Lokren, 20mg pills, 56pcs

Composition

1 coated tablet contains: Betaxolol hydrochloride 20 mg,

Auxiliary substances:

lactose monohydrate-100 mg,

microcrystalline cellulose-113 mg,

sodium carboxymethyl starch (type A) – 4 mg,

colloidal silicon dioxide-1.6 mg,

magnesium stearate-1.4 mg.

Shell composition:

hypromellose – 3.9 mg,

macrogol 400-0.43 mg,

titanium dioxide (E 171) – 0.67 mg

Pharmacological action

Selective beta_-1-adrenoblocker. Betaxolol is characterized by three pharmacological properties: cardioselective beta_-1-adrenoblocking effect; lack of partial agonist activity (lack of internal sympathomimetic activity); weak membrane-stabilizing effect (similar to the action of quinidine or local anesthetics) in concentrations exceeding therapeutic.

It should be noted that the selective effect of betaxolol β₁-adrenergic receptors is not absolute, as when applied in high doses may impact betaxolol β₂-adrenergic receptor, located mainly in the smooth muscles of the bronchi and blood vessels (betaxolol however, the effects on β₂-adrenergic receptors is much weaker than that in the non-selective beta blockers).

When using betaxolol, its beta_-1-adrenergic blocking activity is manifested by the following pharmacodynamic effects:

• the decrease in heart rate at rest and during exercise (due to blockade of β-adrenergic receptors in the sinus node, which, combined with the absence of betaxolol intrinsic sympathomimetic activity leads to a slowing of sinus node automaticity);
• a decrease in cardiac output at rest and during exercise due to competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic nerve endings;
• systolic and diastolic blood pressure at rest and during exercise (the mechanism of the antihypertensive action described below);
• reduction of reflex orthostatic tachycardia.

As a result of these effects, there is a decrease in the load on the heart at rest and during physical exertion.

The mechanism of antihypertensive action of beta-blockers is not fully established.

Beta-blockers are supposed to have the following mechanisms of antihypertensive action: :

• reduction of cardiac output;
• elimination of spasm of peripheral arteries (due to central action, leading to a decrease in sympathetic impulses to the periphery, to the vessels, and due to inhibition of renin activity).

The antihypertensive effect of betaxolol does not decrease with prolonged use. With a single daily intake of betaxolol (from 5 to 40 mg), the antihypertensive effect is the same after 3-4 hours (the time to reach the_cmax of betaxolol in the blood) and after 24 hours (before taking the next dose). When taking 5 mg and 10 mg of betaxolol, its antihypertensive effect is, respectively,50% and 80% of the antihypertensive effect when taking 20 mg of betaxolol.

Thus, in the dose range of 5-20 mg, there is a dose-dependent antihypertensive effect, and with an increase in the dose from 10 mg to 20 mg, the increase in the antihypertensive effect is insignificant. Increasing the dose from 20 mg to 40 mg does little to alter the antihypertensive effect of betaxolol. The maximum antihypertensive effect of each betaxolol dose is achieved after 1-2 weeks.

Unlike the antihypertensive effect of betaxolol, the effect of reducing heart rate with increasing its dose (from 10 mg to 40 mg) does not increase.

In addition, betaxolol can slow down the conductivity of the AV node.

Indications

• arterial hypertension (in monotherapy and combination therapy);
• prevention of angina attacks of tension (in monotherapy and combination therapy).

Contraindications

Use the drug with caution:

• in bronchial asthma and chronic obstructive pulmonary disease moderate severity (to begin treatment with small doses, and preferably under the control of the parameters of respiratory function; thanks to the beta₁-selectivity betaxolol in the event of an attack of bronchial asthma on the background of his admission possible relief of attack beta₂-agonists);
• in chronic heart failure in the stage of compensation (treatment with betaxolol is possible only under strict medical supervision; treatment should begin with very small doses, with gradual increase);
• with AV blockade of I degree (requires careful observation, including ECG monitoring);
• when occlusive peripheral artery disease, Raynaud’s syndrome (except severe) (possibly increasing violations of the peripheral circulation);
• Prinzmetal angina (possibly strokes; the use of selective beta₁-adrenoreceptor is only possible with the simultaneous use of vasodilators);
• when treated pheochromocytoma (in drug treatment of Lokren®arterial hypertension on the background of pheochromocytoma patients requires careful monitoring of blood pressure parameters);
• patients of advanced age (must begin treatment with small doses and under careful medical supervision);
• in renal failure (KK in more than 20 ml/min, careful observation of the patient during the first 4 days of treatment; with CC less than 20 ml/min and/or hemodialysis is required correction mode);
• when liver failure (requires more careful clinical observation at the beginning of treatment);
• patients with diabetes mellitus (requires regular monitoring of glucose concentration in the blood, including active self-monitoring by the patient at the beginning of treatment; it is possible to reduce the severity of signs of hypoglycemia, such as tachycardia, palpitations, and increased sweating);
• psoriasis (beta-blockers may aggravate the course of psoriasis);
• when conducting desensitizing therapy.

