Concor core - official instructions for use. What are Concor tablets for and in what cases is it best to use them?

Compound

Description of the dosage form

White, heart-shaped, biconvex, film-coated tablets with a score line on both sides.

pharmachologic effect

Pharmacodynamics

A selective beta 1-blocker, without its own sympathomimetic activity, does not have a membrane-stabilizing effect. It has only slight affinity for beta 2 -adrenergic receptors of the smooth muscles of the bronchi and blood vessels, as well as for beta 2 -adrenergic receptors involved in the regulation of metabolism. Therefore, bisoprolol generally does not affect airway resistance and metabolic processes in which beta 2 adrenoreceptors are involved. The selective effect of the drug on beta 1-adrenergic receptors persists beyond the therapeutic range.

When used once in patients with coronary artery disease without signs of CHF, bisoprolol reduces heart rate, stroke volume and, as a result, reduces the ejection fraction and myocardial oxygen demand. With long-term therapy, the initially elevated TPR decreases.

Pharmacokinetics

Suction. Bisoprolol is almost completely (more than 90%) absorbed from the gastrointestinal tract. Its bioavailability due to negligible first-pass metabolism (at approximately 10%) is approximately 90% after oral administration. Food intake does not affect bioavailability. Bisoprolol exhibits linear kinetics, with its plasma concentrations being proportional to the dose taken in the range from 5 to 20 mg. Cmax in the blood is reached 2-3 hours after oral administration.

Distribution. Bisoprolol is distributed quite widely. Vd is 3.5 l/kg. The binding to plasma proteins reaches approximately 30%.

Metabolism. Metabolized via the oxidative pathway without subsequent conjugation. All metabolites are polar (water-soluble) and are excreted by the kidneys. The main metabolites found in blood plasma and urine do not exhibit pharmacological activity. Data obtained from experiments with human liver microsomes in vitro, show that bisoprolol is metabolized primarily by the CYP3A4 isoenzyme (about 95%), and the CYP2D6 isoenzyme plays only a small role.

Excretion. The clearance of bisoprolol is determined by the balance between excretion by the kidneys unchanged (about 50%) and metabolism in the liver (about 50%) to metabolites, which are then also excreted by the kidneys. The total clearance is 15 l/h. T 1/2 - 10-12 hours.

There is no information on the pharmacokinetics of bisoprolol in patients with CHF and concurrent impairment of liver or kidney function.

Indications for the drug Concor ® Cor

Chronic heart failure.

Contraindications

hypersensitivity to bisoprolol or any of the excipients (see “Composition”);

acute heart failure, chronic heart failure in the stage of decompensation, requiring inotropic therapy;

cardiogenic shock;

atrioventricular (AV) block II and III degrees without a pacemaker;

sick sinus syndrome;

sinoatrial block;

severe bradycardia (heart rate less than 60 beats/min);

severe arterial hypotension (sBP less than 100 mmHg);

severe forms of bronchial asthma;

severe peripheral arterial circulation disorders or Raynaud's syndrome;

pheochromocytoma (without simultaneous use of alpha-blockers);

metabolic acidosis;

age under 18 years (insufficient data on effectiveness and safety in this age group).

Carefully: carrying out desensitizing therapy; Prinzmetal's angina; hyperthyroidism; type 1 diabetes mellitus and diabetes mellitus with significant fluctuations in blood glucose concentrations; AV blockade, first degree; severe renal failure (creatinine Cl less than 20 ml/min); severe liver dysfunction; psoriasis; restrictive cardiomyopathy; congenital heart defects or heart valve disease with severe hemodynamic disturbances; CHF with myocardial infarction within the last 3 months; severe forms of chronic obstructive pulmonary disease; strict diet.

Use during pregnancy and breastfeeding

During pregnancy, Concor ® Cor should be recommended for use only if the benefit to the mother outweighs the risk of side effects in the fetus and/or child.

In general, beta blockers reduce blood flow to the placenta and may affect fetal development. Blood flow in the placenta and uterus should be monitored, as well as the growth and development of the unborn child should be monitored and alternative therapeutic measures should be taken if adverse events occur in relation to pregnancy and/or the fetus.

The newborn should be carefully examined after birth. In the first three days of life, symptoms of bradycardia and hypoglycemia may occur.

There is no data on the excretion of bisoprolol into breast milk. Therefore, taking the drug Concor ® Cor is not recommended for women during breastfeeding. If taking the drug during lactation is necessary, breastfeeding should be discontinued.

Side effects

The frequency of the adverse reactions listed below was determined according to the following: very often ≥1/10; often ≥1/100,<1/10; нечасто ≥1/1000, <1/100; редко ≥1/10000, <1/1000; очень редко < 1/10000.

From the side of the central nervous system: often - dizziness, headache; rarely - loss of consciousness.

General violations: often - asthenia, increased fatigue.

Mental disorders: infrequently - depression, insomnia; rarely - hallucinations, nightmares.

From the side of the organ of vision: rarely - decreased lacrimation (should be taken into account when wearing contact lenses); very rarely - conjunctivitis.

On the part of the hearing organ: rarely - hearing impairment.

From the SSS side: very often - bradycardia; often - worsening symptoms of CHF; a feeling of coldness or numbness in the extremities, a pronounced decrease in blood pressure; infrequently - impaired AV conduction, orthostatic hypotension.

From the respiratory system: uncommon - bronchospasm in patients with bronchial asthma or a history of airway obstruction; rarely - allergic rhinitis.

From the digestive tract: often - nausea, vomiting, diarrhea, constipation; rarely - hepatitis.

From the musculoskeletal system: Uncommon: muscle weakness, muscle cramps.

From the skin: rarely - hypersensitivity reactions, such as itching, rash, hyperemia of the skin; very rarely - alopecia. Beta blockers may worsen psoriasis symptoms or cause a psoriasis-like rash.

From the reproductive system: rarely - potency disorders.

Laboratory indicators: rarely - increased concentration of triglycerides and activity of hepatic transaminases in the blood (AST), (ALT).

Interaction

The effectiveness and tolerability of bisoprolol may be affected by the simultaneous use of other drugs. Such interaction can also occur in cases where two drugs are taken after a short period of time. The doctor must be informed about taking other drugs, even if they are taken without a doctor’s prescription (i.e., over-the-counter drugs).

Class I antiarrhythmic drugs(for example, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone), when used simultaneously with bisoprolol, can reduce AV conductivity and cardiac contractility.

CCBs such as verapamil and to a lesser extent diltiazem when used simultaneously with bisoprolol, they can lead to a decrease in myocardial contractility and impaired AV conduction. In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV blockade.

Centrally acting antihypertensives(such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to a decrease in heart rate and cardiac output, as well as vasodilation due to a decrease in central sympathetic tone. Abrupt withdrawal, especially before discontinuation of beta-blockers, may increase the risk of rebound hypertension.

Combinations requiring special caution

BPC, dihydropyridine derivatives(for example, nifedipine, felodipine, amlodipine), when used simultaneously with bisoprolol, may increase the risk of developing arterial hypotension. In patients with CHF, the risk of subsequent deterioration in cardiac contractility cannot be excluded.

Class III antiarrhythmic drugs(eg amiodarone) may increase AV conduction disturbances.

Effect of beta-blockers for topical use(for example, eye drops for the treatment of glaucoma) may enhance the systemic effects of bisoprolol (lowering blood pressure, lowering heart rate).

Parasympathomimetics when used simultaneously with bisoprolol, they can increase the impairment of AV conduction and increase the risk of developing bradycardia.

Hypoglycemic effect of insulin or oral hypoglycemic agents may intensify. Signs of hypoglycemia - in particular tachycardia - may be masked or suppressed. Such interactions are more likely when using non-selective beta-blockers.

Means for general anesthesia may increase the risk of cardiodepressive effects, leading to arterial hypotension (see "Special Instructions").

Cardiac glycosides when used simultaneously with bisoprolol, they can lead to an increase in impulse conduction time, and thus to the development of bradycardia.

NSAIDs may reduce the hypotensive effect of bisoprolol.

The simultaneous use of Concor ® Cor with beta-agonists (for example, isoprenaline, dobutamine) may lead to a decrease in the effect of both drugs.

The combination of bisoprolol with adrenergic agonists that affect beta and alpha adrenergic receptors (for example, norepinephrine, epinephrine) may enhance the vasoconstrictor effects of these drugs that occur with the participation of alpha adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely when using non-selective beta-blockers.

Antihypertensive drugs as well as other drugs with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines) may enhance the hypotensive effect of bisoprolol.

Mefloquine when used simultaneously with bisoprolol, it may increase the risk of bradycardia.

MAO inhibitors (except MAO-B inhibitors) may enhance the hypotensive effect of beta-blockers. Concomitant use may also lead to the development of a hypertensive crisis.

Directions for use and doses

Inside, 1 time per day, in the morning before, during or after breakfast, with a small amount of liquid. The tablets should not be chewed or crushed into powder.

The standard treatment regimen for CHF includes the use of ACE inhibitors or ARA II (in case of intolerance to ACE inhibitors), beta-blockers, diuretics and, optionally, cardiac glycosides. Initiation of treatment for CHF with Concor ® Cor requires a special titration phase and regular medical supervision.

The precondition for treatment with Concor ® Cor is stable CHF without signs of exacerbation.

