks, especially in patients with CHD, to prevent the development of withdrawal syndrome (due to secondary activation of the sympathetic nervous system).

The tablets are taken orally without chewing and with plenty of fluid.

In patients with impaired renal function and creatinine clearance (CK) of 20 ml/min or more, as well as in patients with hepatic impairment, no adjustment of the daily dose of Lockren is required. However, at the beginning of treatment it is recommended to conduct clinical observation until equilibrium concentrations of the drug in plasma are reached (on average – 4 days).

For patients with severe renal insufficiency (CKR less than 20 ml/min) and those on hemodialysis, the recommended starting dose of Lokren is 5 mg/day, regardless of the frequency and timing of hemodialysis sessions.

Interaction

Many medications can cause bradycardia. This group includes beta-adrenoblockers, class IA antiarrhythmic drugs (quinidine, disopyramide), amiodarone and sotalol from class III antiarrhythmic drugs, diltiazem and verapamil from class IV, and foxglove glycosides, clonidine, guanfacine, mefloquine and cholinesterase inhibitors indicated for Alzheimer’s disease treatment.

Contraindicated combinations
When used concomitantly with floktafenin (in case of development of shock or arterial hypotension due to floktafenin) beta-adrenoblockers may lead to decreased compensatory responses from the cardiovascular system. Simultaneous use with sultopride results in marked bradycardia (additive effect).

Combinations to be avoided Concomitant use with calcium channel blockers (bepridil, diltiazem and verapamil) causes automatism disorders (marked bradycardia, sinus node arrest), AV conduction disorders, heart failure (synergism). This combination should be used only under close clinical observation and ECG monitoring (especially in elderly persons or at the beginning of therapy). Concomitant use with amiodarone may cause contractility, automaticity and conduction disorders (inhibition of sympathetic compensatory mechanisms).

