Concor film-coated tablets 10 mg blister 30 pcs

Pharmacodynamics. Bisoprolol is a highly selective β1-adrenoceptor blocker. It has no intrinsic sympathomimetic activity and clinically pronounced membrane-stabilizing properties. The drug has a very low affinity for β2-receptors of bronchial and vascular smooth muscle, as well as for β2-receptors involved in metabolic regulation. Thus, bisoprolol does not affect airway resistance and β2-mediated metabolic effects. The selectivity of bisoprolol for β1-adrenoceptors extends beyond the therapeutic dose range.

Bisoprolol does not have a pronounced negative inotropic effect.

The maximum effect of bisoprolol occurs 3-4 hours after oral administration. T _½ is 10-12 hours, which results in 24-hour efficacy after a single dose. The maximum antihypertensive effect is achieved after 2 weeks of administration.

In intensive therapy in patients with coronary artery disease without chronic heart failure, bisoprolol reduces cardiac output and myocardial oxygen demand by reducing heart rate and stroke volume. With prolonged therapy, increased peripheral resistance decreases. Also, the antihypertensive effect of β-adrenoceptor blockers is based on the mechanism of reducing renin activity in blood plasma.

Bisoprolol inhibits the response to sympathoadrenergic activity by blocking cardio-β ₁ -receptors. This leads to a slowdown in heart rate and a decrease in myocardial contractile function, a decrease in myocardial oxygen demand. This achieves the desired effect in patients with angina pectoris and coronary artery disease.

Pharmacokinetics. Absorption. After oral administration, more than 90% of bisoprolol is absorbed in the gastrointestinal tract. Absorption is independent of food intake. The first-pass effect is ≤10%. Bioavailability is about 90%.

Distribution: The volume of distribution is 3.5 l/kg. Plasma protein binding is about 30%.

Metabolism and excretion. Bisoprolol is excreted from the body in two ways: 50% is metabolized in the liver with the formation of inactive metabolites and excreted by the kidneys, 50% is excreted by the kidneys unchanged. The total clearance of bisoprolol is 15 l / h. Due to the long T _½ (10-12 h) the drug retains a therapeutic effect for 24 h when used once a day.

Linearity. The pharmacokinetics of bisoprolol are linear, and their parameters do not depend on age.

Special patient groups. Since bisoprolol is excreted from the body by the kidneys and liver equally in patients with impaired liver function or renal function, correction of the dosage regimen is not required. Pharmacokinetics in patients with stable chronic heart failure and with impaired liver or kidney function have not been studied. In patients with chronic heart failure of functional class III (according to NYHA), the level of bisoprolol in the blood plasma is higher and T _½ is longer compared to healthy volunteers. C _max in the blood plasma in the equilibrium state is 64 ± 21 ng / ml at a daily dose of 10 mg and T _½ 17 ± 5 h.

Ag; coronary artery disease (angina); chronic heart failure with left ventricular systolic dysfunction in combination with ACE inhibitors, diuretics, and if necessary, cardiac glycosides.

Concor should be taken without chewing in the morning on an empty stomach or during breakfast, with a small amount of liquid.

AH; coronary artery disease (angina pectoris). Treatment should be started gradually with low doses followed by an increase in the dose. The recommended dose is 5 mg (1 tablet of Concor 5 mg) per day. For mild hypertension (diastolic blood pressure up to 105 mm Hg), a dose of 2.5 mg is suitable.

If necessary, the daily dose may be increased to 10 mg (1 tablet of Concor 10 mg). Further dose increases are justified only in exceptional cases.

The maximum recommended dose is 20 mg/day.

The dose is adjusted individually by the doctor depending on the pulse rate and therapeutic benefit.

Chronic heart failure with left ventricular systolic dysfunction in combination with ACE inhibitors, diuretics, and if necessary, cardiac glycosides. Standard therapy for chronic heart failure: ACE inhibitors (or angiotensin receptor blockers in case of intolerance to ACE inhibitors), β-adrenoceptor blockers, diuretics, and, if necessary, cardiac glycosides.

Concor is prescribed for the treatment of patients with chronic heart failure without signs of exacerbation.

Therapy should be carried out by a doctor with experience in the treatment of chronic heart failure.