Treatment of CHF with Concor ® Cor begins in accordance with the following titration scheme. This may require individual adaptation depending on how well the patient tolerates the prescribed dose, i.e. The dose can only be increased if the previous dose was well tolerated.

The recommended starting dose is 1.25 mg once daily. Depending on individual tolerance, the dose should be gradually increased to 2.5; 3.75; 5; 7.5 and 10 mg 1 time per day. Each subsequent dose increase should be carried out at least 2 weeks later.

If increasing the dose of the drug is poorly tolerated by the patient, a dose reduction may be possible. The maximum recommended dose for CHF is 10 mg of Concor ® Cor 1 time per day.

If the patient does not tolerate the maximum recommended dose of the drug, a gradual dose reduction is possible.

During the titration phase or after it, temporary worsening of CHF, arterial hypotension or bradycardia may occur. In this case, it is recommended first of all to adjust the doses of concomitant therapy drugs. It may also be necessary to temporarily reduce the dose of Concor ® Cor or discontinue it.

After stabilization of the patient's condition, the dose should be re-titrated or treatment should be continued.

Duration of treatment. Treatment with Concor ® Cor is usually long-term therapy.

Special patient groups

Impaired kidney or liver function. Mild or moderate hepatic or renal impairment usually does not require dose adjustment.

In case of severe renal dysfunction (creatinine Cl less than 20 ml/min) and in patients with severe liver disease, the maximum daily dose is 10 mg. Increasing the dose in such patients should be carried out with extreme caution.

Elderly patients. No dose adjustment is required.

Children. Since there is not enough data on the use of Concor ® Cor in children, it is not recommended to prescribe the drug to children under 18 years of age.

To date, there is insufficient data regarding the use of the drug Concor ® Cor in patients with CHF in combination with type 1 diabetes mellitus, severe renal and/or liver dysfunction, restrictive cardiomyopathy, congenital heart defects or heart valve disease with severe hemodynamic disturbances. Also, sufficient data have not yet been obtained regarding patients with CHF with myocardial infarction within the last 3 months.

Overdose

Symptoms: most often - AV blockade, severe bradycardia, marked decrease in blood pressure, bronchospasm, acute heart failure and hypoglycemia.

Sensitivity to a single high dose of bisoprolol varies greatly among individual patients and patients with CHF are likely to be highly sensitive.

Treatment: If an overdose occurs, first of all it is necessary to stop taking the drug and begin supportive symptomatic therapy.

With severe bradycardia: intravenous administration of atropine. If the effect is insufficient, a drug with a positive chronotropic effect can be administered with caution. Sometimes temporary placement of an artificial pacemaker may be necessary.

With a pronounced decrease in blood pressure: intravenous administration of plasma-substituting solutions and vasopressor drugs.

With AV block: patients should be closely monitored and treated with beta-agonists such as epinephrine. If necessary, install an artificial pacemaker.

In case of exacerbation of CHF: intravenous administration of diuretics, drugs with a positive inotropic effect, as well as vasodilators.

For bronchospasm: prescription of bronchodilators, incl. beta 2-adrenergic agonists and/or aminophylline.

For hypoglycemia: IV administration of dextrose (glucose).

special instructions

You should not interrupt treatment with Concor ® Cor abruptly and change the recommended dose without first consulting your doctor, because this may lead to a temporary deterioration in heart function. Treatment should not be interrupted suddenly, especially in patients with coronary artery disease. If discontinuation of treatment is necessary, the dose should be reduced gradually.

At the initial stages of treatment with Concor ® Cor, patients require constant monitoring.

The drug should be used with caution in the following cases: severe forms of COPD and non-severe forms of bronchial asthma; diabetes mellitus with significant fluctuations in blood glucose concentration: symptoms of a pronounced decrease in glucose concentration (hypoglycemia), such as tachycardia, palpitations or increased sweating, may be masked; strict diet; carrying out desensitizing therapy; AV blockade, first degree; Prinzmetal's angina; mild to moderate peripheral arterial circulatory disorders (increased symptoms may occur at the beginning of therapy); psoriasis (including history).

Respiratory system: for bronchial asthma or COPD, simultaneous use of bronchodilators is indicated. In patients with bronchial asthma, there may be an increase in airway resistance, which requires a higher dose of beta 2-adrenergic agonists. In patients with COPD, bisoprolol prescribed in combination therapy for the treatment of heart failure should be started at the lowest possible dose, and patients should be carefully monitored for the appearance of new symptoms (eg, shortness of breath, exercise intolerance, cough).

Allergic reactions: beta-blockers, including Concor ® Cor, may increase sensitivity to allergens and the severity of anaphylactic reactions due to weakening of adrenergic compensatory regulation under the influence of beta-blockers. Therapy with epinephrine (adrenaline) does not always give the expected therapeutic effect.

General anesthesia: When performing general anesthesia, the risk of beta-adrenergic receptor blockade should be taken into account. If it is necessary to discontinue therapy with Concor ® Cor before surgery, this should be done gradually and completed 48 hours before general anesthesia. The anesthesiologist should be warned that the patient is taking the drug Concor ® Cor.

Pheochromocytoma: in patients with an adrenal tumor (pheochromocytoma), the drug Concor ® Cor can only be prescribed while using alpha-blockers.

Hyperthyroidism: When treated with Concor ® Cor, symptoms of hyperfunction of the thyroid gland (hyperthyroidism) may be masked.

Influence on the ability to drive vehicles and complex mechanisms. The drug Concor ® Cor does not affect the ability to drive vehicles, according to the results of a study in patients with coronary artery disease. However, due to individual reactions, the ability to drive vehicles or operate technically complex mechanisms may be impaired. Particular attention should be paid to this at the beginning of treatment, after changing the dose, and also when consuming alcohol at the same time.

Release form

Film-coated tablets 2.5 mg.

Beta 1-adrenergic blocker selective

Active substance

Release form, composition and packaging

light yellow in color, heart-shaped, biconvex, with a notch on both sides.

Excipients: anhydrous calcium hydrogen phosphate - 132 mg, corn starch (fine powder) - 14.5 mg, anhydrous colloidal silicon dioxide - 1.5 mg, microcrystalline cellulose - 10 mg, crospovidone - 5.5 mg, magnesium stearate - 1.5 mg.

Film shell composition: hypromellose 2910/15 - 2.2 mg, macrogol 400 - 0.53 mg, dimethicone 100 - 0.11 mg, iron dye yellow oxide (E172) - 0.02 mg, titanium dioxide (E171) - 0.97 mg.

30 pcs. - blisters (3) - cardboard packs.

Film-coated tablets light orange in color, heart-shaped, biconvex, with a notch on both sides.

Excipients: anhydrous calcium hydrogen phosphate - 127.5 mg, corn starch (fine powder) - 14 mg, anhydrous colloidal silicon dioxide - 1.5 mg, microcrystalline cellulose - 10 mg, crospovidone - 5.5 mg, magnesium stearate - 1.5 mg.

Film shell composition: hypromellose 2910/15 - 2.2 mg, macrogol 400 - 0.53 mg, dimethicone 100 - 0.22 mg, iron dye yellow oxide (E172) - 0.12 mg, iron dye red oxide (E172) - 0.002 mg, titanium dioxide (E171) - 0.85 mg .

10 pieces. - blisters (3) - cardboard packs.
10 pieces. - blisters (5) - cardboard packs.
25 pcs. - blisters (2) - cardboard packs.
30 pcs. - blisters (1) - cardboard packs.

pharmachologic effect

A selective beta 1-blocker, without its own sympathomimetic activity, does not have a membrane-stabilizing effect.

It has only slight affinity for β 2 -adrenergic receptors of the smooth muscles of the bronchi and blood vessels, as well as for β 2 -adrenergic receptors involved in the regulation of metabolism. Therefore, bisoprolol generally does not affect airway resistance and metabolic processes in which β 2 -adrenergic receptors are involved.

The selective effect of the drug on β 1 -adrenergic receptors persists beyond the therapeutic range.

Bisoprolol does not have a pronounced negative inotropic effect.

The maximum effect of the drug is achieved 3-4 hours after oral administration. Even when bisoprolol is prescribed once a day, its therapeutic effect persists for 24 hours due to its 10-12 hour half-life from the blood. As a rule, the maximum reduction in blood pressure is achieved 2 weeks after the start of treatment.

Bisoprolol reduces the activity of the sympathoadrenal system by blocking β 1 -adrenergic receptors of the heart.

When administered once orally in patients with coronary artery disease without signs of chronic heart failure, bisoprolol reduces heart rate, reduces the stroke volume of the heart and, as a result, reduces the ejection fraction and myocardial oxygen demand. With long-term therapy, the initially elevated TPR decreases. A decrease in renin activity in blood plasma is considered as one of the components of the hypotensive effect.

Pharmacokinetics

Suction

Bisoprolol is almost completely (>90%) absorbed from the gastrointestinal tract. Its bioavailability due to the low degree of first-pass metabolism through the liver (at approximately 10%) is approximately 90% after oral administration. Food intake does not affect bioavailability. Bisoprolol exhibits linear kinetics, with plasma concentrations being proportional to the dose administered over a dose range of 5 to 20 mg. Cmax in blood plasma is reached after 2-3 hours.

Distribution

Bisoprolol is distributed quite widely. Vd is 3.5 l/kg. Plasma protein binding reaches approximately 30%.