Combinations to be used with caution
When using halogen-containing inhaled agents for general anesthesia it should be considered that during surgery the effect of blockade of β-adrenoreceptors may be eliminated by beta-adrenergic stimulators. As a rule, therapy with beta-adrenoblockers should not be discontinued, and abrupt withdrawal of the drug should be avoided in any case. The anesthesiologist should be informed about the treatment. If class IA antiarrhythmic drugs (quinidine, hydroquinidine and disopyramide) and class III (amiodarone, dofetilide, ibutilide, sotalol) are used simultaneously with Lokren, Certain phenothiazine neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine), benzamides (amisulpride, sulpiride, thiapride), butyrophenones (droperidol, haloperidol), other neuroleptics (pimozide), as well as cisapride, difemanil, erythromycin (for IV administration), halofantrine, misolastine, moxifloxacin, pentamidine, spiramycin (for IV administration) and vincamine (for IV administration) may increase the risk of ventricular arrhythmias, especially “pirouette” type (clinical and ECG monitoring is required if combined therapy is necessary). When concomitant use with propafenone, contractility, automaticity and conduction disorders may develop (due to the suppression of sympathetic compensatory mechanisms), which requires monitoring of the clinical condition and ECG. Co-administration with baclofen may increase the antihypertensive effect (BP control and dose adjustment if necessary is required). When concomitant use with insulin and oral hypoglycemic sulfonylurea derivatives, it should be taken into account that all beta-adrenoblockers may mask the symptoms of hypoglycemia (palpitations and tachycardia). The patient should be warned about the need to strengthen control of blood glucose levels, especially at the beginning of treatment. When concomitant use with cholinesterase inhibitors (donepezil, galantamine, ambenonium chloride, neostigmine, pyridostigmine, rivastigmine, tacrine), the risk of bradycardia may increase (additive effect), which requires control of the clinical condition. Co-administration with central antihypertensive agents (clonidine, apraclonidine, alpha-methyldopa, guanfacine, moxonidine, rilmenidine) may cause a significant increase in BP with abrupt withdrawal of central antihypertensive agent (avoid abrupt withdrawal of antihypertensive agent and monitor the clinical condition). When administered intravenously, lidocaine may increase plasma lidocaine concentration with a possible increase in adverse neurological symptoms and cardiovascular effects (reduced lidocaine metabolism in the liver), which requires monitoring of the clinical condition and ECG and possibly monitoring the plasma lidocaine concentration during treatment with beta-adrenoblockers and after its discontinuation. Adjustment of lidocaine dose if necessary.
Concurrent use with NSAIDs for systemic use (including selective COX-2 inhibitors) may decrease hypotensive effect (inhibition of prostaglandin synthesis and water and sodium retention). Concomitant use with calcium channel blockers may cause arterial hypotension, circulatory failure in patients with latent or uncontrolled heart failure. Treatment with beta-adrenoblockers may minimize reflex sympathetic mechanisms. When concomitant use with tricyclic antidepressants (like imipramine), neuroleptics may increase the hypotensive effect and the risk of orthostatic hypotension (additive effect). Concomitant use with mefloquine increases the risk of bradycardia (additive effect). Co-administration with dipyridamole (for intravenous administration) may increase the antihypertensive effect. Co-administration with alpha-adrenoblockers used in urology (alfuzosin, doxazosin, prazosin, tamsulosin, terazosin) increases the antihypertensive effect and increases the risk of orthostatic hypotension. Co-administration with amifostine may increase the 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 when administered intravenously increases the severity of cardiodepressive effects and the likelihood of BP decrease in patients receiving betaxolol. Co-administration of betaxolol decreases clearance of xanthines (except diphylline) and increases their plasma concentrations, especially in patients with initially increased clearance of theophylline (e.g. due to smoking). The hypotensive effect of betaxolol is weakened by estrogens (sodium retention). When used together with betaxolol, cardiac glycosides, methyldopa, reserpine and guanfacine increase the risk of developing or worsening bradycardia, AV-blockade, cardiac arrest. When co-administered with betaxolol, nifedipine, diuretics, clonidine, sympatholytics, hydralazine and other hypotensive drugs may lead to a significant decrease in BP. When used together, betaxolol prolongs the duration of action of nondepolarizing myorelaxants and increases the anticoagulant effect of coumarins. When concomitant use with betaxolol, ethanol, sedatives and hypnotics increase CNS depression. Concomitant use with MAO inhibitors is not recommended due to significant increase in hypotensive effect, a break in treatment between MAO inhibitors and betaxololol should be at least 14 days. When used together with betaxolol, unhydrogenated ergot alkaloids increase the risk of peripheral circulatory disorders.

Special Instructions

With caution use in hepatic failure.

Cautiously use in chronic renal failure, during hemodialysis. In patients with renal failure, the dose should be adjusted depending on the blood creatinine concentration or creatinine clearance (CK).

The treatment of patients with angina pectoris should never be stopped abruptly; abrupt withdrawal may lead to severe heart rhythm disturbances, myocardial infarction or sudden death.

Patients taking Lokren require monitoring, which should include monitoring for HR and BP (at the beginning of treatment daily, then once every 3-4 months), glucose content in diabetic patients (once every 4-5 months), monitoring of renal function in elderly patients (once every 4-5 months) is necessary. The patient should be trained in the method of heart rate calculation and instructed to consult a physician if the heart rate is less than 50 bpm.

In patients with CHD, the dose should be reduced gradually (over 1-2 weeks) and, if necessary, substitution therapy should be started simultaneously to avoid angina progression. In approximately 20% of angina patients beta-adrenoblockers are ineffective (the main reasons are severe coronary atherosclerosis with low threshold of ischemia and HR at the time of angina attack less than 100 bpm and increased left ventricular end-diastolic pressure, which impairs subendocardial blood flow).

If clonidine therapy is concomitant, it may not be discontinued until several days after withdrawal of Lochren.

Lokren should be discontinued before testing blood and urine catecholamines (catecholamines in blood, catecholamines in urine), normetanephrine (normetanephrine free in urine) and vanillinindalic acid; antinuclear antibody titers.

