Cordinorm: instructions for use, indications, reviews, price and analogues

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Selective beta1-blocker without endogenous sympathomimetic action and membrane stabilizing properties. By inhibiting β1-adrenergic receptors of the heart , the active substance reduces the catecholamine-stimulated formation of cAMP from normal ATP and reduces the intracellular transport of calcium ions. It has a negative chronotropic, dromotropic, bathmotropic and inotropic effect, slows down AV conduction, inhibits conduction and excitability, reduces the heart's need for oxygen. Reduces heart rate at rest and during exercise. Reduces the effects renin .

With increasing doses, bisoprolol demonstrates a beta2-adrenergic blocking effect.

In the first 24 hours of using the drug, peripheral vascular resistance increases slightly, and after 2-3 days it returns to the original level, and with prolonged use it decreases.

The hypotensive effect of the active component is due to a decrease in the minute amount of blood, a decrease in the function of the renin-angiotensin system , sympathetic activation of peripheral vessels, restoration of feedback when blood pressure decreases and an effect on the brain. For arterial hypertension, the effect occurs after 2-6 days, and a stable effect occurs only after about 2 months.

The antiarrhythmic effect is caused by the elimination of factors that provoke arrhythmia, as well as a decrease in the speed of spread of pacemaker excitation and a slowdown in AV conduction.

The antianginal effect is caused by a decrease in myocardial oxygen demand due to a decrease in heart rate and weakened contractility, improved perfusion of heart tissue, and prolongation of diastole. Due to increased diastolic pressure and stretching of the muscles of both ventricles, the need for oxygen may increase.

When used in therapeutic dosages, in contrast to non-selective beta-blockers, Cordinorm has a less strong effect on target organs (skeletal muscles, uterus, smooth muscles of arteries, pancreas, bronchi) and on carbohydrate metabolism, and does not cause sodium accumulation in the body. The strength of the atherogenic action is the same as that of Propranolol .

When used in large doses, it exhibits a blocking effect on both types of β-adrenergic receptors.

Pharmacokinetics

After taking the drug orally, up to 90% of bisoprolol . Food does not affect absorption. The highest plasma levels occur after 2-3 hours.

Interaction with blood proteins reaches approximately 35%. Permeability through histohematic barriers and the degree of excretion during lactation are low.

Half of the dose taken is transformed in the liver with the production of inactive derivatives.

The half-life is 11-12 hours. Up to 98% of the substance is excreted by the kidneys, another approximately 2% - with bile.

Cordinorm tablets ppo 5mg No. 90

Compound

1 tablet 5 mg contains:
active substance,

bisoprolol fumarate 5 mg,

Excipients:

microcrystalline cellulose 21.10 mg, mannitol 148.50 mg, croscarmellose sodium 1.80 mg, magnesium stearate 3.60 mg, hypromellose 2.19 mg, titanium dioxide 0.88 mg, macrogol 6000 0.53 mg.

1 tablet 10 mg contains:

active substance:

bisoprolol fumarate 10 mg,

Excipients:

microcrystalline cellulose 20.00 mg, mannitol 144.60 mg, croscarmellose sodium 1.80 mg, magnesium stearate 3.60 mg, hypromellose 2.19 mg, titanium dioxide 0.88 mg, macrogol 6000 0.53 mg.

Pharmacokinetics

Absorption - 80-90%, food intake does not affect absorption. The maximum concentration in blood plasma is observed after 1-3 hours, the connection with blood plasma proteins is about 35%. Permeability through the blood-brain barrier and placental barrier, secretion into breast milk is low. 50% of the dose is metabolized in the liver with the formation of inactive metabolites, the half-life is 9-12 hours. About 98% is excreted by the kidneys, 50% unchanged, less than 2% with bile.

Indications for use

- Arterial hypertension,

- coronary heart disease (prevention of angina attacks),

Contraindications

Symptoms:

arrhythmia, ventricular extrasystole, severe bradycardia, AV block, decreased blood pressure, chronic heart failure, cyanosis of fingernails or palms, difficulty breathing, bronchospasm, dizziness, fainting, convulsions.