Treatment of patients with stable chronic heart failure with Concor begins according to the titration scheme below and may be adjusted depending on individual body responses:

• 1.25 mg* bisoprolol fumarate once daily for 1 week, if well tolerated, increase to
• 2.5 mg* bisoprolol fumarate once daily for the next 1 week, if well tolerated, increase to
• 3.75 mg* bisoprolol fumarate once daily for the next 1 week, if well tolerated, increase to
• 5 mg bisoprolol fumarate once daily for the next 4 weeks, if well tolerated, increase to
• 7.5 mg bisoprolol fumarate once daily for the next 4 weeks, if well tolerated, increase to
• 10 mg bisoprolol fumarate once daily as maintenance therapy.

* At the beginning of therapy for chronic heart failure, it is recommended to use Concor Cor film-coated tablets, 2.5 mg.

The maximum recommended dose of bisoprolol fumarate is 10 mg once daily.

During the titration phase, monitoring of the following vital signs (BP, HR) and symptoms of progression of heart failure is necessary. Symptoms may develop from the first day of treatment.

Treatment modification. If the maximum recommended dose is not tolerated, a gradual dose reduction may be considered. If during or after the titration phase there is a gradual worsening of heart failure, hypotension or bradycardia, dose adjustment is recommended, which may require a temporary reduction in the bisoprolol dose or possibly discontinuation of treatment. After stabilization, the possibility of reinitiating bisoprolol treatment should always be considered.

Treatment with the drug should not be stopped abruptly, especially in patients with coronary artery disease, as this may lead to a deterioration in the patient’s condition. If necessary, it is recommended to discontinue treatment slowly, gradually reducing the dose (for example, reducing the dose by half every week).

Treatment of stable chronic heart failure is usually long-term.

The course of treatment with Concor is long and depends on the nature and severity of the disease.

Patients with hepatic and renal insufficiency

AH; CHD. For patients with mild to moderate hepatic or renal impairment, dose adjustment is usually not necessary. In patients with severe renal impairment (creatinine clearance 20 ml/min) and severe hepatic impairment, the dose should not exceed the daily dose of 10 mg Concor. There are limited data on the use of bisoprolol in patients on dialysis. There is no need to change the dosage regimen.

Chronic heart failure. There are no data on the pharmacokinetics of bisoprolol in patients with chronic heart failure concomitant with impaired liver and/or kidney function, therefore, the dose should be increased with caution.

Elderly patients do not require dose adjustment.

Adverse effects are classified by frequency of occurrence into the following categories: very common (≥1/10), common (≥1/100 and 1/10), uncommon (≥1/1000 and 1/100), rare (≥1/10,000 and 1/1000), very rare (1/10,000), unknown (frequency not determined).

On the part of the heart: very often – bradycardia (in patients with chronic heart failure); often – signs of worsening heart failure (in patients with chronic heart failure); infrequently – AV conduction disorders, bradycardia (in patients with arterial hypertension or coronary artery disease), signs of worsening heart failure (in patients with arterial hypertension or coronary artery disease).

From the nervous system: often – dizziness *, headache *; rarely – syncope.

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

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

On the part of the respiratory system: infrequently – bronchospasm in patients with bronchial asthma or a history of chronic obstructive respiratory diseases; rarely – allergic rhinitis.

Gastrointestinal tract: often – nausea, vomiting, diarrhea, constipation.

Skin and connective tissue disorders: rarely – hypersensitivity reactions, including itching, redness, rash; very rarely – alopecia. When treated with β-adrenergic blockers, the condition of patients with psoriasis may worsen in the form of a psoriatic rash.

Musculoskeletal system: infrequently – muscle weakness, cramps.

On the part of the liver: rarely – hepatitis.

Vascular disorders: often – feeling of coldness or numbness in the extremities, arterial hypotension (in patients with chronic heart failure); infrequently – orthostatic hypotension (in patients with chronic heart failure), arterial hypotension (in patients with arterial hypertension or coronary artery disease).

From the reproductive system: rarely – impaired potency.

Mental disorders: infrequently – depression, sleep disorders; rarely – nightmares, hallucinations.

Laboratory indicators: rarely – increased TG levels in the blood, increased activity of liver enzymes in blood plasma (AST, ALT).

General disorders: often – asthenia (in patients with chronic heart failure), fatigue *; infrequently – asthenia (in patients with hypertension and coronary artery disease).

*Applies only to patients with hypertension or coronary artery disease. These symptoms usually occur at the beginning of therapy, are mild, and disappear within the first 1-2 weeks.

In case of side effects or adverse reactions, you should immediately inform your doctor.

Treatment of stable chronic heart failure with bisoprolol should begin with a titration phase.

In patients with coronary artery disease, treatment should not be stopped abruptly without necessity, as this may lead to transient deterioration of the condition. Initiation and discontinuation of bisoprolol treatment requires regular monitoring.