In bronchial asthma and chronic obstructive pulmonary disease, beta-adrenoblockers may be prescribed only if the disease is of moderate severity, with selection of a selective beta-adrenoblocker at a low starting dose. Respiratory function assessment is recommended before starting treatment. If seizures develop during treatment, bronchodilators (? 2 -adrenomimetics) may be used.

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

The dose of the drug should be reduced if the resting heart rate is below 50-55 bpm and the patient has clinical signs of bradycardia.

With regard to negative dromotropic effect of beta-adreno-blockers, caution should be exercised when using in AV blockade of degree I.

Beta-adrenoblockers may increase the number and duration of attacks in Prinzmetal angina. The use of cardioselective ? 1 -adrenoblockers is possible in less severe and mixed forms, provided that treatment is carried out in combination with vasodilators.

Beta-adrenoblockers may worsen the condition of patients with peripheral circulatory disorders (Raynaud’s disease or syndrome, arteritis or chronic obliterating diseases of the arteries of the lower extremities).

When using beta-adrenoblockers to treat arterial hypertension caused by pheochromocytoma, close monitoring of BP is required.

Patients with diabetes mellitus should be cautioned to increase self-monitoring of blood glucose levels at the start of treatment. Initial symptoms of hypoglycemia may be masked, especially tachycardia, palpitations, and sweating.

In psoriasis, a careful assessment of the need for the drug is required, as there have been reports of worsening of the course of the disease during treatment with beta-adrenoblockers.

In patients who are prone to severe anaphylactic reactions (especially those associated with the use of floktafenine or during desensitization) therapy with beta-adrenoblockers may lead to further worsening of reactions and reduction of treatment efficacy. Risk of anaphylactic reactions should be considered when using the drug.

In general anesthesia, it should be taken into account that beta-adrenoblockers mask reflex tachycardia and increase the risk of arterial hypotension. Continued therapy with beta-adrenoblockers reduces the risk of arrhythmias, myocardial ischemia, and hypertensive crises. The anesthesiologist should be informed that the patient has been treated with beta-adrenoblockers.

In elective surgery and when it is necessary to discontinue therapy with the drug, it should be noted that withdrawal of the drug for 48 h allows restoration of catecholamine sensitivity. Therapy with beta-adrenoblockers should not be interrupted in patients with coronary artery disease. It is recommended that therapy be continued until surgery, given the risk associated with abrupt withdrawal of beta-adrenoblockers. For emergency surgery or when discontinuation is not possible, the patient should be protected from the effects of vagus nerve excitation by appropriate premedication with atropine (with repetition if necessary). For general anesthesia, drugs with minimal negative inotropic effects should be used.

The symptoms of thyrotoxicosis may be masked by therapy with beta-adrenoblockers.

Athletes should be aware that the drug may react positively in doping control tests.

Alcohol should be avoided when using the drug.

Patients who wear contact lenses should be aware that tear fluid may decrease with treatment.

The effectiveness of beta-adrenoblockers is lower in smokers.

The treatment of elderly patients should be started with a low dose and under close supervision.

The drug should not be used in children because there is no clinical data about the efficacy and safety in this patient population.

Contraindications

– Chronic heart failure II B-III stages.
– Cardiogenic shock.
– AV-blockade of II and III degree (without connection of artificial pacemaker).
– Prinzmetal angina.
– CAD (including sinoatrial blockade).
– Severe bradycardia.
– Arterial hypotension.
– Cardiomegaly (without signs of heart failure).
– Concomitant use with sultopride and floktafenin.
– Concomitant use of MAO inhibitors.
– Age under 18 years (effectiveness and safety is not established).
– Hypersensitivity to betaxolol.
– The drug is contraindicated in congenital galactosemia, glucose/galactose absorption disorders or lactose deficiency (because it contains lactose).

With caution when using the drug in patients with a history of allergic reactions, in pheochromocytoma, metabolic acidosis, peripheral vascular obliterating diseases (intermittent claudication, Raynaud’s syndrome), liver failure, chronic renal failure, during hemodialysis, myasthenia, depression (including in history).

