Lokren - instructions for use, doses, side effects, contraindications

Active substance:
	Betaxolol hydrochloride	20.00 mg
Auxiliary substances, including the composition of the shell:
	Lactose Monohydrate	100.00 mg
	Sodium amylopectin glycolate
	Microcrystalline cellulose	113.00 mg
	Silica dioxide colloidal anhydrous	1.60 mg
	Magnesium stearate	1.40 mg
	Hypromellose	3.90 mg
	Macrogol-400	0.43 mg
	Titanium dioxide (E 171)	0.67 mg

Description:

White, biconcave, round tablets covered with a shell, with a dividing line on one side and engraving KE 20 on the other side.

Pharmacotherapeutic group:beta1-blocker selective

ATX: & nbsp

S.01.E.D.02 Betaxolol

Pharmacodynamics:

Betaxolol is characterized by three pharmacological properties:

- cardioselective beta-adrenergic blocking action;

- absence of partial agonistic activity (that is, it does not show its own sympathomimetic action);

- a weak membrane-stabilizing effect (like quinidine or local anesthetics) in concentrations exceeding therapeutic.

Pharmacokinetics:

Suction

The drug quickly and completely (100%) is absorbed from the gastrointestinal tract after ingestion, bioavailability is about 85%. The maximum concentration in the blood plasma is reached in 2-4 hours. Betaxolol binds to blood plasma proteins by about 50%.

Permeability through the blood-brain and placental barrier is low. Secretion of breast milk is insignificant.

Metabolism

The volume of distribution is about 6 l / kg. In organism betaxolol basically turns into inactive metabolites. The solubility in fats is moderate.

Excretion

It is excreted by the kidneys in the form of metabolites (more than 80%), 10-15% unchanged. The half-life (T_1/2) of betaxolol is 15-20 hours. T_1/2when the liver function is impaired by 33%, but the clearance does not change; with a violation of kidney function T_1/2doubles (lower doses are necessary).

It is not removed during hemodialysis.

Indications:

- Arterial hypertension;

- prevention of angina pectoris attacks.

Contraindications:

- Hypersensitivity to betaxolol;

- severe chronic heart failure IIB-III;

- cardiogenic shock;

- atrioventricular blockade of II and III degree (without connection of an artificial pacemaker);

- angina of Prinzmetal;

- syndrome of weakness of the sinus node (including sinoatrial blockade);

- severe bradycardia;

- arterial hypotension;

- combined therapy with sultopride and floktaphenin;

- simultaneous administration of monoamine oxidase inhibitors (MAO);

- cardiomegaly (no signs of heart failure);

- age to 18 years (efficacy and safety not established).

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

Carefully:

Allergic reactions in the anamnesis, pheochromocytoma, metabolic acidosis, obliterating peripheral vascular diseases ("intermittent" lameness, Raynaud's syndrome), hepatic insufficiency, chronic renal failure, hemodialysis, myasthenia gravis, depression (including history), elderly age, atrioventricular blockade I degree, chronic obstructive pulmonary disease (bronchial asthma, emphysema), psoriasis, chronic circulatory failure, thyrotoxicosis, diabetes mellitus.

Pregnancy and lactation:

Teratogenicity

There was no teratogenic effect of the drug in animal experiments. To date, no teratogenic effects have been observed in humans, and controlled prospective studies have not shown congenital malformations.

Application in pregnancy is possible only if the benefit to the mother exceeds the potential risk to the fetus and / or the child.

Breast-feeding

Beta-adrenoblockers penetrate into breast milk (see "Pharmacokinetic properties"). The risk of hypoglycemia or bradycardia has not been investigated, so breastfeeding during treatment should be discontinued.

Dosing and Administration:

The drug should be taken orally, not chewed, washed down with a sufficient amount of liquid.

The initial dose is 1 tablet (20 mg) per day.

Dosage in patients with renal insufficiency

The dose of the drug should be established in accordance with the function of the patient's kidneys: dose changes are not required when creatinine clearance is more than 20 ml / min. However, at the beginning of treatment it is recommended to conduct clinical observation until equilibrium levels of the drug in the blood are reached (on average 4 days).

In patients with severe renal insufficiency (creatinine clearance less than 20 ml / min), the recommended initial dose of the drug is 5 mg / day (in patients on hemodialysis - regardless of the frequency and timing of hemodialysis sessions).

