Expiration date: 12/2025

The composition and form of issue:

Tablets, film-coated. 1 tablet contains active substance: hemifumarate bisoprolol (bisoprolol fumarate (2:1) 2.5 mg

excipients: calcium hydrogen phosphate anhydrous maize starch silica colloidal microcrystalline cellulose (MCC) crospovidone magnesium stearate 

film cover: 2910/15 hypromellose macrogol 400, Dimethicone 100 titanium dioxide (E171) 

in a blister of aluminum foil and PVC 10 PCs. in cardboard pack of 3, 5 or 10 blisters.

Description pharmaceutical form:

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

Pharmacokinetics:

Suction. Bisoprolol is almost completely (>90%) absorbed from the gastrointestinal tract. Its bioavailability due to low metabolism when "first pass" through the liver (approximately 10-15%) of about 85-90% after oral administration. Food intake does not affect bioavailability. Bisoprolol exhibits linear kinetics and concentrations in plasma proportional to the administered dose in the dose range of 5 to 20 mg. Cmax in plasma achieved through 2-3 h.

Distribution. Bisoprolol is distributed quite widely. The distribution volume is 3.5 l/kg. Linking blood plasma proteins is about 35% capture of blood cells is not observed.

Metabolism. Metabolized via the oxidative pathway without subsequent conjugation. All metabolites have a strong polarity and are excreted by the kidneys. The main metabolites detected in plasma and urine, does not exhibit a pharmacological activity. The data obtained in the result of experiments with human liver microsomes in vitro indicate that bisoprolol is metabolized primarily via CYP3A4 (about 95%), a CYP2D6 plays only a small role.

Excretion. The clearance of bisoprolol is determined by the balance between the excretion of it through the kidneys as unchanged substance (about 50%) and oxidation in the liver (about 50%) to metabolites that then are excreted by the kidneys. Total Cl — (15,6±3,2) l/h, and renal Cl — (9,6±1,6) l/h. T1/2 is 10-12 hrs

Description pharmacological action:

Selective beta1-blocker without own sympathomimetic activity, has membrane stabilizing effect. Reduces renin activity of blood plasma, reduces the need heart of oxygen, reduces the heart rate (at rest and during exercise). It has hypotensive, antiarrhythmic and antianginal effects. Blocking in low doses beta1-adrenergic receptors of the heart, reduces catecholamines stimulated camp formation from ATP, reduces intracellular current of calcium ions, has a negative Chrono-, dromo-, batmo - and inotropic effect (it inhibits conduction and excitability, slows AV conduction).

With increasing doses above the therapeutic having beta2-adrenoblokirtee action.

The CSO at the beginning of the drug in the first 24 h, increases slightly (as a result of reciprocal increase of activity of alpha adrenergic receptors), which, through 1-3 day returns to the source, and prolonged assignment is reduced.

Hypotensive effect is associated with a decrease in minute volume of blood, sympathetic stimulation of peripheral vessels, decreased activity of the renin-angiotensin system (is of great significance for patients with initial hypersecretion of renin), restoring sensitivity in response to decreased blood pressure and effects on the Central nervous system. In arterial hypertension effect occurs in 2-5 days, stable effect — in 1-2 months.

Antianginal effect is due to reduction of requirement of a myocardium in oxygen as a result of deceleration in heart rate, slight decrease in contractility, lengthening of diastole, improved myocardial perfusion. Antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased camp content, arterial hypertension), decrease in speed spontaneous initiation sinusnogo and ectopiceski drivers rhythm and slowing AV conduction (mainly in the anterograde and to a lesser extent, in the retrograde directions through the AV node) and on additional ways.

When used in high therapeutic doses, unlike nonselective beta - blockers, has a less pronounced effect on bodies containing beta2-adrenergic receptors (pancreas, skeletal muscle, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause the delay of sodium ions (Na+) in the body.

Indications:

• hypertension
  
• coronary heart disease (prevention of angina attacks)
  
• chronic heart failure.
  

Contraindications:

• hypersensitivity to bisoprolol or to any component of the drug (see "Composition and form") and other beta-blockers
  
• acute heart failure, chronic heart failure decompensation
  
• shock caused by disorders of cardiac function (cardiogenic shock), collapse
  
• AV blockade II and III degree, without pacemaker
  
• syndrome weakness sinusnogo hub
  
• sinoatrial block
  
• bradycardia (heart rate <50 beats/min.)
  
