Concor Cor, 30 pcs., 2.5 mg, film-coated tablets

Pharmacological properties of the drug Concor cor

Bisoprolol (INN - bisoprololum) is a selective β1-adrenergic receptor blocker. When used in therapeutic doses, it does not have BSA and clinically significant membrane-stabilizing properties. Reduces plasma renin activity, reduces myocardial oxygen demand, and reduces heart rate (at rest and during exercise). By blocking β1-adrenergic receptors of the heart in low doses, it reduces the catecholamine-stimulated formation of cAMP from ACE, reduces the intracellular current of calcium ions, and has a negative chrono-, dromo- and inotropic effect (inhibits conduction excitability, slows down AV conduction). 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. When increasing the dose above the therapeutic one, it has a β2-adrenergic blocking effect. Concor Cor has a hypotensive effect due to a decrease in cardiac output, inhibition of renin secretion by the kidneys, as well as an effect on the baroreceptors of the aortic arch and carotid sinus. In case of hypertension (arterial hypertension), the effect occurs after 2–5 days, stable effect occurs after 1–2 months. With prolonged use, bisoprolol reduces increased peripheral vascular resistance. When used in average therapeutic doses, in contrast to non-selective β-blockers, it has a less pronounced effect on organs containing β2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause delay sodium ions (Na+) in the body. The severity of the atherogenic effect does not differ from the effect of propranolol. After taking the drug orally, bisoprolol is well absorbed from the gastrointestinal tract. Bioavailability is about 90% and is independent of food intake. The maximum concentration is reached after 1–3 hours. Binding to blood plasma proteins is about 30%. The effect of primary passage through the liver is insignificant (about 10%). About 50% of bisoprolol is biotransformed in the liver with the formation of inactive metabolites. The main metabolites found in blood plasma and urine do not exhibit pharmacological activity. The pharmacokinetics of bisoprolol is linear. Its concentration in blood plasma is proportional to the administered dose in the dose range from 5 to 20 mg. The maximum concentration in blood plasma is reached after 2–3 hours. Bisoprolol is distributed quite widely. The volume of distribution is 3.5 l/kg. Communication with blood plasma proteins is about 35%. The total clearance is 15.6 ± 3.2 l/h, with renal clearance being 9.6 ± 1.6 l/h. The half-life is 10–12 hours. Approximately 98% is excreted from the body in the urine, 50% unchanged, the rest in the form of metabolites, approximately 2% of the dose is excreted in the feces. No dose adjustment is required for patients with mild to moderate hepatic or renal impairment.

Concor cor 2.5 mg 30 pcs. film-coated tablets

pharmachologic effect

Beta1-adrenergic blocker selective.

Composition and release form Concor cor 2.5 mg 30 pcs. film-coated tablets

Tablets - 1 tablet:

• active substance: bisoprolol fumarate - 2.5 mg;
• excipients: calcium hydrogen phosphate, anhydrous - 134.0 mg; corn starch, fine powder - 15 mg; colloidal silicon dioxide, anhydrous - 1.5 mg; microcrystalline cellulose - 10.0 mg; crospovidone - 5.5 mg; magnesium stearate - 1.5 mg;
• Film coating: hypromellose 2910/15 - 2.20 mg, macrogol-400 - 0.53 mg, dimethicone-100 - 0.11 mg, titanium dioxide (E 171) - 1.22 mg.

10 tablets per blister made of aluminum foil and PVC; 3 blisters along with instructions for use are placed in a cardboard box.

14 tablets per blister made of aluminum foil and PVC; 1 blister along with instructions for use is placed in a cardboard box.

25 tablets per blister made of aluminum foil and PVC; 2 blisters along with instructions for use are placed in a cardboard box.

30 tablets in a blister made of aluminum foil and PVC; 1 blister along with instructions for use is placed in a cardboard box.

When packaging the drug at the Russian enterprise Nanolek LLC

30 tablets in a blister made of aluminum foil and PVC; 1 or 2 blisters along with instructions for use are placed in a cardboard box.

Description of the dosage form

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

Directions for use and doses

Concor® Cor 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 Concor® Cor requires a special titration phase and regular medical supervision.

The precondition for treatment with Concor® Cor is stable chronic heart failure without signs of exacerbation.

Treatment of CHF 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. 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 Concor Cor 1 time per 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 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 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:

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 on the use of 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.

Pharmacodynamics

A selective beta1-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.

Indications for use Concor cor 2.5 mg 30 pcs. film-coated tablets

Chronic heart failure.

Contraindications

• Hypersensitivity to bioprolol 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 block;
• 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;
• 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).