Dosage in patients with hepatic impairment

In patients with hepatic insufficiency, dose changes are usually not required. However, at the beginning of therapy, a more thorough clinical observation of the patient is recommended.

Side effects:

Undesirable reactions are presented to the organ systems in accordance with the classification of the Medical Dictionary of Regulatory Activities (MedDRA). The incidence of side effects was determined in accordance with the classification of the World Health Organization: very often 10%; often ≥ 1% and <10%; infrequently ≥ 0.1% and <1%; rarely ≥ 0.01% and <0.1%; very rarely <0.1%; unknown frequency (it is not possible to determine the incidence of side effects from available data).

Disturbances from the skin and subcutaneous tissues

Rarely: skin reactions, including psoriasis-like rashes or exacerbation of psoriasis (see "With caution").

Unknown frequency: hives, itching, hyperhidrosis.

Disturbances from the nervous system

Often: dizziness, headache.

Very rarely: paresthesia in the distal parts of the limbs.

Unknown frequency: retardation.

Disturbances on the part of the organ of sight

Rarely: dry eyes.

Very rarely: visual impairment.

Disorders of the psyche

Often: asthenia, insomnia.

Rarely: depression.

Very rarely: hallucinations, confusion, nightmares.

Disorders from the gastrointestinal tract

Often: gastralgia, diarrhea, nausea, vomiting.

Disorders from the metabolism and nutrition

Very rarely: hypoglycemia, hyperglycemia.

Heart Disease

Often: bradycardia (possibly severe).

Rarely: the heartesevere insufficiency, marked decrease in arterial pressure, slowing of atrioventricular conduction or aggravation of atrioventricular blockade.

Vascular disorders

Often: decrease in cutaneous temperature of the upper and lower extremities.

Rarely: Raynaud's syndrome, increased peripheral circulatory disturbances, including "intermittent claudication".

Disturbances from the respiratory system, organs of the chest and mediastinum

Rarely: bronchospasm.

Violations of the genitals and mammary gland

Often: impotence.

Laboratory and instrumental data

Rarely: the appearance of antinuclear antibodies, only in exceptional cases, combined with the clinical manifestations of lupus-like syndrome, disappearing after discontinuation of the drug.

Overdose:

Symptoms: pronounced bradycardia, dizziness,atrioventricular blockade, 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 absorbents;

in the case of a bradycardia or an excessive decrease in blood pressure, the following measures should be applied:

- atropine 1-2 mg intravenously;

- 1 mg glucagon with repetition if necessary;

- accompanied, if necessary, by a slow infusion of 25 μg of isoprenaline or by the administration of dobutamine 2.5-10 μg / kg / min.

In the case of heart failure (decompensation) in newborns, whose mothers during pregnancy were taking beta-blockers:

- glucagon at the rate of 0.3 mg / kg;

- hospitalization in the intensive care unit;

- isoprenaline and dobutamine: usually in high enough doses and for a long time, which requires observation by a specialist.

Interaction:

Contraindicated combinations

With floktaphenin

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

With sultopride

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

Unrecommended combinations

With amiodarone

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

With cardiac glycosides

Risk of development or aggravation of bradycardia, atrioventricular blockade, cardiac arrest.

With MAO inhibitors

It is not recommended simultaneous use with MAO inhibitors 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.

FROM phingolymode

As a result of a possible increase in bradycardia, treatment with phygolyimode Mr.e should be started in patients receiving beta-blockers. If treatment with phynolyimod is considered necessary, appropriate monitoring is recommended at the beginning of treatment, at least within 24 hours.

Combinations that should be used from caution

With blockers of "slow" calcium channels (beprideal, diltiazem, mibefradil and verapamil)

Violations of automatism (pronounced bradycardia, stop of sinus node), violations of atrioventricular conduction, heart failure [synergistic (mutually amplifying) effects]. Such a combination can only be used under careful clinical and electrocardiographic observation, especially in elderly patients or at the beginning of treatment.

FROM iodine-containing contrast agents

In the case of shock or a sharp decrease in blood pressure with the introduction of iodine-containing contrast agents, beta-adrenoblockers reduce compensatory cardiovascular reactions. If possible, before carrying out radiographic Studies using iodine-containing contrast agents should discontinue beta-blocker treatment.

With inhaled halogenated anesthetics

Beta-adrenoblockers have cardiodepressant action (inhibition of beta-adrenergic receptors can be reduced by 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.An anesthesiologist should be informed of the use of the beta-blocker.