Side effects

Allergic reactions:  skin rash, pruritus, urticaria.

The following side effects are listed according to the following frequency gradations: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10 000, <1/1000); very rare (

Dermatological reactions:  rarely – various skin reactions, including skin rash, pruritus, urticaria, psoriasis-like rashes, or exacerbation of psoriasis.

Nervous system disorders:  often – dizziness, headache, asthenia, insomnia; rarely-depression; very rarely-hallucinations, confusion, nightmares, paresthesia.

From the side of the visual organ:  rarely-dry eyes, decreased intraocular pressure (due to the possibility of its reduction under the influence of beta-blockers); very rarely-visual disturbances.

From the digestive system:  often – gastralgia, diarrhea, nausea, vomiting.

From the side of metabolism:  very rarely – hypoglycemia, hyperglycemia.

From the cardiovascular system:  often-bradycardia, possibly severe, a decrease in skin temperature of the upper and lower extremities; rarely-the development (or aggravation)of symptoms of heart failure (swelling of the ankles, feet, shins), a pronounced decrease in blood pressure, slowing AV conduction, manifestations of angiospasm: Raynaud’s syndrome, increased peripheral circulatory disorders, including intermittent claudication, increased angina attacks.

Respiratory system disorders:  rarely-bronchospasm.

From the genitals:  often-impotence.

From the side of laboratory parameters:  rarely-the appearance of antinuclear antibodies, only in exceptional cases combined with clinical manifestations of lupus-like syndrome, which passes after discontinuation of treatment.

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

Other services:  withdrawal syndrome (increased or more frequent angina attacks, increased blood pressure).

Interaction

Contraindicated combinations

With floctafenin

In the case of shock or hypotension caused by floctafenin, beta-blockers cause a decrease in compensatory cardiovascular reactions.

With sultoprid

Violations of the automatism of the heart (pronounced bradycardia) due to an additional decrease in heart rate.

Not recommended combinations

With amiodarone

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

With slow calcium channel blockers (bepridil, diltiazem and verapamil)

Automatism disorders (severe bradycardia, sinus node arrest), AV conduction disorders, heart failure (synergistic / mutually reinforcing / effects).

This combination can only be used under close clinical and ECG monitoring, especially in elderly patients or at the beginning of treatment.

With cardiac glycosides

, the risk of developing or worsening bradycardia, AV block, or cardiac arrest.

With MAO inhibitors

Concomitant use with MAO inhibitors is not recommended due to a significant increase in the antihypertensive effect of betaxolol, a break in treatment between taking MAO inhibitors and betaxolol should be at least 14 days.

With iodine-containing 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, then before conducting an X-ray examination with the use of iodine-containing contrast agents, treatment with a beta-blocker should be discontinued.

Combinations that should be used with caution

With inhaled halogen-containing anesthetics

, Beta-blockers have a cardiodepressive effect (inhibition of beta-adrenergic receptors can be reduced with the introduction of beta-adrenostimulants). As a rule, treatment with beta-blockers does not stop and in any case, abrupt withdrawal of beta-blockers should be avoided. The anesthesiologist should be informed about taking a beta-blocker.

Drugs that can cause ventricular arrhythmias, including ventricular tachycardia type “pirouette”: antiarrhythmic agents class IA (quinidine, gedragingen and disopyramide) and class III (amiodarone, dofetilide, ibutilide), sotalol, some antipsychotics from the group of phenothiazine (chlorpromazine, cyamemazine, levomepromazine, thioridazine), benzamide (amisulpride, sulpiride, tiapride), butyrophenones (droperidol, haloperidol), other neuroleptics (pimozide) and other drugs (cisapride, have diphemanil entered into/to erythromycin, halofantrine, mizolastine, moxifloxacin, pentamidine, enter in/in spiramycin and enter in/in vincamine has

Increased risk of ventricular arrhythmias, in particular ventricular tachycardia of the “pirouette” type. Clinical and ECG monitoring is required.

With propafenone

Disorders of contractility, automatism, and conduction (suppression of sympathetic compensatory mechanisms). Clinical and ECG monitoring is required.

With baclofen

Increased antihypertensive effect of betaxolol. It is necessary to monitor blood pressure and adjust the dose of betaxolol if necessary.

With insulin and hypoglycemic agents for oral use, sulfonylureas

All beta-blockers can 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 (ambenonium, donepezil, galantamine, neostigmine, pyridostigmine, rivastigmine, tacrin)

Risk of increased bradycardia (additive effect). Regular clinical monitoring is required.

With antihypertensive agents of central action (clonidine, apraclonidine, alpha-methyldopa, guanfacine, moxonidine, rilmenidine)

Increased risk of developing bradycardia, impaired AV conduction. A significant increase in blood pressure with a sharp withdrawal of a central antihypertensive agent. Abrupt withdrawal of the antihypertensive agent should be avoided and clinical monitoring should be carried out.