Metabolism

Metabolized via the oxidative pathway without subsequent conjugation. All metabolites are polar (water-soluble) and are excreted by the kidneys. The main metabolites found in blood plasma and urine do not exhibit pharmacological activity. Data obtained from experiments with human liver microsomes in vitro show that bisoprolol is metabolized primarily by the CYP3A4 isoenzyme (about 95%), with the CYP2D6 isoenzyme playing only a minor role.

Removal

The clearance of bisoprolol is determined by the balance between excretion by the kidneys unchanged (about 50%) and metabolism in the liver (about 50%) to metabolites, which are also excreted by the kidneys. The total clearance is 15 l/h. T 1/2 is 10-12 hours.

There is no information on the pharmacokinetics of bisoprolol in patients with CHF and concurrent impairment of liver or kidney function.

Indications

Contraindications

- hypersensitivity to bisoprolol or any of the excipients;

- acute heart failure, chronic heart failure in the stage of decompensation, requiring inotropic therapy;

- cardiogenic shock;

— AV block II and III degrees, without pacemaker;

- sinoatrial block;

- severe bradycardia (HR< 60 уд./мин);

- severe arterial hypotension (systolic blood pressure< 100 мм рт.ст.);

- severe forms of bronchial asthma;

- severe disturbances of peripheral arterial circulation, Raynaud's syndrome;

- pheochromocytoma (without simultaneous use of alpha-blockers);

- metabolic acidosis;

- age under 18 years (insufficient data on effectiveness and safety).

With caution: carrying out desensitizing therapy, Prinzmetal's angina, hyperthyroidism, type I diabetes mellitus and diabetes mellitus with significant fluctuations in blood concentrations, first degree AV blockade, severe renal failure (creatinine clearance less than 20 ml/min), severe liver dysfunction, psoriasis , restrictive cardiomyopathy, congenital heart defects or heart valve disease with severe hemodynamic disturbances, CHF with myocardial infarction within the last 3 months, severe forms of COPD, strict diet.

Dosage

Tablets of the drug should be taken once a day with a small amount of liquid, in the morning before, during or after breakfast. The tablets should not be chewed or crushed into powder.

Arterial hypertension and stable angina

In all cases, the doctor selects the dosage regimen and dose individually for each patient, in particular, taking into account the heart rate and condition of the patient. Usually the initial dose is 5 mg of Concor once a day.

As a rule, the initial dose is 5 mg 1 time per day. If necessary, the dose can be increased to 10 mg 1 time per day. In the treatment of arterial hypertension and stable angina, the maximum recommended dose is 20 mg 1 time per day.

Chronic heart failure

The standard treatment regimen for chronic heart failure includes the use of ACE inhibitors or angiotensin II receptor antagonists (in case of intolerance to ACE inhibitors), beta-blockers, diuretics and, optionally, cardiac glycosides. Initiation of treatment for CHF with Concor requires a special titration phase and regular medical monitoring. The precondition for treatment with Concor is stable CHF without signs of exacerbation.

Treatment with Concor begins in accordance with the following titration scheme. Individual adaptation may be required depending on how well the patient tolerates the prescribed dose, i.e. the dose can only be increased if the previous dose was well tolerated.

To ensure an appropriate titration process, it is recommended to use bisoprolol in the dosage form of 2.5 mg tablets at the initial stages of treatment.

The recommended starting dose is 1.25 mg 1 time/day. Depending on individual tolerance, the dose should be gradually increased to 2.5 mg, 3.75 mg, 5 mg, 7.5 mg and 10 mg once a day. Each subsequent dose increase should be carried out at least 2 weeks later. If increasing the dose of the drug is poorly tolerated by the patient, a dose reduction may be possible.

During titration, regular monitoring of blood pressure, heart rate and the severity of symptoms of chronic heart failure is recommended. Worsening of the symptoms of chronic heart failure is possible from the first day of using the drug.

If the patient does not tolerate the maximum recommended dose of the drug, then a gradual dose reduction should be considered.

During the titration phase or after it, temporary worsening of CHF, arterial hypotension or bradycardia may occur. In this case, it is recommended, first of all, to adjust the doses of concomitant therapy drugs. It may also be necessary to temporarily reduce the dose of Concor or discontinue it. After stabilization of the patient's condition, the dose should be re-titrated or treatment should be continued.

Duration of treatment for all indications

Treatment with Concor is usually long-term.

Special patient groups

Impaired kidney or liver function

Mild or moderate hepatic or renal impairment usually does not require dose adjustment.

In case of severe renal impairment (creatinine clearance less than 20 ml/min) and in patients with severe liver disease, the maximum daily dose is 10 mg. Increasing the dose in such patients should be carried out with extreme caution.

Elderly patients

No dose adjustment is required.

Children

Because There is not enough data on the use of the drug Concor in children; it is not recommended to prescribe the drug to children and adolescents under the age of 18 years.

To date, there is insufficient data regarding the use of Concor in patients with chronic heart failure in combination with type 1 diabetes mellitus, severe renal and/or liver dysfunction, restrictive cardiomyopathy, congenital heart defects or heart valve disease with severe hemodynamic impairment. Also, sufficient data have not yet been obtained regarding patients with chronic heart failure with myocardial infarction within the last 3 months.

Side effects

The frequency of the adverse reactions listed below was determined according to the following: very often (≥1/10); often (≥ 1/100,<1/10); нечасто (≥ 1/1000, <1/100); редко (≥ 1/10 000, <1/1000); очень редко (< 1/10 000).

From the cardiovascular system: very often - bradycardia (in patients with chronic heart failure); often - worsening symptoms of chronic heart failure (in patients with chronic heart failure), a feeling of coldness or numbness in the extremities, a marked decrease in blood pressure (especially in patients with chronic heart failure); uncommon - impaired AV conduction, bradycardia (in patients with arterial hypertension or angina pectoris), worsening symptoms of chronic heart failure (in patients with arterial hypertension or angina pectoris), orthostatic hypotension.

From the side of the central nervous system: often - dizziness*, headache*; rarely - loss of consciousness.

From the mental side: infrequently - depression, insomnia; rarely - hallucinations, nightmares.

From the side of the organ of vision: rarely - decreased lacrimation (should be taken into account when wearing contact lenses); very rarely - conjunctivitis.

On the part of the hearing organ: rarely - hearing impairment.

From the respiratory system: infrequently - bronchospasm in patients with bronchial asthma or a history of airway obstruction; rarely - allergic rhinitis.

From the digestive system: often - nausea, vomiting, diarrhea, constipation; rarely - hepatitis.

From the laboratory parameters: rarely - an increase in the concentration of triglycerides and the activity of “liver” transaminases in the blood (aspartate aminotransferase (AST) and alanine aminotransferase (ALT).

From the musculoskeletal system: infrequently - muscle weakness, muscle cramps.

From the skin: rarely - hypersensitivity reactions, such as itching, rash, hyperemia of the skin; very rarely - alopecia. Beta blockers may worsen psoriasis or cause a psoriasis-like rash.

From the reproductive system: rarely - impaired potency.

General violations: often - asthenia (in patients with chronic heart failure), increased fatigue*; infrequently - asthenia (in patients with arterial hypertension or angina pectoris).

*In patients with arterial hypertension or angina pectoris, these symptoms especially often appear at the beginning of the course of treatment. Typically, these phenomena are mild and usually disappear within 1-2 weeks after the start of treatment.

Overdose

Symptoms: most often - AV block, severe bradycardia, marked decrease in blood pressure, bronchospasm, acute heart failure and hypoglycemia. Sensitivity to a single high dose of bisoprolol varies widely among individual patients and patients with CHF are likely to be highly sensitive.

Treatment: If an overdose occurs, first of all, it is necessary to stop taking the drug and begin supportive symptomatic therapy.

For severe bradycardia, intravenous administration of atropine. If the effect is insufficient, a drug with a positive chronotropic effect can be administered with caution. Sometimes temporary placement of an artificial pacemaker may be necessary.

With a pronounced decrease in blood pressure - intravenous administration of vasopressor drugs.

For AV block: Patients should be closely monitored and treated with beta-agonists such as epinephrine. If necessary, install an artificial pacemaker.

In case of exacerbation of chronic heart failure - intravenous administration of diuretics, drugs with a positive inotropic effect, as well as vasodilators.

For bronchospasm, prescribe bronchodilators, incl. beta 2-adrenergic agonists and/or aminophylline.

For hypoglycemia, intravenous administration of dextrose (glucose).

Drug interactions

The effectiveness and tolerability of bisoprolol may be affected by concomitant use of other medications. This interaction can also occur when two drugs are taken within a short period of time. The doctor must be informed about the use of other medications, even if they are taken without a doctor's prescription (i.e., over-the-counter drugs).

Treatment of chronic heart failure

Class I antiarrhythmic drugs (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone), when used simultaneously with bisoprolol, can reduce AV conduction and cardiac contractility.

Blockers of “slow” calcium channels such as verapamil and, to a lesser extent, diltiazem, when used simultaneously with bisoprolol, can lead to a decrease in myocardial contractility and impaired AV conduction. In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV block. Centrally acting antihypertensives (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to a decrease in heart rate and cardiac output, as well as vasodilation due to a decrease in central sympathetic tone. Abrupt withdrawal, especially before discontinuation of beta-blockers, may increase the risk of developing rebound hypertension.

Combinations requiring special caution

Treatment of arterial hypertension and angina pectoris

Class I antiarrhythmic drugs (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone), when used simultaneously with bisoprolol, can reduce AV conduction and myocardial contractility.