Treatment:

gastric lavage and prescription of adsorbent drugs, symptomatic therapy: for developed AV blockade - intravenous (IV) 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 decrease Blood pressure - the patient should be in the Trendelenburg position, 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 a pronounced decrease in blood pressure), in case of heart failure - cardiac glycosides, diuretics , glucagon, for convulsions - intravenous diazepam, for bronchospasm - beta2-adrenergic stimulants by inhalation.

Directions for use and doses

Take orally, in the morning on an empty stomach, without chewing, 2.5-5 mg once. Usually the initial dose is 5 mg 1 time per day. If necessary, the dose is increased to 10 mg 1 time per day. The maximum dose for adults is 20 mg/day.

Treatment of arterial hypertension and angina pectoris

: Treatment of patients with mild or moderate hepatic or renal impairment usually does not require dose adjustment.

In patients with severe renal impairment (creatinine clearance less than 20 ml/min) or with severe liver dysfunction, the maximum daily dose is 10 mg.

No dose adjustment is required in elderly patients.

Storage conditions

At a temperature not exceeding 30 C.

Keep out of the reach of children.

Best before date

2 years.

Do not use after expiration date.

special instructions

Do not stop treatment abruptly or change the recommended dosage without first consulting your doctor.

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

The patient should be taught how to calculate heart rate and instructed about the need for medical consultation if the heart rate is less than 50 beats/min.

Before starting treatment, it is recommended to conduct a study of external respiratory function in patients with a burdened bronchopulmonary history.

In approximately 20% of patients with angina, beta blockers are ineffective. The main causes are severe coronary atherosclerosis with a low ischemic threshold (heart rate less than 100 beats/min) and increased end-diastolic volume of the left ventricle, impairing subendocardial blood flow.

Beta blockers are less effective in smokers.

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

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

In case of thyrotoxicosis, Cordinorm can mask certain clinical signs of thyrotoxicosis (for example, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated because it can increase symptoms.

In diabetes mellitus, it can mask tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, it practically does not enhance insulin-induced hypoglycemia and does not delay the restoration of blood glucose to normal levels.

When taking clonidine simultaneously, it can be discontinued only a few days after Cordinorm is discontinued.

It is possible that the severity of the hypersensitivity reaction may increase and there will be no effect from usual doses of epinephrine against the background of a burdened allergic history. If planned surgical treatment is necessary, the drug should be discontinued 48 hours before the start of general anesthesia. If the patient took the drug before surgery, he should choose a drug for general anesthesia with minimal negative inotropic effect.

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

Medicines that reduce the supply of catecholamines (for example, reserpine) may enhance the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision to detect arterial hypotension or bradycardia.

In case of increasing bradycardia (less than 50 beats/min), arterial hypotension (systolic blood pressure below 100 mm Hg), AV blockade, bronchospasm, ventricular arrhythmias, severe liver and kidney dysfunction in elderly patients, it is necessary to reduce the dose or stop treatment.

It is recommended to discontinue therapy if depression caused by taking beta-blockers develops.

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

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

Description

Round, convex, film-coated tablets, white, with a score on one side, side scores and engraving B 5 (for 5 mg tablets) or B 10 (for 10 mg tablets) on the other side.

Conditions for dispensing from pharmacies

On prescription

Dosage form

film-coated tablets

Pharmacodynamics

A selective beta1-blocker, without its own sympathomimetic activity, does not have a membrane-stabilizing effect. Reduces plasma renin activity, reduces myocardial oxygen demand, and reduces heart rate (heart rate) (at rest and during exercise). It has hypotensive, antiarrhythmic and antianginal effects. By blocking beta1-adrenergic receptors of the heart in low doses, it reduces the formation of cAMP from ATP stimulated by catecholamines, reduces the intracellular current of calcium ions, has a negative chrono-, dromo-, bathmo- and inotropic effect, inhibits conductivity and excitability, and slows down atrioventricular conduction.

With increasing dose, it has a beta2-adrenergic blocking effect.

The total peripheral vascular resistance at the beginning of the use of the drug, in the first 24 hours, increases slightly (as a result of a reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of stimulation of beta2-adrenergic receptors), which returns to the original level after 1-3 days, and decreases with long-term administration.