With caution: carrying out desensitizing therapy, Prinzmetal's angina, hyperthyroidism, type I diabetes mellitus and diabetes mellitus with significant fluctuations in blood glucose concentration, AV block of the first degree, 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 chronic obstructive pulmonary disease, strict diet.

Application of Concor cor 2.5 mg 30 pcs. film-coated tablets 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 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 Concor® Cor is not recommended for women during breastfeeding. If taking the drug during lactation is necessary, breastfeeding should be discontinued.

special instructions

Do not interrupt treatment with Concor® Cor abruptly 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.

During 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 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 will require a higher dose of beta2-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 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 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. You should notify your anesthesiologist that you are taking the drug Concor® Cor.

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

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

Impact on the ability to drive vehicles and operate machinery

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.

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).

Side effects Concor cor 2.5 mg 30 pcs. film-coated tablets

The frequency of the adverse reactions listed below was determined according to the following: very common ≥ 1/10; often ≥ 1/100,

Central nervous system - Often: dizziness, headache; Rarely: loss of consciousness.

General disorders - Often: asthenia, increased fatigue.

Mental disorders - Uncommon: depression, insomnia; Rarely: hallucinations, nightmares.

On the part of the organ of vision - Rarely: reduction of lacrimation (should be taken into account when wearing contact lenses); Very rare: conjunctivitis.

From the organ of hearing - Rarely: hearing impairment.

From the cardiovascular system - Very often: bradycardia; Often: worsening symptoms of CHF; a feeling of coldness or numbness in the extremities, a pronounced decrease in blood pressure; Uncommon: AV conduction disturbance, 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 rare: 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)).

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 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 caution

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 enhance 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.

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, 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.

Use of the drug Concor cor

The tablets should be taken 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. 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.

The maximum recommended dose for the treatment of chronic heart failure is 10 mg of bisoprolol once a day. Patients are advised to take the dose of the drug selected by the doctor, unless adverse reactions occur. After starting treatment with the drug at a dose of 1.25 mg (1/2 t of Concor Cor tablet), the patient should be observed for about 4 hours (monitoring heart rate, blood pressure, conduction disturbances, signs of worsening heart failure). During or after the titration phase, a temporary worsening of heart failure symptoms, fluid retention, hypotension, or bradycardia may occur. In this case, it is recommended, first of all, to pay attention to the selection of the dosage of concomitant basic therapy (optimize the dose of the diuretic and/or ACE inhibitor) before reducing the dosage of Concor Cor. Treatment with Concor Cor should only be interrupted if absolutely necessary. After stabilization of the patient's condition, re-titration should be carried out, or treatment should be continued. No dose adjustment is usually required for patients with mild to moderate hepatic or renal impairment. For patients with a marked decrease in renal function (creatinine clearance less than 20 ml/min) and with severe liver dysfunction, the daily dose should not exceed 10 mg. In any case, the dose is selected individually. 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.

Concor® Cor

Termination of therapy and “withdrawal syndrome”

You should not abruptly interrupt treatment with bisoprolol 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 (increased severity of angina attacks, the development of myocardial infarction and the occurrence of ventricular arrhythmias in patients with coronary artery disease with sudden cessation of beta-blockers have been noted). If discontinuation of treatment is necessary, the dose of bisoprolol should be reduced gradually. In case of significant worsening of angina or development of acute coronary syndrome, bisoprolol should be temporarily resumed.

Diseases for which the drug should be used with caution

Bisoprolol 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 concentrations: bisoprolol may mask symptoms of hypoglycemia (a marked decrease in blood glucose concentrations), such as tachycardia, palpitations or increased sweating;

- strict diet;

— carrying out desensitizing therapy;

— atrioventricular block of the first degree;

- vasospastic angina (Prinzmetal's angina); cases of coronary spasm have been observed. Despite its high beta1 selectivity, angina attacks cannot be completely excluded when taking bisoprolol in patients with Prinzmetal's angina. You should take the drug with extreme caution;

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

- psoriasis (including history).

Diseases of the cardiovascular system

Beta blockers should not be used in decompensated chronic heart failure until the patient's condition has stabilized.

At the initial stages of using bisoprolol, patients need constant monitoring.

Beta blockers may cause bradycardia. If the resting heart rate decreases to less than 50-55 beats/min, the dose should be reduced or discontinued taking bisoprolol.

Like other beta blockers, bisoprolol may cause a prolongation of the PQ interval on the ECG. Bisoprolol should be used with caution in patients with first degree atrioventricular block.