All indications for use of the drug Concor

BMCC dihydropyridine derivatives (for example, nifedipine, felodipine, amlodipine) when used simultaneously with bisoprolol may increase the risk of arterial hypotension. In patients with chronic heart failure, the risk of subsequent deterioration of cardiac contractile function cannot be excluded.

Class III antiarrhythmic drugs (for example, amiodarone), when used simultaneously with bisoprolol, may increase AV conduction disturbances.

The effect of beta-blockers for topical use (for example, eye drops for the treatment of glaucoma) may enhance the systemic effects of bisoprolol (lowering blood pressure, lowering heart rate).

Parasympathomimetics, when used simultaneously with bisoprolol, may increase AV conduction disturbances and increase the risk of developing bradycardia.

The hypoglycemic effect of insulin or oral hypoglycemic agents may be enhanced. Signs of hypoglycemia, in particular tachycardia, may be masked or suppressed. Such an interaction is more likely when using non-selective beta-blockers.

General anesthesia agents may increase the risk of cardiodepressive effects, leading to hypotension.

Cardiac glycosides, when used simultaneously with bisoprolol, can lead to an increase in impulse conduction time, and thus to the development of bradycardia.

NSAIDs can reduce the hypotensive effect of bisoprolol.

The simultaneous use of Concor with beta-agonists (for example, isoprenaline, dobutamine) may lead to a decrease in the effect of both drugs.

The combination of bisoprolol with adrenergic agonists that affect α- and β-adrenergic receptors (for example, norepinephrine, epinephrine) may enhance the vasoconstrictor effects of these drugs that occur with the participation of α-adrenergic receptors, leading to an increase in blood pressure. Such an interaction is more likely when using non-selective beta-blockers.

Antihypertensive drugs, as well as other drugs with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines) can enhance the hypotensive effect of bisoprolol.

Mefloquine, when used simultaneously with bisoprolol, can increase the risk of bradycardia.

MAO inhibitors (except MAO B inhibitors) may enhance the hypotensive effect of beta-blockers. Concomitant use may also lead to the development of a hypertensive crisis.

special instructions

Do not interrupt treatment with Concor abruptly or change the recommended dose without first consulting your doctor, because this may lead to a temporary deterioration in heart function.

Treatment should not be interrupted suddenly, especially in patients with coronary artery disease. If discontinuation of treatment is necessary, the dose should be reduced gradually.

During the initial stages of treatment with Concor, patients require constant monitoring.

The drug should be used with caution in the following cases:

Severe forms of COPD and non-severe forms of bronchial asthma;

Diabetes mellitus with significant fluctuations in blood glucose concentration: symptoms of a pronounced decrease in glucose concentration (hypoglycemia), such as tachycardia, palpitations or increased sweating, may be masked;

Strict diet;

Carrying out desensitizing therapy;

AV block of the first degree;

Prinzmetal's angina;

Mild to moderate peripheral arterial circulation disorders (increased symptoms may occur at the beginning of therapy);

Psoriasis (including history).

Respiratory system: for bronchial asthma or COPD, simultaneous use of bronchodilators is indicated. In patients with bronchial asthma, there may be an increase in airway resistance, which requires a higher dose of beta 2-adrenergic agonists. In patients with COPD, treatment with bisoprolol when prescribed in combination therapy for the treatment of heart failure should be started with the lowest possible dose, and patients should be carefully monitored for the appearance of new symptoms (for example, shortness of breath, exercise intolerance, cough).

Allergic reactions: beta-blockers, including Concor, may increase sensitivity to allergens and the severity of anaphylactic reactions due to a weakening of adrenergic compensatory regulation under their action. Therapy with epinephrine (adrenaline) does not always give the expected therapeutic effect.

General anesthesia: When performing general anesthesia, the risk of β-adrenergic receptor blockade should be taken into account. If it is necessary to discontinue therapy with Concor before surgery, this should be done gradually and completed 48 hours before general anesthesia. You should notify your anesthesiologist that you are taking Concor.

Pheochromocytoma: in patients with an adrenal tumor (pheochromocytoma), Concor can only be prescribed while using alpha-blockers.

Hyperthyroidism: When treated with Concor, the symptoms of hyperthyroidism may be masked.

Impact on the ability to drive vehicles and machinery

The drug Concor does not affect the ability to drive vehicles, according to the results of a study in patients with coronary artery disease. However, due to individual reactions, the ability to drive a car or work with technically complex mechanisms may be impaired. Particular attention should be paid to this at the beginning of treatment, after changing the dose, and also when consuming alcohol at the same time.

Pregnancy and lactation

During pregnancy, Concor should be recommended for use only if the benefit to the mother outweighs the risk of side effects in the fetus and/or child.

In general, beta blockers reduce blood flow to the placenta and may affect fetal development. Blood flow in the placenta and uterus should be monitored, as well as the growth and development of the unborn child should be monitored, and if adverse events occur in relation to pregnancy and/or the fetus, alternative methods of therapy should be taken.

The newborn should be carefully examined after birth. In the first 3 days of life, symptoms of bradycardia and hypoglycemia may occur.

There is no data on the excretion of bisoprolol into breast milk. Therefore, taking Concor is not recommended for women during breastfeeding. If taking the drug during lactation is necessary, breastfeeding should be discontinued.

For patients with severe liver dysfunction the maximum daily dose is 10 mg.

Use in old age

Elderly patients no dose adjustment is required.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

RUS-CIS/CONCO/0718/0049

Storage conditions and periods

The drug should be stored out of the reach of children at a temperature not exceeding 30 °C. Shelf life - 5 years.

Concor Cor (active ingredient - bisoprolol) is an original German beta-1 adrenergic blocker, used mainly for the treatment of chronic heart failure. The pharmacological group of drugs to which Concor Cor belongs is of particular importance to cardiologists. Suffice it to say that the Nobel Committee recognized its creation as the greatest breakthrough in the treatment of cardiovascular diseases since the discovery of digitalis preparations.

The use of beta-blockers in clinical practice has proven the correctness of the original idea of ​​their creators about the benefits that preventing catecholamines from entering the “body”, that is, the heart and blood vessels, can bring to heart patients. Today, beta-blockers are literally vital drugs: they have the most positive effect on the morbidity and mortality of cardiac patients, while being relatively safe in terms of the development of side effects. Their mechanism of action is based on the phenomenon of competitive antagonism with norepinephrine and adrenaline. Drugs of this class differ from each other in the selectivity of their action (the ability to block only beta-1 adrenergic receptors, which improves the safety profile of the drug) and the presence/absence of internal sympathomimetic activity, in other words, the ability to stimulate beta-adrenergic receptors simultaneously with blockade. Concor Cor is a selective beta-1 adrenergic blocker with no intrinsic sympathomimetic activity. It only has a small effect on beta-2 adrenergic receptors, so its effect on the smooth muscles of the bronchi and blood vessels, as well as on metabolic processes, is minimal.

The selective effect of concor core on beta-1 adrenergic receptors is maintained even if the therapeutic threshold is exceeded. Like beta-blockers, the drug has antiarrhythmic, antihypertensive and antianginal (anti-ischemic) effects. In patients suffering from coronary heart disease without symptoms of chronic heart failure, Concor Cor reduces the heart rate and systolic volume of the heart, which leads to a decrease in cardiac output and the heart's need for oxygen. With long-term use of the drug, the total peripheral vascular resistance normalizes.

Concor Cor is available in a single dosage form - tablets. Frequency and characteristics of administration - 1 time per day, washed down with a small amount of water. The optimal time to take it is in the morning on an empty stomach, during breakfast or after it. The condition for using Concor Cort is stable, without signs of exacerbation, chronic heart failure. For the purpose of its treatment, it is best to combine Concor Cor with angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, diuretics and, in some cases, cardiac glycosides. According to general recommendations, Concor Cor is started at 1.25 mg once a day. Depending on the patient’s body’s response to the drug, it is possible to gradually increase the dose (no more than once every 2 weeks) to the maximum recommended 10 mg.

Pharmacology

A selective beta 1-blocker, without its own sympathomimetic activity, does not have a membrane-stabilizing effect.

Reduces plasma renin activity, reduces myocardial oxygen demand, and reduces heart rate (at rest and during exercise). It has hypotensive, antiarrhythmic and antianginal effects. By blocking β 1-adrenergic receptors of the heart in low doses, it reduces the catecholamine-stimulated formation of cAMP from ATP, reduces the intracellular current of calcium ions, and has a negative chrono-, dromo-, bathmo- and inotropic effect (inhibits conductivity and excitability, slows down AV conduction). When increasing the dose above the therapeutic dose, it has a beta 2-adrenergic blocking effect.

At the beginning of using the drug, in the first 24 hours, the OPSS increases slightly (as a result of a reciprocal increase in the activity of α-adrenergic receptors), which returns to the original level after 1-3 days, and decreases with long-term administration.

The hypotensive effect is associated with a decrease in minute blood volume, sympathetic stimulation of peripheral vessels, a decrease in the activity of the renin-angiotensin system (of great importance for patients with initial hypersecretion of renin), restoration of sensitivity in response to a decrease in blood pressure and an effect on the central nervous system. In case of arterial hypertension, the effect occurs after 2-5 days, stable effect - after 1-2 months.

The antianginal effect is due to a decrease in myocardial oxygen demand as a result of a decrease in heart rate, a slight decrease in contractility, prolongation of diastole, and improved myocardial perfusion.