• marked reduction in blood pressure (SBP <90 mm Hg. article)
  
• severe forms of bronchial asthma and COPD in history
  
• late stages of peripheral circulatory disorders, Raynaud's disease,
  
• pheochromocytoma (without the simultaneous use of alpha-blockers)
  
• metabolic acidosis
  
• simultaneous reception MAO inhibitors except MAO-b
  
• the age of 18 years (efficacy and safety not established).
  

With caution:

• liver failure
  
• chronic renal failure
  
• Prinzmetal's angina
  
• myasthenia gravis
  
• thyrotoxicosis
  
• diabetes
  
• AV blockade I of a degree
  
• depression (including in history)
  
• psoriasis
  
• old age.
  

Application of pregnancy and breast-feeding:

During pregnancy Concor should be recommended only if the benefit to the mother outweighs the risk of side effects in the fetus.

As a rule, beta-blockers reduce blood flow to the placenta and can affect fetal development. You should carefully monitor the blood flow in the placenta and uterus, as well as to monitor the growth and development of the unborn child, and in the case of dangerous manifestations in relation to pregnancy or foetus, alternative therapeutic measures.

You should carefully examine the newborn after birth. In the first 3 days of life can cause symptoms reduce the glucose level in blood and heart rate.

Data on the excretion of bisoprolol in human breast milk or the safety of bisoprolol exposure in infants not. Therefore, the drug Concor is not recommended to women during the breastfeeding period.

Side effects:

Frequency of adverse reactions given below were determined according to the following: very often (&ge1/10), often (>1/100, <1/10) uncommon (>1/1000, <1/100) rare (>1/10000, <1/1000) very rare (<1/10000, including individual messages).

Cardiovascular system: very often — reduced heart rate (bradycardia, especially in patients with chronic heart failure) often — hypotension (especially in patients with chronic heart failure), manifestation of angiospasm (increased peripheral circulatory disorders, cold sensation in the extremities — paresthesia) rarely, violation of AV conduction, orthostatic hypotension, decompensation of heart failure with the development of peripheral edema.

Nervous system: at the beginning of treatment may temporarily appear disorders of the CNS often dizziness, headache, asthenia, fatigue, sleep disturbances, and mental disorder (often depression rarely — hallucinations, nightmares, convulsions). Usually these effects are light in nature and disappear, usually within 1-2 weeks after the start of treatment.

Visual organs: rare — impaired vision, reduction of tearing (to consider when wearing contact lenses) very rare — conjunctivitis.

Respiratory system: rarely — allergic rhinitis rarely, bronchospasm in patients with bronchial asthma or obstructive Airways disease.

Tract: often — nausea, vomiting, diarrhea, constipation, dryness of the mucous membrane of the oral cavity rarely — hepatitis.

Musculoskeletal system: infrequently — muscle weakness, cramps in calf muscles, arthralgia.

Allergic reactions: seldom — hypersensitivity reactions such as itching, redness, sweating, rash, very rarely — alopecia. Beta-blockers can exacerbate psoriasis.

Urogenital system: very rarely — violation of potency.

Laboratory parameters: rare — increased level of liver enzymes in the blood (ACT, ALT), increased level of triglycerides in the blood. In some cases — thrombocytopenia, agranulocytosis.

Drug interactions:

The efficacy and tolerability of drugs can affect the simultaneous reception of other medicines. This interaction can occur also in cases when 2 drugs are taken through a short period of time. The doctor must be informed that you are taking other drugs, even if you take them without a prescription.

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

Iodine-containing radiopaque diagnostic agents for/in the introduction increases the risk of anaphylactic reactions.

Phenytoin in the on/in the introduction, drugs for inhalation General anesthesia (derivatives of hydrocarbons) increase the intensity of cardiodepressive actions and reduce the likelihood of AD.

The effectiveness of insulin and oral hypoglycemic drugs can vary in the treatment of bisoprololum (masks the symptoms of developing hypoglycemia: tachycardia, the AD).