Non-selective beta-blockers may increase the frequency and duration of anginal attacks in patients with vasospastic angina (Prinzmetal's angina) due to alpha-receptor-mediated coronary artery vasoconstriction. Cardioselective beta1-blockers (including bisoprolol) should be used with caution in vasospastic angina.

To date, there is insufficient data regarding the use of bisoprolol 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.

Respiratory system

Despite the fact that selective beta-blockers have a lesser effect on the function of the respiratory system than non-selective beta-blockers, patients with chronic obstructive pulmonary disease COPD and mild forms of bronchial asthma should be prescribed bisoprolol with extreme caution and only if possible the benefits of its use outweigh the potential risks. 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.

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).

Major surgery and general anesthesia

If surgical interventions are necessary, the anesthesiologist should be warned that the patient is taking beta-blockers (risk of drug interactions with the development of severe bradyarrhythmias, reduction of reflex tachycardia and arterial hypotension). It is recommended not to stop taking bisoprolol in the perioperative period unless clearly necessary (since beta-adrenergic receptor blockade reduces the risk of arrhythmias and myocardial ischemia during induction of anesthesia and tracheal intubation). If it is necessary to interrupt treatment with bisoprolol before surgery, the drug should be discontinued at least 48 hours before surgery.

Pheochromocytoma

In patients with pheochromocytoma, bisoprolol can only be prescribed while using alpha-blockers.

Thyrotoxicosis

With hyperthyroidism, beta-blockers (including bisoprolol) can mask tachycardia and reduce the severity of symptoms of thyrotoxicosis. Abrupt withdrawal of the drug can cause exacerbation of symptoms of the disease and the development of thyrotoxic crisis.

Hypersensitivity reactions

Beta blockers, including bisoprolol, may increase sensitivity to allergens and the severity of anaphylactic/hypersensitivity reactions due to decreased adrenergic compensatory regulation by beta blockers. The use of conventional therapeutic doses of egschnephrine (adrenaline) while taking beta-blockers does not always lead to the achievement of the desired clinical effect.

Caution should be exercised when prescribing bisoprolol to patients with a history of severe hypersensitivity reactions or undergoing desensitization.

Psoriasis

When deciding on the use of bisoprolol in patients with psoriasis, the expected benefits of the drug should be carefully weighed against the possible risk of exacerbation of psoriasis.

Contact lenses

Patients who use contact lenses should take into account that the use of beta-blockers may reduce the production of tear fluid.

Contraindications to the use of Concor Cor

Hypersensitivity to bisoprolol or any of the components of the drug and other beta-adrenergic receptor blockers; shock (cardiogenic shock), collapse; AV blockade II–III degree, sick sinus syndrome, severe sinoatrial block, bradycardia (heart rate ≤50 beats/min), Prinzmetal angina; arterial hypotension (systolic blood pressure ≤90 mm Hg), history of severe forms of asthma and COPD; late stages of peripheral circulatory disorders, Raynaud's disease; simultaneous use of MAO inhibitors (except for MAO type B inhibitors), psoriasis (including family history), pheochromocytoma, pregnancy and lactation.

Side effects of the drug Concor cor

From the nervous system: increased fatigue, dizziness, headache, sleep disturbances, depression may be observed (especially at the beginning of therapy), rarely - hallucinations (usually mild and disappear within 1-2 weeks), sometimes - paresthesia. On the part of the organ of vision: visual disturbances, decreased tear production (must be taken into account when wearing contact lenses), conjunctivitis. From the cardiovascular system: in some cases - orthostatic hypotension, bradycardia, AV conduction disturbances, decompensation of heart failure with the development of peripheral edema, at the beginning of treatment - deterioration of the condition of patients with intermittent claudication or Raynaud's syndrome. From the respiratory system: in isolated cases - shortness of breath (in patients prone to bronchospasm). From the gastrointestinal tract : in some cases - diarrhea, constipation, nausea, abdominal pain, increased activity of liver enzymes in the blood serum (AST, ALT), hepatitis. From the musculoskeletal system: in some cases - muscle weakness, cramps, arthropathy affecting one or more joints (mono- or polyarthritis). From the endocrine system: decreased glucose tolerance (with latent diabetes mellitus) and masking of signs of hypoglycemia, in some cases - increased TG levels in the blood, potency disorders. On the skin: sometimes - itching, skin hyperemia, increased sweating, rash. When treated with beta-adrenergic receptor blockers, hair loss, hearing impairment or tinnitus, weight gain, mood changes, short-term memory loss, allergic rhinitis, and priapism are observed in some cases.