The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP content, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and a slowdown in AV conduction (mainly in the antegrade and, to a lesser extent, in the retrograde directions via the AV node) and along additional paths.

When used in average therapeutic doses, in contrast to non-selective beta-blockers, it has a less pronounced effect on organs containing β 2 -adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause retention of sodium ions in the body; the severity of the atherogenic effect does not differ from the effect of propranolol.

Pharmacokinetics

Suction

Bisoprolol is almost completely (>90%) absorbed from the gastrointestinal tract. Its bioavailability is approximately 85-90% after oral administration; food intake does not affect bioavailability. Bisoprolol exhibits linear kinetics, with plasma concentrations being proportional to the administered dose over a dose range of 5 to 20 mg. Cmax in blood plasma is reached after 2-3 hours.

Distribution

Bisoprolol is distributed quite widely. Vd is 3.5 l/kg. The binding to plasma proteins reaches approximately 35%; no uptake by blood cells is observed.

Metabolism

Metabolized mainly through the oxidative pathway without subsequent conjugation; there is insignificant “first pass” metabolization through the liver (at a level of approximately 10-15%). All metabolites have strong polarity. The main metabolites found in blood plasma and urine do not exhibit pharmacological activity. Data obtained from in vitro experiments with human liver microsomes indicate that bisoprolol is metabolized primarily by CYP3A4 (about 95%), with CYP2D6 playing only a minor role.

Removal

The clearance of bisoprolol is determined by the balance between its excretion through the kidneys as unchanged substance (about 50%) and oxidation in the liver (about 50%) to metabolites, which are then also excreted by the kidneys. The total clearance is 15.6 ± 3.2 l/h, with renal clearance being 9.6 ± 1.6 l/h. T 1/2 is 10-12 hours.

Release form

White, film-coated tablets, heart-shaped, biconvex, scored on both sides.

Excipients: calcium hydrogen phosphate, anhydrous - 134.0 mg, corn starch, fine powder - 15.0 mg, colloidal silicon dioxide, anhydrous - 1.5 mg, microcrystalline cellulose - 10.0 mg, crospovidone - 5.5 mg, magnesium stearate - 1.5 mg.

Film shell composition: hypromellose 2910/15 - 2.20 mg, macrogol 400 - 0.53 mg, dimethicone 100 - 0.11 mg, titanium oxide (E171) - 1.22 mg.

10 pieces. - blisters (3) - cardboard packs.
14 pcs. - blisters (1) - cardboard packs.
25 pcs. - blisters (2) - cardboard packs.
30 pcs. - blisters (1) - cardboard packs.

Dosage

The tablets should be taken orally with a small amount of liquid in the morning before, during or after breakfast. The tablets should not be chewed or crushed into powder.

Initiation of treatment for chronic heart failure with Concor Cor requires a special titration phase and regular medical supervision.

Prerequisites for treatment with Concor Cor

Chronic heart failure without signs of exacerbation in the previous 6 weeks;

Almost unchanged basic therapy in the previous 2 weeks;

Treatment with optimal doses of ACE inhibitors (or other vasodilators in case of intolerance to ACE inhibitors), diuretics and, optionally, cardiac glycosides.

Treatment of chronic heart failure with Concor Cor begins in accordance with the following titration scheme. Individual adaptation may be required depending on how well the patient tolerates the prescribed dose, i.e. the dose can only be increased if the previous dose was well tolerated.

*To ensure the above dosage regimen, it is recommended to use the drug Concor in subsequent stages of treatment.

After starting treatment with the drug at a dose of 1.25 mg (1/2 tablet of Concor Cor), the patient should be observed for 4 hours (monitoring heart rate, blood pressure, conduction disturbances, signs of worsening heart failure).

During or after the titration phase, temporary worsening of heart failure, fluid retention, hypotension, or bradycardia may occur. In this case, it is recommended to pay attention to the selection of the dosage of concomitant basic therapy (optimize the dose of a diuretic and/or ACE inhibitor) before reducing the dosage of Concor Cor. After stabilization of the patient's condition, re-titration should be carried out, or treatment should be continued.

Treatment with Concor Cor is usually long-term. If necessary, treatment can be interrupted and resumed subject to certain rules. Treatment should not be interrupted suddenly, especially in patients with coronary artery disease. If discontinuation of treatment is necessary, the dosage of the drug should be reduced gradually.

In case of severe renal dysfunction (KR<20 мл/мин) и у пациентов с тяжелыми заболеваниями печени максимальная суточная доза препарата составляет 10 мг.

Mild or moderate hepatic or renal impairment usually does not require dose adjustment.

When using the drug in elderly patients, no dose adjustment is required.

Overdose

Symptoms: arrhythmia, ventricular extrasystole, severe bradycardia, AV block, marked decrease in blood pressure, acute heart failure, hypoglycemia, acrocyanosis, difficulty breathing, bronchospasm, dizziness, fainting, convulsions.

Treatment: gastric lavage, administration of adsorbent drugs, symptomatic therapy. If AV blockade has developed, 1-2 mg of atropine, epinephrine should be administered intravenously or a temporary pacemaker should be installed. For ventricular extrasystole - lidocaine (class I A drugs are not used). If there is a pronounced decrease in blood pressure, the patient should be in the Trendelenburg position; if there are no signs of pulmonary edema, IV plasma-substituting solutions; if they are ineffective, epinephrine, dopamine, dobutamine (to maintain the chronotropic and inotropic effects and eliminate the pronounced decrease in blood pressure). For heart failure - cardiac glycosides, diuretics, glucagon. For convulsions - intravenous diazepam. For bronchospasm - inhaled beta 2-adrenergic stimulants.

Interaction

The effectiveness and tolerability of drugs may be affected by concomitant use of other drugs. This interaction can also occur when two drugs are taken within a short period of time. The doctor must be informed about the use of other medications, even if used without a prescription.

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

Phenytoin, when administered intravenously, and drugs for inhalation general anesthesia (hydrocarbon derivatives) increase the severity of the cardiodepressive effect and the likelihood of a decrease in blood pressure.

The effectiveness of insulin and oral hypoglycemic drugs may change during treatment with bisoprolol (masks the symptoms of developing hypoglycemia: tachycardia, increased blood pressure).

The clearance of lidocaine and xanthines (except diphylline) may be reduced due to a possible increase in their concentration in the blood plasma, especially in patients with an initially increased clearance of theophylline under the influence of smoking.

NSAIDs, corticosteroids and estrogens weaken the hypotensive effect of bisoprolol (retention of sodium ions, blockade of prostaglandin synthesis by the kidneys).

Cardiac glycosides, methyldopa, reserpine and guanfacine, slow calcium channel blockers (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or worsening bradycardia, AV block, cardiac arrest and heart failure.

Nifedipine can lead to a significant decrease in blood pressure.

Diuretics, clonidine, sympatholytics, hydralazine and other antihypertensive drugs can lead to an excessive decrease in blood pressure.

The effect of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins may be prolonged during treatment with bisoprolol.

Tricyclic and tetracyclic antidepressants, antipsychotics (neuroleptics), ethanol, sedatives and hypnotics increase CNS depression.

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

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

Sulfasalazine increases the concentration of bisoprolol in the blood plasma.

Rifampicin shortens the half-life of bisoprolol.

Side effects

The frequency of adverse reactions listed below was determined according to the following gradations: very often (≥10%); often (>1%,<10%), нечасто (>0.1%, <1%), редко (>0.01%, <0.1%); очень редко (≤0.01%, включая отдельные сообщения).

From the cardiovascular system: very often - decreased heart rate (bradycardia, especially in patients with chronic heart failure); often - arterial hypotension (especially in patients with chronic heart failure), manifestation of vasospasm (increased peripheral circulatory disorders, feeling of cold in the extremities (paresthesia); sometimes - impaired AV conduction, orthostatic arterial hypotension, decompensation of heart failure with the development of peripheral edema.

From the side of the central nervous system: sometimes - dizziness, headache, asthenia, increased fatigue, sleep disturbances, depression; rarely - hallucinations, nightmares, convulsions. Usually these phenomena are mild and disappear, as a rule, within 1-2 weeks after the start of treatment.

On the part of the organ of vision: rarely - blurred vision, decreased tear production (should be taken into account when wearing contact lenses); very rarely - conjunctivitis.

From the respiratory system: sometimes - bronchospasm in patients with bronchial asthma or obstructive airway diseases; rarely - allergic rhinitis.

From the digestive system: often - nausea, vomiting, diarrhea, constipation, dry oral mucosa; rarely - hepatitis, increased levels of liver enzymes in the blood (AST, ALT).

From the musculoskeletal system: sometimes - muscle weakness, cramps in the calf muscles, arthralgia.

From the reproductive system: very rarely - potency disorders.

Laboratory indicators: rarely - increased levels of triglycerides in the blood; in some cases - thrombocytopenia, agranulocytosis.

Allergic reactions: rarely - itching, redness of the skin, rash.

Dermatological reactions: rarely - sweating; very rarely - alopecia. Beta blockers can aggravate psoriasis.

Indications

Chronic heart failure.