With preparations, The ability to cause ventricular arrhythmias, including ventricular tachycardia such as "pirouette: antiarrhythmic drugs of class IA (quinidine, hydroquinidine and disopyramide) and class III (amiodarone, dofetilide, ibutilide), sotalol, some neuroleptics from the phenothiazine group (chlorpromazine, cyamemazine, levomepromazine, thioridazine), benzamides (amisulppid, sulpiride, tiapride), butyrophenones (droperidol, haloperidol), other neuroleptics (pimozide) and other drugs (cisapride, difemanyl administered intravenously erythromycin, halofantrine, misolastine, moxifloxacin, pentamidine, intravenously administered spiramycin and administered intravenously wincamine)

Increased risk of ventricular arrhythmias, in particular ventricular pirouette tachycardia. Clinical and electrocardiographic monitoring is required.

With propaphenone

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

With baclofen

Increased antihypertensive action of betaxolol. It is necessary to monitor BP and dose adjustment of betaxolol in case of need.

With insulin and hypoglycemic agents for oral administration, derivatives of sulfonylureas (see the sections "With caution", "Side effect", "Special instructions")

All beta-blockers can mask certain symptoms of hypoglycemia, such as palpitations and tachycardia.

The patient should be warned about the need to strengthen regular monitoring of blood glucose concentration, including active self-monitoring by the patient, especially at the beginning of treatment.

With cholinesterase inhibitors (ambenium, donepezil, galantamine, neostigmine, pyridostigmine, rivastigmine, Tacrine).

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

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

Increased risk of bradycardia, atrioventricular conductivity. A significant increase in BP with a sharp reversal of the antihypertensive agent of central action.It is necessary to avoid a sharp abolition of the antihypertensive agent and to carry out clinical control.

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

An increase in the concentration of lidocaine in blood plasma with a possible increase in unwanted neurological symptoms and effects from the cardiovascular system (reduced metabolism of lidocaine in the liver). Clinical and electrocardiographic observation and, possibly, control of lidocaine concentration in the blood plasma during treatment with beta-blockers and after its termination. If necessary, the dose of lidocaine is corrected.

Combinations that should be taken into account

With non-steroidal anti-inflammatory drugs (NSAIDs) (drugs with systemic action), including selective inhibitors of cyclooxygenase-2 (COX-2)

Decrease in antigipertenzithe effect of betaxolol (inhibition of synthesis prostaglandins NSAIDs and water retention and sodium pyrazolone derivatives).

With blockers of "slow" calcium channels from the dihydropyridine group

The mutual enhancement of the antihypertensive effect of blockers of "slow" calcium channels and betaxolol,the development of heart failure in patients with latent-flowing heart failure or uncontrolled heart failure. Treatment with beta-blockers can minimize the reflex activation of the sympathetic nervous system in response to vasodilation due to the blockers of the "slow" calcium channels from the dihydropyridine group.

With tricyclic antidepressants (such as imipramine), antipsychotics

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

With mefloquine

Risk of bradycardia (additive effect).

With dipyridamole (intravenous administration)

Increased antihypertensive effect of betaxolol.

With alpha-adrenoblockers, including those used in urology (alfuzosin, doxazosin, prazozin, tamsulosin, terazosin)

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

With amifostine

Increased antihypertensive effect of betaxolol.

With allergens, Used for immunotherapy or extracts of allergens for skin tests

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

With phenytoin (intravenous administration)

Increase in severity cardiodepressive action 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 elevated clearance of theophylline (for example, under the influence of smoking).

With estrogens

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

With glucocorticosteroids and tetracosactide

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

With diuretics

There may be an excessive decrease in blood pressure.

FROM Nondepolarizing muscle relaxants

Betaxolol lengthens the action nondepolarizing muscle relaxants.

With coumarins

Strengthening the anticoagulant effect of coumarins.

FROM ethanol (alcohol), sedatives and hypnotics

Increased central nervous system depression.

With unhydrogenated ergot alkaloids

Unhydrated ergot alkaloids increase the risk of peripheral circulatory disturbances when taking betaxolol.

Special instructions:

Treatment of patients with angina pectoris should never be interrupted abruptly: sudden 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 (at the beginning of treatment daily, then once every 3-4 months), glucose in diabetic patients (once every 4-5 months), it is necessary to monitor the function of the kidneys in elderly patients (once every 4-5 months).