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

The antianginal effect is due to a decrease in myocardial oxygen demand as a result of a decrease in heart rate and decreased contractility, prolongation of diastole, and improved myocardial perfusion. By increasing end-diastolic pressure in the left ventricle and increasing the stretch of ventricular muscle fibers, it can increase oxygen demand, especially in patients with chronic heart failure.

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

Unlike non-selective beta-blockers, when prescribed in average therapeutic doses, it has a less pronounced effect on organs containing beta2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause Na+ retention in the body, the severity of the atherogenic effect does not differ from the effect of propranolol.

When used in large doses, it has a blocking effect on both subtypes of beta-adrenergic receptors.

Side effects

From the central nervous system:

increased fatigue, weakness, dizziness, headache, drowsiness or insomnia, nightmares, depression, anxiety, confusion or short-term memory loss, hallucinations, asthenia, myasthenia, paresthesia in the extremities (in patients with intermittent claudication and Raynaud's syndrome), tremor.

From the senses:

blurred vision, decreased secretion of tear fluid, dry and sore eyes, conjunctivitis.

From the cardiovascular system:

sinus bradycardia, palpitations, impaired myocardial conduction, impaired AV conduction (up to the development of complete transverse block and cardiac arrest), arrhythmias, weakened myocardial contractility, development (worsening) of chronic heart failure (swelling of the ankles, feet, shortness of breath), decreased blood pressure, orthostatic hypotension, manifestation of vasospasm (increased peripheral circulatory disorders, coldness of the lower extremities, Raynaud's syndrome), chest pain.

From the gastrointestinal tract:

dryness of the oral mucosa, nausea, vomiting, abdominal pain, constipation or diarrhea, liver dysfunction (dark urine, yellowness of the sclera or skin, cholestasis), changes in taste.

From the respiratory system,

nasal congestion, difficulty breathing when prescribed in high doses (loss of selectivity) and/or in predisposed patients - laryngo- and bronchospasm.

From the endocrine system:

hyperglycemia (in patients with non-insulin-dependent diabetes mellitus), hypoglycemia (in patients receiving insulin), hypothyroid state.

Allergic reactions:

skin itching, rash, urticaria.

From the skin:

increased sweating, skin hyperemia, exanthema, psoriasis-like skin reactions, exacerbation of psoriasis symptoms, alopecia.

Laboratory indicators

: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, changes in the activity of liver enzymes (increased ALT, AST), bilirubin levels, triglycerides.

Effect on the fetus:

intrauterine growth retardation, hypoglycemia, bradycardia.

From the musculoskeletal system:

muscle weakness, cramps in the calf muscles.

Other:

back pain, arthralgia, weakened libido, rarely - decreased potency, withdrawal syndrome (increased angina attacks, increased blood pressure).

Use during pregnancy and breastfeeding

Use during pregnancy and lactation is possible if the benefit to the mother outweighs the risk of side effects in the fetus and child.

Interaction

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

Iodine-containing radiocontrast drugs for intravenous administration increase the risk of anaphylactic reactions.

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

Changes the effectiveness of insulin and oral hypoglycemic drugs, masks the symptoms of developing hypoglycemia (tachycardia, increased blood pressure).

Reduces the clearance of lidocaine and xanthines (except diphylline) and increases their concentration in plasma, especially in patients with initially increased clearance of theophylline under the influence of smoking.

The hypotensive effect is weakened by nonsteroidal anti-inflammatory drugs (NSAIDs), sodium ion retention and blockade of prostaglandin synthesis by the kidneys), glucocorticosteroids and estrogens (Na+ retention).

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

Nifedipine can lead to a significant decrease in blood pressure.

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

Prolongs the effect of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins.

Tri- and tetracyclic antidepressants, antipsychotics (neuroleptics), ethanol, sedatives and hypnotics increase depression of the central nervous system.

Concomitant use with MAO inhibitors is not recommended due to a significant increase in the hypotensive effect; the break in treatment 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 plasma, rifampicin shortens the half-life.