Currently, there is insufficient therapeutic experience in the treatment of heart failure in patients with the following diseases and pathological conditions: type 1 diabetes mellitus (insulin-dependent), severe renal impairment, severe hepatic impairment, restrictive cardiomyopathy, congenital heart disease, hemodynamically significant acquired valvular heart disease, myocardial infarction within the last 3 months.

The drug should be used with caution in patients with conditions such as:

• bronchospasm (with asthma, obstructive airway diseases);
• diabetes mellitus with significant fluctuations in blood glucose levels, while symptoms of hypoglycemia (tachycardia, palpitations, increased sweating) may be hidden;
• strict diet;
• desensitization. Like other β-adrenergic blockers, bisoprolol may increase sensitivity to allergens and increase the severity of anaphylactic reactions. In such cases, treatment with adrenaline does not always give a positive therapeutic effect;
• First degree AV block;
• Prinzmetal’s angina;
• Obliterating peripheral arterial diseases (at the beginning of therapy, complaints may worsen);
• general anesthesia.

In patients undergoing general anesthesia, the use of β-adrenergic blockers reduces the risk of arrhythmia and myocardial ischemia during induction of anesthesia, intubation, and the postoperative period. It is recommended to continue the use of β-adrenergic blockers in the perioperative period. It is imperative to warn the anesthesiologist about the use of β-adrenergic blockers, since the doctor must take into account the potential interaction with other drugs, which can lead to bradyarrhythmia, reflex tachycardia, and a decrease in the ability of the reflex mechanism to compensate for blood loss. If bisoprolol is discontinued before surgery, the dose should be gradually reduced and the drug should be discontinued 48 hours before general anesthesia.

Combinations of bisoprolol with calcium antagonists of the verapamil or diltiazem group, with class I antiarrhythmic drugs and with centrally acting antihypertensive agents are not recommended (see Interaction with other drugs).

Although cardioselective β-adrenergic (β ₁₎ blockers have less effect on lung function than non-selective β-blockers, their use, like all β-adrenergic blockers, should be avoided in obstructive airway diseases unless there are compelling reasons for therapy. If necessary, Concor should be used with caution. In patients with obstructive airway diseases, treatment with bisoprolol should be started at the lowest possible dose and patients should be monitored for the appearance of new symptoms (such as dyspnea, exercise intolerance, cough).

_{In patients with asthma or other COPD conditions that may cause symptoms, concomitant bronchodilator therapy is indicated. In some cases, higher doses of β2} -sympathomimetics may be required in patients with asthma due to increased airway resistance while taking the drug .

Patients with psoriasis (including those with a history of psoriasis) are prescribed β-adrenergic blockers (e.g. bisoprolol) after careful consideration of the benefit/risk ratio.

Patients with pheochromocytoma are prescribed Concor only after the appointment of therapy with α-adrenoceptor blockers. Symptoms of thyrotoxicosis may be masked by taking the drug. When using Concor, a positive result may be obtained during doping control.

Use during pregnancy and breastfeeding. Pregnancy. Bisoprolol has pharmacological properties that may have a harmful effect on the course of pregnancy and/or the development of the fetus/newborn. As a rule, β-adrenergic blockers reduce placental blood flow, which can cause intrauterine growth retardation, intrauterine death, miscarriage or premature birth. Adverse effects in the fetus and newborn (e.g. hypoglycemia, bradycardia) may develop. If treatment with β-adrenergic blockers is necessary, it is preferable that it be a selective β ₁ -adrenergic blocker.

During pregnancy, the drug should be used only if the expected benefit to the mother outweighs the potential risk to the fetus. It is necessary to monitor uteroplacental blood flow and fetal growth. In case of harmful effects on the course of pregnancy or the fetus, alternative treatment should be considered.

After delivery, the newborn should be closely monitored. Symptoms of hypoglycemia and bradycardia can be expected during the first 3 days.

Breastfeeding. There is no data on the excretion of bisoprolol into breast milk, therefore it is not recommended to use Concor during breastfeeding.

Children. Clinical data on the efficacy and safety of the drug in children are lacking, therefore the drug should not be used in this category of patients.

Ability to influence the reaction rate when driving vehicles or working with other mechanisms. During studies involving patients with coronary artery disease, the drug did not affect the ability to drive vehicles. However, in individual cases, the drug may affect the ability to drive vehicles or work with complex mechanisms. Particular attention should be paid at the beginning of treatment, when changing the dose of the drug or when interacting with alcohol.