Contraindications

• acute heart failure;
• chronic heart failure in the stage of decompensation;
• shock caused by impaired cardiac function (cardiogenic shock);
• collapse;
• AV block II and III degrees, without pacemaker;
• SSSU;
• sinoatrial block;
• severe bradycardia (HR<50 уд./мин.);
• Prinzmetal's angina;
• pronounced decrease in blood pressure (systolic blood pressure<90 мм рт.
  Art.);
• history of severe forms of bronchial asthma and COPD;
• late stages of peripheral circulatory disorders, Raynaud's disease;
• pheochromocytoma (without simultaneous use of alpha-blockers);
• metabolic acidosis;
• simultaneous use of MAO inhibitors (with the exception of
  MAO type B inhibitors);
• children and adolescents under 18 years of age (efficacy and safety have not been established);
• hypersensitivity to bisoprolol or any of the components and to other beta-blockers.

The drug should be used with caution in cases of liver failure, chronic renal failure, myasthenia gravis, thyrotoxicosis, diabetes mellitus, AV blockade of the first degree, depression (including a history), psoriasis, and in elderly patients.

Features of application

Use during pregnancy and breastfeeding

The use of Concor Cor during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus.

Beta blockers reduce blood flow to the placenta and may affect fetal development. Blood flow in the placenta and uterus should be closely monitored, as well as the growth and development of the unborn child, and in case of dangerous manifestations in relation to pregnancy or the fetus, alternative therapeutic measures should be taken. The newborn should be carefully examined after birth. In the first 3 days of life, symptoms of decreased blood glucose and heart rate may occur.

There is no data on the excretion of bisoprolol in breast milk or the safety of bisoprolol in infants. If it is necessary to use the drug during lactation, the issue of stopping breastfeeding should be decided.

Use for liver dysfunction

Use for renal impairment

special instructions

The patient should not abruptly interrupt treatment or change the recommended dose without first consulting a doctor, as this may lead to a temporary deterioration in heart function. Treatment should not be interrupted suddenly, especially in patients with coronary artery disease. If discontinuation of treatment is necessary, the dose should be reduced gradually.

Monitoring the condition of patients taking Concor Cor should include measuring heart rate and blood pressure (at the beginning of treatment - daily, then once every 3-4 months), conducting an ECG, determining blood glucose in patients with diabetes (once every 4-5 months). months). In elderly patients, it is recommended to monitor renal function (once every 4-5 months).

The patient should be trained in the method of calculating heart rate and instructed about the need for medical consultation in case of heart rate<50 уд./мин.

In approximately 20% of patients with angina, beta blockers are ineffective. Main causes: severe coronary atherosclerosis with a low ischemic threshold (HR<100 уд./мин) и повышенный конечный диастолический объем левого желудочка, нарушающий субэндокардиальный кровоток.

Beta blockers are less effective in smokers.

Patients who use contact lenses should take into account that during treatment with the drug, the production of tear fluid may decrease.

When using the drug Concor Cor in patients with pheochromocytoma, there is a risk of developing paradoxical arterial hypertension (if effective alpha-blockade is not previously achieved).

In case of thyrotoxicosis, Concor Cor can mask certain clinical signs of thyrotoxicosis (for example, tachycardia). Abrupt discontinuation of the drug in patients with thyrotoxicosis is contraindicated as it can increase symptoms.

In diabetes mellitus, the use of the drug may lead to masking of tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, Concor Cor practically does not increase insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentrations to normal levels.

When using clonidine simultaneously, its use can be discontinued only a few days after discontinuation of the drug Concor Cor.

It is possible that the severity of the hypersensitivity reaction may increase and there will be no effect from usual doses of epinephrine against the background of a burdened allergic history.

If planned surgical treatment is necessary, the drug should be discontinued 48 hours before general anesthesia. If the patient took the drug before surgery, he should select a drug for general anesthesia with minimal negative inotropic effects.

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

Drugs that deplete catecholamine stores (including reserpine) may enhance the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision to detect a significant decrease in blood pressure or bradycardia.

Patients with bronchospastic diseases can be prescribed cardioselective blockers in case of intolerance and/or ineffectiveness of other antihypertensive drugs. If the dose of Concor Cor is exceeded, there is a risk of developing bronchospasm.

If increasing bradycardia (HR) is detected in elderly patients<50 уд./мин), выраженного снижения АД (систолическое АД <100 мм рт.ст.), AV-блокады, необходимо уменьшить дозу или прекратить лечение.

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

The drug should be discontinued before testing the content of catecholamines, normetanephrine, vanillinmandelic acid, and antinuclear antibody titers in the blood and urine.

Impact on the ability to drive vehicles and operate machinery

Bisoprolol does not affect the ability to drive a car in a study of patients with coronary artery disease. However, due to individual reactions, the ability to drive a car or work with technically complex mechanisms may be impaired. Particular attention should be paid to this at the beginning of treatment, after changing the dose, and also when consuming alcohol at the same time.

Both drugs belong to the pharmacological group of medications that block the functionality of adrenergic receptors, reducing their activity. Most patients consider Concor and Concor Cor to be analogues, since their composition is based on the same substance - bisoprolol. It is recommended to use the drug for:

• high blood pressure (hypertension);
• angina pectoris (heart disease accompanied by pain in the central part of the chest);
• congestive type of heart failure;
• ischemia (decreased blood supply to organs due to reduced blood flow).

But at the same time, there is still a difference between the two drugs and it is unacceptable to prescribe one of them independently, without consulting a doctor.

The characteristic difference between the drugs Concor and Concor Cor

Both names are well known to people with heart pathologies, but few people pay attention to the differences in the dosage of the adrenergic blocker bisoprolol fumarate in the medications themselves. Concor Cor, unlike Concor, has a smaller amount of the main substance. If in the first case we are talking about 2.5 mg of bisoprolol, then in the second it will be 5 or 10 mg.

There is also an external difference between the tablets made in the shape of a heart. The fact that the medication contains 10 mg of an adrenergic blocker is indicated by its yellow-orange color. Since the composition of both drugs is identical, they can be distinguished by:

• packaging design;
• the dosage indicated on the front side;
• The Concor format is available in blisters of 10 tablets, and the medication with increased capacity of bisoprolol is available in packages of 30, 50 or 90 tablets;
• cost (the higher the dosage of the adrenergic blocker, the more expensive it will cost to purchase the drug itself).

If we take into account the difference in indications for use, then Concor with an increased dosage of the main substance is suitable for therapy:

• hypertension (arterial type hypertension);
• angina pectoris (angina pectoris);
• coronary heart disease.

It is the increased amount of bisoprolol that makes it possible to more effectively relieve (interrupt an attack of the disease) painful symptoms of cardiac pathologies without causing additional harm to the body. But it is extremely important to remember that the drug is selected by the doctor individually for each patient.

Concor Cor is considered more effective in the treatment of heart failure. It is necessary to start the course with 1.25 mg and only with the permission of the doctor the dose can be gradually increased. A high-dose drug can be dangerous in conditions such as chronic heart failure. In the fight against hypertension and ischemia, Concor Cor can be prescribed in combination with other drugs that affect the functionality of the heart.

Regardless of the dosage level of the adrenergic blocker, the drug is extremely dangerous for patients with heart failure at the stage of decompensation. It is prohibited for minors to take it, and it is also allowed to be used by pregnant women upon obtaining permission from a doctor (if there is no alternative to preserving the health of the expectant mother). In the latter case, maximum caution is determined by the ability of adrenergic blockers to reduce blood flow to the placenta, thereby provoking defects in the development and growth of the fetus.

It is recommended to take both drugs in the morning with a glass of clean water. The effect of the tablet lasts 24 hours, so the next dose can only be the next morning. Dosage increases are carried out under the exclusive supervision of the attending physician. The specialist also determines the duration of the course of taking the drug.

Having figured out how Concor differs from Concor Cor, it makes no sense to choose which drug is better or worse, because everything depends on the characteristics of the disease and if Concor Cor is recommended for use for hypertension, then for ischemia it can only worsen existing pathologies of heart disease.

Medicine Concor Cor and its features

According to the pharmacological group, the medicine belongs to adrenoblockers and is available in the form of tablets. The medication contains:

1. Bisoprolol fumarate (2.5 or 5 mg).
2. Colloidal silicon dioxide.
3. Crospovidone.
4. Magnesium stearate.
5. Corn starch.
6. Macrogol 400.
7. Dimethicone 100.
8. Calcium hydrophosphate.
9. Microcrystalline cellulose.

One package of the drug contains 30 tablets. After administration, the effect develops over several hours and lasts a day. The main nature of the effect is hypotensive, due to a decrease in cardiac output. Due to a decrease in heart rate, the myocardial oxygen demand decreases, and a decrease in blood pressure levels is also observed. Taking the drug for chronic heart failure can alleviate the course of the disease.

Indications and contraindications for the use of the drug Concor Cor

• arterial hypertension;
• angina pectoris;
• chronic heart failure.

Medicines are prohibited for use if:

• sick sinus syndrome (SSNS);
• state of shock;
• sinoatrial blockade with severe symptoms;
• the patient's tendency to exhibit bronchospasms (bronchial asthma);
• impaired peripheral circulation (late stages of disease development);
• psoriasis (including in the patient’s history and in his close circle);
• acute form of heart failure;
• simultaneous use of monoamine oxidase inhibitors (biological active substances).

Concor Cora should not be used if there is a low heart rate (50–60 beats per minute) or arterial hypotension (blood pressure is no higher than 90–100 mm Hg).