The clearance of lidocaine and xantinov (except difillina) may be reduced in connection with a possible increase in their concentration in blood plasma, especially in patients with initially increased clearance of theophylline under the influence of Smoking.

NSAIDs, corticosteroids and estrogens attenuate the hypotensive effect of bisoprolol (delay of Na+, blockade of PG synthesis by the kidney).

Cardiac glycosides, methyldopa, reserpine, and guanfacine, CCB (verapamil, diltiazem), amiodarone and other antiarrhythmic agents increase the risk of developing or exacerbating bradycardia, AV block, cardiac arrest and heart failure.

Nifedipine can lead to significant reduction of AD.

Diuretics, clonidine, sympatholytic, hydralazine, and other antihypertensive drugs can lead to excessive reduction of AD.

Effects of non-depolarizing muscle relaxants and anticoagulant effect of coumarins during treatment with bisoprolol can be extended.

Three - and tetracyclic antidepressants, antipsychotic means (neuroleptics), ethanol, sedatives and hypnotics drugs increase oppression CNS.

Not recommended simultaneous application with MAO inhibitors because of significant increase gipotenzivnogo actions. The break in treatment between receiving MAO inhibitors and bisoprolol must be not less than 14 days.

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

Ergotamine increases risk of peripheral circulation sulfasalazine bisoprolol improves concentration in plasma rifampicin shortens the half-life.

Method of application and dose:

Inside, the tablets should be taken without chewing, with a small amount of liquid in the morning before Breakfast, during, or after, 1 time per day.

Treatment of hypertension and angina

In all cases the mode of reception and dose selects the physician for each patient individually, taking into account in particular the variation and condition of the patient.

The usual starting dose is 5 mg (1 table. Konkor 5 mg) 1 times a day. If necessary, the dosage can be increased to 10 mg 1 times a day.

In the treatment of hypertension and angina the maximum recommended dose of 20 mg Concor 1 time a day.

echenie chronic heart failure

Initiating treatment of chronic heart failure drug Concor requires mandatory holding of a special phase titration and regular medical monitoring.

Preconditions for treatment with Concor the following:

- congestive heart failure without evidence of exacerbation in the preceding 6 months,

- virtually unchanged basic therapy during the previous 2 weeks,

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

The treatment of chronic heart failure with Concor starts in accordance with the following scheme of titration. This may require individual adjustment depending on how well the patient takes the prescribed dose, i.e. the dose can be increased only if the previous was well tolerated.

Table

The dosing regimen in the treatment of chronic heart failure

Submission deadlines	The dosage, mg/day
1st week	the initial dose — 1,25
2nd week	2,5
3rd week	3,75
4–7th week	5
8–11th week	7,5
from 12th week	10 (as maintenance therapy*)

* To ensure the above titration in the initial stages of treatment, it is recommended to use the drug Concor Cor.

The maximum recommended dose in the treatment of chronic heart failure 10 mg of Concor 1 time a day.

Patients are encouraged to take selected doctor the dose, if you do not have adverse reactions.

After the start of drug treatment at a dose of 1.25 mg (1/2 table. drug Concor Cor) the patient should be observed for approximately 4 h (control heart rate, AD, violations conductivity, signs of worsening heart failure).

During the titration phase or after it can have temporary worsening of heart failure, fluid retention in the body, hypotension, or bradycardia. In this case it is especially recommended to pay attention to the selection of the dosage of concomitant baseline therapy (to optimize the dose of diuretic and/or ACE inhibitor) before the reduction in dosage of Concor. Treatment with Concor should interrupt only if absolutely necessary.

After stabilization of the patient's state should re-titration, or to continue treatment.

The treatment duration in all indications

Treatment with Concor is usually long-term therapy.

If necessary, the treatment can be interrupted and resumed with the observance of certain rules.

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

Special groups of patients

Violation of the kidney or liver

Treatment of hypertension or angina:

- when liver dysfunction or kidney disease mild or moderate degree usually does not require dose adjustment

- when expressed violations kidney function (Cl creatinine <20 ml/min) and in patients with severe liver disease maximum daily dose of 10 mg.

Elderly patients: dose adjustment is not required.