It is necessary to teach the patient how to calculate heart rate and instruct about the need for medical consultation at a heart rate of less than 50 beats per minute.

Treatment should not be stopped abruptly, especially in patients with ischemic heart disease. The dose should be reduced gradually, that is, within 1-2 weeks, and, if necessary, it is possible to simultaneously start substitution therapy to avoid the progression of angina pectoris.

Approximately in 20% of patients with angina pectoris beta-adrenoblockers are ineffective.The main causes are severe coronary atherosclerosis with a low threshold of ischemia (heart rate at the time of development of an anginal attack less than 100 beats / min) and increased end-diastolic pressure of the left ventricle, which breaks the subendocardial blood flow.

With the simultaneous administration of clonidine, its administration may be discontinued only a few days after the withdrawal of Lokren®.

Lokren should be discontinued before the study of blood and urine levels of catecholamines, normetanephrine and vanillin-mandelic acid; titers of antinuclear antibodies.

Bronchial asthma and chronic obstructive pulmonary disease

Beta-adrenoblockers can be prescribed only to patients with moderate disease severity, with the choice of a selective beta-blocker in a low initial dose. Before the start of treatment it is recommended to perform an evaluation of the function of breathing.

When developing seizures during treatment, bronchodilators - β₂-adrenomimetics.

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 heart rate at rest is below 50-55 beats per minute and the patient has clinical manifestations of bradycardia.

Atrioventricular block of degree I

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

Angina pectoris

Beta-adrenoblockers can increase the number and duration of seizures in patients suffering from Prinzmetal angina. Use of cardioselective beta₁-adrenoconcretors is possible in less severe and mixed forms, provided that the treatment is performed in combination with vasodilators.

Violations of peripheral circulation

Beta-adrenoblockers can lead to worsening of patients with peripheral circulatory disorders (Raynaud's disease or Raynaud's syndrome, arteritis or chronic obliterating diseases of lower limb arteries).

Pheochromocytoma

In the case of using beta-adrenoblockers in the treatment of arterial hypertension caused by pheochromocytoma, careful monitoring of blood pressure is required.

Elderly patients

Treatment of elderly patients should start with a small dose and under strict supervision.

Patients with renal insufficiency

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

Patients with diabetes mellitus

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

Psoriasis

It requires a careful assessment of the need for prescribing, since 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 floktaphenin or during desensitization, beta-blocker therapy may lead to further intensification of reactions and a decrease in the effectiveness of treatment.

General anesthesia

Beta-adrenoblockers mask reflex tachycardia and increase the risk of developing arterial hypotension. Continued therapy with beta-blockers reduces the risk of arrhythmia,myocardial ischemia and hypertensive crises. An anesthesiologist should be informed that the patient was receiving beta-blocker therapy.

If cessation of treatment is deemed necessary, then it is considered that cessation of therapy for 48 hours allows to restore sensitivity to catecholamines.

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

- the patients with coronary insufficiency it is desirable to continue treatment up to the operation, taking into account the risk associated with the sudden abolition of beta-blockers;

- at in case of emergency operations or in cases when cessation of treatment is not possible, the patient should be protected from the effects of excitation of the vagus nerve by appropriate premedication with atropine, with repetition if necessary. For general anesthesia, it is necessary to use substances that are least depressing myocardium.

The risk of developing anaphylactic reactions should be considered.

Thyrotoxicosis

Symptoms of thyrotoxicosis can be masked by therapy with beta-blockers.

Athletes

Athletes should consider that the drug contains an active substance,which can give a positive reaction when conducting doping tests.

For the duration of treatment, exclude the use of ethanol.

Patients using contact lenses should take into account that the tear fluid can be reduced against the background of treatment.

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

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

Form release / dosage:

Tablets, film-coated, 20 mg.

Packaging:

For 14 tablets in a blister of PVC and aluminum foil.

For 2 or 4 blisters together with instructions for use in a cardboard box.

Storage conditions:

At a temperature below 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012715 / 01

Date of registration:16.09.2011

The owner of the registration certificate:Sanofi-Aventis FranceSanofi-Aventis France France

Manufacturer: & nbsp

SANOFI WINTHROP INDUSTRIE France

Representation: & nbspSanofi Aventis GroupSanofi Aventis Group

Information update date: & nbsp03.04.2018

Illustrated instructions

Instructions

Lokren® (Lokren®)