Combinations that are not recommended for use

Treatment of chronic heart failure. Class I antiarrhythmics (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): possible potentiation of the effect on AV conduction and increased severity of the negative inotropic effect.

All indications. Calcium antagonists such as verapamil, to a lesser extent diltiazem: negative effect on myocardial contractile function and AV conduction. Intravenous administration of verapamil can lead to severe hypotension and AV block.

Centrally acting antihypertensives (clonidine, methyldopa, moxonidine, rilmenidine): possible worsening of heart failure due to decreased central sympathetic tone (decreased heart rate and cardiac output, vasodilation). Abrupt withdrawal of the drug, especially if preceded by withdrawal of β-adrenergic blockers, may increase the risk of rebound hypertension.

Combinations to be used with caution

Treatment of hypertension or coronary artery disease (angina pectoris). Class I antiarrhythmics (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): possible potentiation of the effect on AV conduction and increased severity of the negative inotropic effect.

All indications. Dihydropyridine calcium antagonists (e.g. nifedipine, felodipine, amlodipine) may increase the risk of hypotension. The possibility of an increased negative effect on myocardial inotropic function in patients with heart failure cannot be excluded.

Class III antiarrhythmic drugs (e.g. amiodarone) may increase the negative effect on AV conduction.

Topical β-adrenergic blockers (e.g. contained in eye drops for the treatment of glaucoma): possible enhancement of the systemic effects of bisoprolol.

Parasympathomimetics: AV conduction time may be increased and the risk of bradycardia may increase.

Insulin and oral antidiabetic agents: increased hypoglycemic effect. Blockade of β-adrenergic receptors may mask the symptoms of hypoglycemia.

Anesthetics: increased risk of myocardial depression and hypotension (see Precautions).

Cardiac glycosides: decrease in heart rate, increase in AV conduction time.

NSAIDs may weaken the hypotensive effect of bisoprolol.

β-Sympathomimetics (e.g. orciprenaline, isoprenaline, dobutamine): use in combination with Concor may lead to a decrease in the therapeutic effect of both drugs. For the treatment of allergic reactions, the use of higher doses of adrenaline may be required.

Sympathomimetics that activate α- and β-adrenergic receptors (e.g. adrenaline, noradrenaline): α-adrenergic mediated vasoconstriction may occur, leading to increased blood pressure and increased intermittent claudication. This interaction is more likely with non-selective β-adrenergic blockers.

When used simultaneously with antihypertensive agents and agents that have a hypotensive effect (e.g. tricyclic antidepressants, barbiturates, phenothiazines), the risk of hypotension may be increased.

possible combinations

• Mefloquine may increase the risk of developing bradycardia.
• MAO inhibitors (except MAO inhibitors type B) enhance the hypotensive effect of β-adrenergic blockers, but there is a risk of developing hypertensive crisis.

Symptoms. In case of overdose (for example, a daily dose of 15 mg instead of 7.5 mg), cases of third-degree AV block, bradycardia and dizziness have been recorded. Frequent signs of overdose of β-adrenergic blockers are bradycardia, hypotension, acute heart failure, hypoglycemia and bronchospasm. Several cases of overdose in patients with AG and/or coronary artery disease (maximum dose – 2000 mg of bisoprolol) are currently known. Bradycardia and/or hypotension were noted. All patients recovered. There is a wide variability in individual sensitivity to a single high dose of bisoprolol, patients with heart failure may be more sensitive to the drug. Therefore, treatment should be started with a gradual increase in dose (see application).

Treatment. In case of overdose, discontinue treatment with the drug and provide supportive and symptomatic therapy. There is limited evidence that bisoprolol is difficult to dialyze. In case of suspected overdose, the following general measures should be considered, based on the expected pharmacological effect and recommendations for other β-adrenergic blockers.

In case of bradycardia: IV atropine. If there is no reaction, isoprenaline or another drug with a positive chronotropic effect is administered with caution. In exceptional cases, transvenous administration of an artificial pacemaker may be necessary.

For hypotension: IV fluids and vasoconstrictors. IV glucagon may be useful.

For AV block II and III degree: careful observation and infusion of isoprenaline or transvenous introduction of a pacemaker.

In case of exacerbation of chronic heart failure: administration of diuretics, inotropic drugs, vasodilators.

For bronchospasm: bronchodilators (e.g. isoprenaline), β2 _{-adrenomimetics} and/or aminophylline.

For hypoglycemia: intravenous glucose administration.

At a temperature not exceeding 30 °C.