Concor, 5 mg, film-coated tablets, 90 pcs.

Concor, 5 mg, film-coated tablets, 90 pcs.

Inside.

Concor® 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.

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® 1 time per day. If necessary, the dose can be increased to 10 mg 1 time per day.

For the treatment of arterial hypertension and stable angina, the maximum recommended dose is 20 mg of Concor® once a day.

CHF

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

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

Treatment of CHF 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 tablet dosage form, 2.5 mg, in the initial stages of treatment. 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 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 the treatment of CHF is 10 mg of Concor® 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 already from the 1st day of using the drug.

If the patient does not tolerate the maximum recommended dose of the drug, 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 for use of the drug Concor®

Treatment with the drug is usually long-term therapy.

Special patient groups

Impaired kidney or liver function:

- if there is mild or moderate impairment of liver or kidney function, dosage adjustment is usually not required;

- in case of severe renal dysfunction (Cl creatinine <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 Concor® 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 Concor® 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.

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.