In elderly patients, in cases of AV-blockade of 1st degree, in chronic obstructive pulmonary disease (bronchial asthma, pulmonary emphysema), in patients with psoriasis, in chronic heart failure, thyrotoxicosis, diabetes.

Side effects

CNS and peripheral nervous system disorders: increased fatigue, weakness, dizziness, headache, drowsiness, insomnia, nightmares, depression, anxiety, confusion or short-term memory loss, hallucinations, asthenic syndrome, muscle weakness, paresthesias in extremities (in claudication, Raynaud’s syndrome), tremor.

Cardiovascular system disorders: sinus bradycardia, palpitations, orthostatic hypotension, myocardial conduction disorders, AV blockade (up to cardiac arrest), arrhythmias, impaired myocardial contractility, development (or worsening) of symptoms of heart failure (edema of ankles, feet, lower legs), marked BP decrease, angiospasm manifestation (decreased peripheral circulation, coldness of the lower extremities, Raynaud’s syndrome), chest pain.

Digestive system disorders: dry mucous membranes of the mouth, nausea, vomiting, abdominal pain, constipation or diarrhea, liver disorders (dark urine, jaundice of sclerae or skin, cholestasis), change of taste.

Respiratory system: nasal congestion, difficulty in breathing when prescribed in high doses (loss of selectivity); laryngo- and bronchospasm (in predisposed patients).

Senses: visual disturbances, decreased lacrimal gland secretion, dry and painful eyes, conjunctivitis.

Endocrine system disorders: hyperglycemia in patients with insulin-independent diabetes mellitus, hypoglycemia in patients receiving insulin, hypothyroidism.

Dermatological reactions: increased sweating, skin hyperemia, exanthema, psoriasis-like skin reactions, exacerbation of psoriasis.

Allergic reactions: skin rash, itching, urticaria.

Others: back pain, arthralgia, decreased libido, decreased potency, withdrawal syndrome (increased angina pectoris attacks, increased BP); rarely – appearance of antinuclear antibodies (only in exceptional cases accompanied by clinical manifestations such as SLE, which disappear when treatment is stopped).

Overdose

Symptoms: Severe bradycardia, Dizziness, Severe decrease in BP, Arrhythmias, ventricular extrasystoles, AV blockade, Syncope, Heart failure, Shortness of breath, bronchospasm, Cyanosis of finger and palm nails, Seizures.

Pregnancy use

There have been no teratogenic effects of Lokren in experimental animal studies. To date, no teratogenic effects have been observed in humans, and no congenital malformations have been observed in controlled prospective studies.

The use of the drug in pregnancy is possible only when the estimated benefit to the mother exceeds the potential risk to the fetus.

Betaxolol is slightly excreted with the breast milk. The risk of hypoglycemia or bradycardia in the child has not been investigated. If it is necessary to use Locren during lactation, discontinuation of breastfeeding should be considered.

Betaxolol has been found to affect the fetus (intrauterine growth retardation, hypoglycemia, bradycardia). In developing heart failure (decompensation) in newborns whose mothers have taken beta-adrenoblockers during pregnancy, they are admitted to an ICU; glucagon is prescribed at the rate of 0.3 mg/kg; isoprenaline and dobutamine are usually in sufficiently high doses and long-term, which requires close monitoring.

We should note that in newborns whose mothers have received beta-adrenoblockers, the effects of beta-adrenoblockers persist for several days after birth. Although this residual effect may have no clinical consequences, a cardiac defect may nevertheless develop, requiring intensive care in the newborn. In such a situation, the administration of solutions that increase the blood circulation (risk of acute pulmonary edema) should be avoided. There are also reports of bradycardia, respiratory distress syndrome and hypoglycemia. Therefore, close monitoring of newborns in specialized settings (monitoring HR and blood glucose levels during the first 3-5 days of life) is recommended.

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