Side effects

Side effects are rare, but they are not excluded:

• cramps, muscle weakness;
• bronchial asthma (exacerbation);
• sleep disorders;
• depressive states;
• headaches;
• dizziness;
• rarely – loss of consciousness;
• conjunctivitis;
• nausea;
• diarrhea;
• problems with potency;
• allergic reactions (itching, rashes, rhinitis of allergic origin).

Special instructions for the use of the drug Concor cor

Concor Cor should not be used during pregnancy and breastfeeding due to the lack of reliable clinical data confirming the safety of the drug. During pregnancy, Concor Cor should only be recommended if the benefit to the mother outweighs the risk of side effects to the fetus. In exceptional cases, the use of bisoprolol during pregnancy should be discontinued 72 hours before the expected due date due to the possibility of bradycardia, hypoglycemia and respiratory depression in the newborn. If discontinuation of the drug is not possible, then after birth the newborn should be under medical supervision. Symptoms of hypoglycemia may occur during the first 3 days. In some cases, beta-adrenergic receptor blockers may cause the development or exacerbation of psoriasis. In patients taking β-adrenergic blockers, due to weakened adrenergic feedback regulation, anaphylactic reactions may be more severe. Due to the individual nature of reactions to the drug, the ability to drive vehicles or operate machinery may be reduced. To a greater extent, this applies to the initial stage of treatment and changes in the dose of the drug, as well as with the simultaneous use of alcohol. There are no clinical data on the effectiveness and safety of Concor Cor in children.

special instructions

In some cases, there are no direct contraindications to the use of Concor. However, it should be taken with caution if you have the following disorders:

• following a strict diet (for example, after surgery, to correct weight);
• psoriasis;
• diabetes mellitus (if its course is accompanied by hypoglycemia);
• Prinzmetal's angina;
• AV block (first degree).

Interactions of the drug Concor cor

With simultaneous use, Concor Cor may enhance the effect of antihypertensive drugs. With the simultaneous use of bisoprolol and reserpine, methyldopa, clonidine or guanfacine, a sharp decrease in heart rate is possible. When Concor Cor is used together with clonidine, digitalis preparations, and guanfacine, cardiac conduction disorders may develop. When Concor is used together with verapamil or diltiazem and other antiarrhythmic drugs, a decrease in blood pressure is possible, and the risk of developing or worsening bradycardia, AV block, cardiac arrest and heart failure increases (IV administration of calcium channel blockers and antiarrhythmic drugs during Concor therapy should be avoided Cor).Nifedipine can lead to a significant decrease in blood pressure. Phenytoin with intravenous administration and drugs for inhalation general anesthesia (hydrocarbon derivatives) increase the severity of the cardiodepressive effect and the likelihood of a decrease in blood pressure when used while taking bisoprolol. The effectiveness of insulin and oral hypoglycemic drugs may change during treatment with Concor Cor (masks the symptoms of developing hypoglycemia: tachycardia, increased blood pressure). The clearance of lidocaine and xanthines may decrease 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 (Na+ retention, blockade of prostaglandin synthesis by the kidneys). With the simultaneous use of Concor Cor and sympathomimetics (including cough suppressants, eye drops and nasal drops), the effect of bisoprolol may be weakened. 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. Tri- 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; Rifampin shortens the half-life. With the simultaneous use of ergotamine derivatives (including ergotamine-containing migraine drugs) and Concor Cor, the severity of peripheral circulatory disorders may increase. With the simultaneous use of Concor Cor and rifampicin, the half-life of bisoprolol may slightly decrease (increasing the dose of Concor is usually not required).

Drug interactions

The drug is not recommended to be combined with medications such as Bisopropol. It leads to a decrease in the conductivity and contractility of the heart, which can lead to bradycardia. In turn, this will lead to vasodilation.

With caution, Concor is combined with drugs based on amiodarone and parasympathomimetic agents. If you use hypoglycemic drugs, their effect will increase. If used together with cardiac glycosides, symptoms of bradycardia will appear.

Parallel use of adrenergic agonists leads to an increase in blood pressure. If you use Mefloquine at the same time, this will again cause symptoms of bradycardia.

Overdose of Concor Cor, symptoms and treatment

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 and administration of adsorbent drugs; symptomatic therapy: in case of developed AV block, intravenous administration of 1–2 mg of atropine, epinephrine or placement of a temporary pacemaker; for ventricular extrasystole - lidocaine (class IA drugs are not used); with a pronounced decrease in blood pressure, the patient should be in a position with the foot end of the bed raised; if there are no signs of pulmonary edema - intravenous plasma replacement solutions; if ineffective - administration of epinephrine, dopamine, dobutamine (to maintain 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 - β2-adrenergic stimulants by inhalation.