Instructions for use of the drug

The recommended dosage of the drug for initial use is 1.25 mg. It must be used in the morning with a glass of clean water. After a week, the dosage may be increased to 2.5 mg per dose if the patient does not experience any worsening of the condition and the drug is effective. From the beginning of the third week, you can switch to a dosage of 3.75 mg per daily dose. With the permission of the doctor, in the period from the fourth to the eighth week of therapy, the dosage of the drug can be set at 5 mg, and from the eighth to the twelfth week of the course - 7.5 mg. The maximum permissible dosage is 10 mg per day.

After the initial dose of the drug, a patient with chronic heart failure should be examined within the first four hours of exposure to the drug. Research concerns:

• blood pressure and heart rate measurements;
• possible disturbances in vascular conductivity;
• potential deterioration of the condition and aggravation of heart pathology.

The tablets themselves must be taken whole, without chewing. The drug is taken on an empty stomach or during the first meal. Sudden termination of the therapeutic course is dangerous due to serious complications. Its duration, as well as the dosage, is determined solely by the doctor. This also applies to the treatment of heart diseases during pregnancy.

Possible adverse reactions to taking the drug

Taking the drug may be accompanied by a number of side effects. First of all, this concerns:

• increased feeling of fatigue;
• dizziness and severe headaches;
• sleep disruptions;
• depression, hallucinations (occasionally);
• blurred vision and decreased tear production, which is dangerous when using contact lenses;
• bradycardia;
• dyspnea;
• diarrhea;
• manifestation of an allergic rash;
• muscle weakness.

The drug is quite serious and its use must be monitored by a doctor, because the dosage and duration of the course of treatment are prescribed individually in each individual case.

Medicine Concor and features of its use

The drug is available in the form of tablets with a special film coating. In addition to the main active ingredient bisoprolol fumarate in a dosage of 5 mg or 10 mg, the composition contains magnesium stearate, crospovidone, etc.

According to its pharmacological properties, the drug does not affect the performance of the respiratory system and the functioning of metabolic systems. The drug also does not have a negative inotropic effect. The drug begins to work fully within a four-hour period after taking the tablet and remains effective throughout the day. Maximum effectiveness from taking the drug can be observed after completing a two-week course of daily morning medication.

Indications for use of the drug and contraindications

The use of the product is carried out under the careful supervision of a physician. It is recommended for arterial hypertension (high blood pressure), coronary heart disease (angina), as well as for chronic heart failure when taken in combination with diuretics or glycosides.

The tablets must be taken entirely with water, without chewing. The maximum effect is possible only when using the drug in the morning on an empty stomach or during the first breakfast. It is unacceptable to use it more than once a day.

Treatment is usually carried out under the supervision of a doctor and with a gradual increase in the daily dose. Initially, 5 mg of bisoprolol is used. At the same time, treatment of non-severe forms of arterial hypertension can be carried out at a dosage of 2.5 mg (half a tablet at a time). To obtain greater effect, the daily dose can be increased to 10 mg. Taking the drug more than 10 mg per day is an exception and is allowed only in the absence of any other alternative treatments.

The dosage of the drug does not depend on the age of the patient, while it is not allowed in pediatrics (for the treatment of children), and also requires maximum seriousness when treating women during pregnancy.

• The medicine is contraindicated for use when:
• acute form of heart failure;
• existing cardiogenic shock;
• sick sinus syndrome;
• bradycardia of a symptomatic nature;
• arterial hypotension (low blood pressure);
• Raynaud's disease.

Due to the many risks of taking an adrenergic blocker, self-medication with this drug is not allowed. After the first dose of medication, the patient must be re-examined within the first four hours of exposure to the pill.

Possible adverse reactions of the body to taking the drug Concor:

• use for the treatment of angina pectoris and chronic heart failure may be accompanied by:
• manifestation of bradycardia;
• dizziness;
• increasing headaches;
• decreased tear production;
• conjunctivitis;
• hearing impairment;
• a manifestation of general weakness.

Numerous disorders in the functioning of organs can only be determined after laboratory analysis and research, which is why the patient must remain under the supervision of a doctor who would monitor his condition and adjust not only the dosage of the drug, but also the duration of the course itself.

Description and instructions for Concor Cor tab p.o 2.5 mg No. 30

Instructions for use
Concor Cor

Dosage forms
tablets 2.5 mg

Synonyms
Aritel
Aritel Kor
Bidop
Biol
Biprol
Bisogamma
Bisoprolol
Concor
Cordinorm
Coronal
Niperten

Group
Beta1-blockers (cardioselective)

International nonproprietary name
Bisoprolol

Compound
Active substance: bisoprolol hemifumarate (bisoprolol fumarate (2:1)) - 2.5 mg.

Manufacturers
Merck KGaA (Germany)

pharmachologic effect
Pharmacodynamics. A selective beta1 adrenergic blocker, without its own sympathomimetic activity, does not have a membrane-stabilizing effect. It has only slight affinity for beta2-adrenergic receptors of the smooth muscles of the bronchi and blood vessels, as well as for beta2-adrenergic receptors involved in the regulation of metabolism. Therefore, bisoprolol generally does not affect airway resistance and metabolic processes in which beta2-adrenoreceptors are involved. The selective effect of the drug on beta1-adrenergic receptors persists beyond the therapeutic range. When used once in patients with coronary heart disease (CHD) without signs of chronic heart failure (CHF), bisoprolol reduces the heart rate (HR), stroke volume of the heart and, as a result, reduces the ejection fraction and myocardial oxygen demand. With long-term therapy, the initially increased total peripheral vascular resistance (TPVR) decreases. Pharmacokinetics. Suction. Bisoprolol is almost completely (more than 90%) absorbed from the gastrointestinal tract. Its bioavailability due to negligible first-pass metabolism through the liver (at approximately 10%) is approximately 90% after oral administration. Food intake does not affect bioavailability. Bisoprolol exhibits linear kinetics, with its plasma concentrations being proportional to the dose taken in the range from 5 to 20 mg. The maximum concentration in blood plasma is achieved after 2-3 hours. Distribution. Bisoprolol is distributed quite widely. The volume of distribution is 3.5 l/kg. The binding to plasma proteins reaches approximately 30%. Metabolism. Metabolized via the oxidative pathway without subsequent conjugation. All metabolites are polar (water-soluble) and are excreted by the kidneys. The main metabolites found in blood plasma and urine do not exhibit pharmacological activity. Data obtained from in vitro experiments with human liver microsomes indicate that bisoprolol is metabolized primarily by the CYP3A4 isoenzyme (about 95%), with the CYP2D6 isoenzyme playing only a minor role. Excretion. The clearance of bisoprolol is determined by the balance between excretion by the kidneys unchanged (about 50%) and metabolism in the liver (about 50%) to metabolites, which are then also excreted by the kidneys. The total clearance is 15 l/hour. The half-life is 10-12 hours. There is no information on the pharmacokinetics of bisoprolol in patients with CHF and concurrent impairment of liver or kidney function.

Side effect
Central nervous system. Common: dizziness, headache; rarely: loss of consciousness. General violations. Often: asthenia, increased fatigue. Mental disorders. Uncommon: depression, insomnia; rarely: hallucinations, nightmares. From the side of the organ of vision. Rarely: decreased lacrimation (should be taken into account when wearing contact lenses); very rare: conjunctivitis. From the side of the hearing organ. Rarely: hearing impairment. From the cardiovascular system. Very common: bradycardia; often: worsening symptoms of CHF, feelings of coldness or numbness in the extremities, marked decrease in blood pressure; uncommon: AV conduction disturbance, orthostatic hypotension. From the respiratory system. Uncommon: bronchospasm in patients with a history of bronchial asthma or airway obstruction; rarely: allergic rhinitis. From the digestive tract. Common: nausea, vomiting, diarrhea, constipation; rarely: hepatitis. From the musculoskeletal system. Uncommon: muscle weakness, muscle cramps. From the side of the skin. Rarely: hypersensitivity reactions, such as itching, rash, hyperemia of the skin; very rarely: alopecia. Beta blockers may worsen psoriasis symptoms or cause a psoriasis-like rash. From the reproductive system. Rarely: potency disorders. Laboratory indicators. Rarely: increased concentration of triglycerides and activity of “liver” transaminases in the blood (aspartate aminotransferase (AST), alanine aminotransferase (ALT)).

Indications for use
Chronic heart failure.

Contraindications
Hypersensitivity to bisoprolol or to any of the excipients; acute heart failure, chronic heart failure in the stage of decompensation, requiring inotropic therapy; cardiogenic shock; atrioventricular (AV) block II and III degrees, without a pacemaker; sick sinus syndrome; sinoatrial blockade, severe bradycardia (heart rate less than 60 beats/min); severe arterial hypotension (systolic blood pressure less than 100 mm Hg); severe forms of bronchial asthma or chronic obstructive pulmonary disease; severe peripheral arterial circulation disorders or Raynaud's syndrome; pheochromocytoma (without simultaneous use of alpha-blockers); metabolic acidosis; age under 18 years (insufficient data on effectiveness and safety in this age group).