With lidocaine 10% solution (IV as an antiarrhythmic agent)

An increase in the concentration of lidocaine in blood plasma with a possible increase in undesirable neurological symptoms and effects from the cardiovascular system (decreased metabolism of lidocaine in the liver). Clinical and ECG monitoring and possibly monitoring of lidocaine plasma concentrations are recommended during and after beta-blocker treatment. If necessary, adjust the dose of lidocaine.

Combinations to take into account

With NSAIDs (drugs with systemic action), including selective COX-2 inhibitors

Reduction of the antihypertensive effect of betaxolol (inhibition of prostaglandin synthesis by NSAIDs and retention of water and sodium by pyrazolone derivatives).

With slow calcium channel blockers from the dihydropyridine group

Mutual enhancement of the antihypertensive effect of slow calcium channel blockers and betaxolol, the development of heart failure in patients with latent heart failure or uncontrolled heart failure. Treatment with beta-blockers can minimize the reflex activation of the sympathetic nervous system in response to vasodilation under the influence of slow calcium channel blockers from the dihydropyridine group.

With tricyclic antidepressants (such as imipramine), neuroleptics

Increased antihypertensive effect of betaxolol and the risk of orthostatic hypotension (additive effect).

With mefloquine

, the risk of bradycardia (additive effect).

With dipyridamole (intravenous use)

Increased antihypertensive effect of betaxolol.

With alpha-blockers, including those used in urology (alfuzosin, doxazosin, prazosin, tamsulosin, terazosin)

Increased antihypertensive effect of betaxolol. Increased risk of orthostatic hypotension.

With amifostin

Increased antihypertensive effect of betaxolol.

With allergens used for immunotherapy or allergen extracts for skin tests

Increased risk of severe systemic allergic reactions or anaphylaxis in patients receiving betaxolol.

With phenytoin (intravenous use)

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 blood plasma, especially in patients with initially increased clearance of theophylline (for example, under the influence of smoking).

With estrogens

Weakening of the antihypertensive effect of betaxolol (sodium and water retention).

With GCS and tetracosactide

Weakening of the antihypertensive effect of betaxolol (sodium and water retention).

With diuretics

Excessive lowering of blood pressure is possible.

With non-depolarizing muscle relaxants

Betaxolol prolongs the action of non-depolarizing muscle relaxants.

With coumarins

Increased anticoagulant effect of coumarins.

With alcohol( ethanol), sedatives and sleeping pills

Increased CNS depression.

With unhydrogenated ergot alkaloids

Non-hydrogenated ergot alkaloids increase the risk of developing peripheral circulatory disorders when taking betaxolol.

How to take, course of use and dosage

The drug is taken orally and washed down with a sufficient amount of liquid. Do not chew the tablet.

The initial dose of Locren® for both indications for the use of the drug is usually 10 mg (1/2 tab. 20 mg). If the target BP values are not reached within 7-14 days of treatment, the dose is doubled to 20 mg / day.

Usually, doses of Locren® exceeding 20 mg are not used (due to the fact that when the dose is increased more than 20 mg, there is no statistically significant increase in the antihypertensive effect of the drug).

The maximum daily dose of Locren® is 40 mg.

In patients with renal insufficiency, dose adjustment is recommended depending on the functional state of the patient’s kidneys. If creatinine clearance exceeds 20 ml / min, no dose adjustment is required. However, at the beginning of treatment, it is recommended to conduct clinical monitoring until the equilibrium concentration of the drug in the blood is reached (which is achieved on average by 4-7 days of treatment). With severe renal insufficiency (creatinine clearance less than 20 ml / min), the recommended initial dose of the drug is 5 mg/day (regardless of the frequency and days of the hemodialysis procedure in patients undergoing hemodialysis), which, if insufficiently effective, can increase 2 times every 1-2 weeks. The maximum daily dose is 20 mg.

In patients with hepatic insufficiency, dose adjustment is usually not required. However, at the beginning of therapy, more careful clinical monitoring of the patient is recommended.

Overdose

Symptoms: severe bradycardia, dizziness, AV block, marked decrease in blood pressure, arrhythmias, ventricular extrasystole, syncope, heart failure, difficulty breathing, bronchospasm, cyanosis of the fingernails and palms, convulsions.

Treatment: gastric lavage, the appointment of absorbent material; in the case of bradycardia, it is recommended atropine 1-2 mg IV; then (if necessary) slow infusion of 25 µg of isoprenaline or infusion dobutamine 2.5-10 µg/kg/min; sometimes you may need a temporary setting of an artificial pacemaker; in the case of excessive blood pressure reduction is recommended in/in the introduction of plasma-substituting solutions and vasopressor drugs; with bronchospasm – the purpose of bronchodilators, including beta₂– adrenomimetics and / or aminophylline; in case of heart failure (decompensation) in newborns whose mothers took beta-blockers during pregnancy, hospitalization in the intensive care unit is recommended, isoprenaline and dobutamine – for a long time and