Overdose:

Symptoms: arrhythmia, ventricular arrythmia, expressed aetiology, AV blockade, expressed lower AD, acute heart failure, hypoglycemia, acrocyanosis, shortness of breath, bronchospasm, dizziness, fainting, seizures.

Treatment: gastric lavage and the appointment of adsorbing drugs symptomatic therapy: with advanced AV blockade — in/in the introduction 1-2 mg of atropine, epinephrine or staging a temporary pacemaker with ventricular arrhythmia — lidocaine (class IA drugs do not apply) when expressed lower AD — the patient should be in Trendelenburg position if there are no signs of pulmonary edema — plazmozameshchath solutions in/, the ineffectiveness — introduction epinephrine, dopamine, dobutamine (for maintaining chronotropic and inotropic actions and resolve expressed lower AD) heart failure — cardiac glycosides, diuretics, glucagon in convulsions — in/diazepam with bronchospasm — beta2-agonists inhalation.

Special instructions:

It is not recommended to interrupt the treatment abruptly and change to the recommended dosage without prior consultation with a doctor, as this may lead to temporary impairment of heart activity. Treatment should not be interrupted suddenly, especially in patients with coronary artery disease. If a treatment is necessary, the dosage should be reduced gradually.

Monitoring of patients taking Concor should include measurement of HR and AD (at the beginning of treatment — daily, then 1 once in 3-4 mo), the ECG, determination of blood glucose in patients with diabetes mellitus (1 once in 4-5 mo). In elderly patients it is recommended to monitor kidney function (1 once in 4-5 mo).

Should teach the patient methods of calculating heart rate and instruct on the need of medical advice in heart rate <50 beats/min.

Before treatment is recommended study of respiratory function in patients with a history of bronchopulmonary history.

Patients using contact lenses should take into account that the treatment may decrease the production of tear fluid.

When used in patients with pheochromocytoma there is a risk of paradoxical hypertension (if not previously achieved effective alpha adrenoblokada).

Thyrotoxicosis Concor may mask certain clinical signs of hyperthyroidism (e.g. tachycardia). Abrupt withdrawal of the drug in patients with thyrotoxicosis is contraindicated, because it can reinforce the symptoms.

At diabetes can mask the tachycardia, caused by hypoglycemia. Unlike nonselective beta-blockers hardly enhances insulin-induced hypoglycemia and delay recovery of the glucose concentration in the blood to normal levels.

At the same time taking clonidine its reception can be terminated only a few days after the abolition of Concor.

Perhaps the increased severity of hypersensitivity reactions and lack of effect of conventional doses of epinephrine with aggravated allergic anamnesis.

If necessary for a planned surgical treatment, the drug should be discontinued for 48 h before General anesthesia. If the patient has taken the drug before surgery, he should choose drugs for General anesthesia with minimal negative inotropic effects.

Reciprocal activation of the vagus nerve can eliminate/atropine (1-2 mg).

Drugs, reducing stocks of catecholamines (e.g. reserpine), may enhance the action of beta-adrenoblokatorov, therefore, patients, accepting such combination drugs, should be under constant supervision of a doctor to identify expressed lower AD or bradycardia.

Patients with bronchospastic diseases you can assign a cardioselective blocker in case of intolerance and/or ineffectiveness of other antihypertensive agents. When the dose of the drug there is a risk of bronchospasm.

In the case of elderly patients increasing bradycardia (heart rate <50 beats/min), expressed lower AD (SBP <100 mm Hg. Hg), AV blockade, it is necessary to reduce the dose or stop the treatment.

It is recommended to discontinue therapy in the development of depression.

Do not abruptly discontinue the treatment because of the risk of severe arrhythmias and myocardial infarction. The abolition of the drug are gradually, reducing the dose for 2 weeks or more (reduce the dose 25% in 3-4 day). It should stop the drug before the study of blood and urine catecholamines, normetanephrine and vanillylmandelic acid, titles of antinuclear antibodies.

Effects on ability to drive and use complex mechanisms

Bisoprolol does not affect the ability to drive in the study of patients suffering from diseases of the coronary vessels of the heart. However, due to the individual reactions, the ability to drive or to work with technically complex mechanisms can be broken. It should pay special attention at the beginning of treatment, after change of dose, as well as the simultaneous use of alcohol.