Directions for use and dosage
The tablets should be taken once a day with a small amount of liquid in the morning before, during or after breakfast. The tablets should not be chewed or crushed into powder. The standard treatment regimen for CHF includes the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists (in case of intolerance to ACE inhibitors), beta-blockers, diuretics and, optionally, cardiac glycosides. Initiation of treatment for CHF with the drug requires a special titration phase and regular medical supervision. The precondition for treatment with the drug is stable chronic heart failure without signs of exacerbation. Treatment of CHF with the drug begins in accordance with the following titration scheme. Individual adaptation may be required depending on how well the patient tolerates the prescribed dose, i.e. the dose can only be increased if the previous dose was well tolerated. The recommended starting dose is 1.25 mg once daily. Depending on individual tolerance, the dose should be gradually increased to 2.5 mg, 3.75 mg, 5 mg, 7.5 mg and 10 mg once a day. Each subsequent dose increase should be carried out at least two weeks later. If increasing the dose of the drug is poorly tolerated by the patient, a dose reduction may be possible. The maximum recommended dose for CHF is 10 mg of the drug once a day. During titration, regular monitoring of blood pressure, heart rate and the severity of CHF symptoms is recommended. Worsening of the symptoms of CHF is possible from the first day of using the drug. If the patient does not tolerate the maximum recommended dose of the drug, a gradual dose reduction is possible. During the titration phase or after it, temporary worsening of CHF, arterial hypotension or bradycardia may occur. In this case, it is recommended, first of all, to adjust the doses of concomitant therapy drugs. It may also be necessary to temporarily reduce the dose of the drug or discontinue it. After stabilization of the patient's condition, the dose should be re-titrated or treatment should be continued. Treatment with the drug is usually long-term therapy. Special groups of patients. Impaired kidney or liver function. Mild or moderate hepatic or renal impairment usually does not require dose adjustment. In case of severe renal dysfunction (creatinine clearance less than 20 ml/min.) and in patients with severe liver diseases, the maximum daily dose is 10 mg. Increasing the dose in such patients should be carried out with extreme caution. Elderly patients. No dose adjustment is required. Children. Since there is not enough data on the use of the drug in children, it is not recommended to prescribe the drug to children under 18 years of age. To date, there is insufficient data regarding the use of the drug in patients with CHF in combination with type 1 diabetes mellitus, severe renal and/or liver dysfunction, restrictive cardiomyopathy, congenital heart defects or heart valve disease with severe hemodynamic disturbances. Also, sufficient data have not yet been obtained regarding patients with CHF with myocardial infarction within the last 3 months.

Overdose
Symptoms The most common symptoms of overdose: AV block, severe bradycardia, marked decrease in blood pressure, bronchospasm, acute heart failure and hypoglycemia. Sensitivity to a single high dose of bisoprolol varies widely among individual patients and patients with CHF are likely to be highly sensitive. Treatment. If an overdose occurs, first of all, it is necessary to stop taking the drug and begin supportive symptomatic therapy. For severe bradycardia: intravenous administration of atropine. If the effect is insufficient, a drug with a positive chronotropic effect can be administered with caution. Sometimes temporary placement of an artificial pacemaker may be necessary. With a pronounced decrease in blood pressure: intravenous administration of plasma-substituting solutions and vasopressor drugs. For AV block: Patients should be closely monitored and treated with beta-agonists such as epinephrine. If necessary, install an artificial pacemaker. In case of exacerbation of CHF: intravenous administration of diuretics, drugs with a positive inotropic effect, as well as vasodilators. For bronchospasm: prescribing bronchodilators, including beta2-adrenergic agonists and/or aminophylline. For hypoglycemia: intravenous administration of dextrose (glucose).

Interaction
The effectiveness and tolerability of bisoprolol may be affected by concomitant use of other medications. This interaction can also occur when two drugs are taken within a short period of time. The doctor must be informed about taking other medications, even if taken without a doctor's prescription (i.e., over-the-counter drugs). Combinations not recommended. Class I antiarrhythmic drugs (for example, quinidine, disopyramide, lidocaine, phenytoin; flecainide, propafenone), when used simultaneously with bisoprolol, can reduce AV conduction and cardiac contractility. Blockers of “slow” calcium channels (SCBC) such as verapamil and, to a lesser extent, diltiazem, when used simultaneously with bisoprolol, can lead to a decrease in myocardial contractility and impaired AV conduction. In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV block. Centrally acting antihypertensives (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to a decrease in heart rate and cardiac output, as well as vasodilation due to a decrease in central sympathetic tone. Abrupt withdrawal, especially before discontinuation of beta-blockers, may increase the risk of developing “rebound” arterial hypertension. Combinations requiring special care. BMCC dihydropyridine derivatives (for example, nifedipine, felodipine, amlodipine) when used simultaneously with bisoprolol may increase the risk of arterial hypotension. In patients with CHF, the risk of subsequent deterioration in cardiac contractility cannot be excluded. Class III antiarrhythmic drugs (eg, amiodarone) may worsen AV conduction disturbances. The effect of beta-blockers for topical use (for example, eye drops for the treatment of glaucoma) may enhance the systemic effects of bisoprolol (lowering blood pressure, lowering heart rate). Parasympathomimetics, when used simultaneously with bisoprolol, may increase AV conduction disturbances and increase the risk of developing bradycardia. The hypoglycemic effect of insulin or oral hypoglycemic agents may be enhanced. Signs of hypoglycemia - in particular tachycardia - may be masked or suppressed. Such interactions are more likely when using non-selective beta-blockers. General anesthesia agents may increase the risk of cardiodepressive effects, leading to hypotension. Cardiac glycosides, when used simultaneously with bisoprolol, can lead to an increase in impulse conduction time, and thus to the development of bradycardia. Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the hypotensive effect of bisoprolol. Concomitant use of the drug with beta-agonists (for example, isoprenaline, dobutamine) may lead to a decrease in the effect of both drugs. The combination of bisoprolol with adrenergic agonists that affect beta and alpha adrenergic receptors (for example, norepinephrine, epinephrine) may enhance the vasoconstrictor effects of these drugs that occur with the participation of alpha adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely when using non-selective beta-blockers. Antihypertensive drugs, as well as other drugs with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines) may enhance the hypotensive effect of bisoprolol. Mefloquine, when used simultaneously with bisoprolol, may increase the risk of bradycardia. MAO inhibitors (except MAO B inhibitors) may enhance the hypotensive effect of beta-blockers. Concomitant use may also lead to the development of a hypertensive crisis.

special instructions
With caution: carrying out desensitizing therapy, Prinzmetal's angina, hyperthyroidism, type 1 diabetes mellitus and diabetes mellitus with significant fluctuations in blood glucose concentration, 1st degree AV block, renal failure (creatinine clearance less than 20 ml/min), severe liver dysfunction, psoriasis, restrictive cardiomyopathy, congenital heart defects or heart valve disease with severe hemodynamic disturbances, CHF with myocardial infarction within the last 3 months, strict diet. Use during pregnancy and breastfeeding. During pregnancy, the drug should be recommended for use only if the benefit to the mother outweighs the risk of side effects in the fetus and/or child. In general, beta blockers reduce blood flow to the placenta and may affect fetal development. Blood flow in the placenta and uterus should be monitored, as well as the growth and development of the unborn child should be monitored, and if adverse events occur in relation to pregnancy and/or the fetus, alternative therapeutic measures should be taken. The newborn should be carefully examined after birth. In the first three days of life, symptoms of bradycardia and hypoglycemia may occur. There is no data on the excretion of bisoprolol into breast milk. Therefore, taking the drug is not recommended for women during breastfeeding. If taking the drug during lactation is necessary, breastfeeding should be discontinued. Do not abruptly interrupt treatment with the drug or change the recommended dose without first consulting your doctor, as this may lead to a temporary deterioration in heart function. Treatment should not be interrupted suddenly, especially in patients with coronary artery disease. If discontinuation of treatment is necessary, the dose should be reduced gradually. At the initial stages of treatment with the drug, patients need constant monitoring. The drug should be used with caution in the following cases: diabetes mellitus with significant fluctuations in blood glucose concentration: symptoms of a pronounced decrease in glucose concentration (hypoglycemia) such as tachycardia, palpitations or increased sweating may be masked; strict diet; carrying out desensitizing therapy; AV block of the first degree; Prinzmetal's angina; mild to moderate peripheral arterial circulatory disorders (increased symptoms may occur at the beginning of therapy); psoriasis (including history). Respiratory system: for bronchial asthma or COPD, simultaneous use of bronchodilators is indicated. In patients with bronchial asthma, there may be an increase in airway resistance, which requires a higher dose of beta2-agonists. Allergic reactions: Beta blockers, including the drug, may increase sensitivity to allergens and the severity of anaphylactic reactions due to the weakening of adrenergic compensatory regulation under the influence of beta blockers. Therapy with epinephrine (adrenaline) does not always give the expected therapeutic effect. General anesthesia: When performing general anesthesia, the risk of beta-adrenergic receptor blockade should be taken into account. If it is necessary to discontinue drug therapy before surgery, this should be done gradually and completed 48 hours before general anesthesia. You should notify your anesthesiologist that you are taking the drug. Pheochromocytoma: in patients with an adrenal tumor (pheochromocytoma), the drug can only be prescribed while using alpha-blockers. Hyperthyroidism: when treated with the drug, symptoms of hyperthyroidism (hyperthyroidism) may be masked. Influence on the ability to drive vehicles and complex mechanisms. The drug does not affect the ability to drive vehicles, according to the results of a study in patients with coronary artery disease. However, due to individual reactions, the ability to drive vehicles or operate technically complex mechanisms may be impaired. Particular attention should be paid to this at the beginning of treatment, after changing the dose, and also when consuming alcohol at the same time.

Storage conditions
Store out of the reach of children at a temperature not exceeding 25 C.