Overdose

Symptoms:

Treatment:

Impact on the ability to drive vehicles and operate machinery

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Contraindications

Collapse.
Acute heart failure.
AV block above 2 degrees without the use of a pacemaker.
Prinzmetal's angina.
Shock.
Raynaud's disease.
Pulmonary edema.
Sinoatrial block.
Metabolic acidosis.
Weakness of the sinus node.
Chronic decompensated heart failure.
Severe bradycardia.
Cardiomegaly without symptoms characteristic of heart failure.
Arterial hypotension.
Joint use of MAO blockers.
Bronchial asthma or obstructive chronic pulmonary disease .
Late stages of peripheral circulatory disorders.
Pheochromocytoma (without the use of alpha-blockers ).
Hypersensitivity to the components of the drug or other beta-blockers.
Age up to 18 years.

It is recommended to use the drug with caution in myasthenia gravis, liver or kidney failure, diabetes mellitus, thyrotoxicosis, 1st degree AV block, psoriasis, depression, and elderly patients.

Overdose

Symptoms: arrhythmia, ventricular extrasystole, severe bradycardia, AV block, decreased blood pressure, chronic heart failure, cyanosis of fingernails or palms, 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 installation of a temporary pacemaker; for ventricular extrasystole - lidocaine (class Ia drugs are not used); when blood pressure decreases, the patient should be in the Trendelenburg position; 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 - beta2-adrenergic stimulants by inhalation.

Side effects

Disorders from the sensory organs: decreased secretion of tear fluid, blurred vision, soreness and dryness of the eyes, conjunctivitis .
Nervous system disorders: weakness, fatigue, dizziness , nightmares, sleep disorders, headache , depression, myasthenia gravis, confusion, memory loss, anxiety, asthenia , hallucinations , paresthesia, tremor.
Circulatory disorders: palpitations, decreased myocardial contractility, sinus bradycardia, changes in myocardial conductivity, arrhythmias , impaired AV conduction, progression of chronic heart failure, orthostatic hypotension , decreased pressure, manifestation of vasospasm, chest pain.
Respiratory disorders: respiratory distress, nasal congestion, laryngospasm or bronchospasm.
Digestive disorders: dry mouth, abdominal pain, vomiting, constipation or diarrhea , changes in taste, nausea, changes in liver function, changes in enzymes , triglycerides , bilirubin levels.
Hormonal disorders: hypoglycemia, hyperglycemia, hypothyroid state.
Dermatological reactions: redness of the skin, psoriasis-like reactions on the skin, increased sweating, exanthema, alopecia, exacerbation of psoriasis .
Allergic reactions : rash, urticaria , itching.
Hematopoietic disorders: agranulocytosis, leukopenia, thrombocytopenia.
Sexual disorders: weakened libido , decreased potency.
Disorders of the musculoskeletal system: muscle cramps in the legs, muscle weakness, arthralgia, lumbodynia.
Effect on the fetus: hypoglycemia , fetal growth restriction, bradycardia.
Other disorders: withdrawal syndrome.

Instructions for use of Cordinorm (Method and dosage)

Instructions for use of Cordinorm prescribe taking the medicine in the morning, on an empty stomach, orally, without chewing. A single dose is 2.5-5 mg. Typically the initial dose is 5 mg per day. If necessary, the dose is increased to 10 mg per day. The maximum daily dose is 20 mg.

Treatment of patients with compensated liver or kidney dysfunction usually does not require dose changes. In persons with severe renal dysfunction ( creatinine no more than 20 ml/min) or liver, the maximum daily dose is 10 mg.

In elderly people, there is no need to change the dose.

Interaction

In persons receiving bisoprolol , immunotherapeutic and diagnostic allergens, the risk of systemic severe allergic reactions .

Iodine-containing intravenous radiocontrast agents increase the risk of anaphylactic reactions.

When used simultaneously, bisoprolol can change the effectiveness of insulin and hypoglycemic agents , as well as mask the symptoms of emerging hypoglycemia.

Phenytoin, when administered intravenously and inhalational anesthetics, increases the strength of the cardiodepressive effect and the likelihood of lowering blood pressure.

When used together, bisoprolol reduces the clearance of xanthines and lidocaine , and also increases their content in the blood.

The hypotensive effect of the drug when used together is weakened by non-steroidal anti-inflammatory drugs, glucocorticosteroids and estrogens.

Cardiac glycosides, Reserpine, Methyldopa, Guanfacine, slow calcium channel inhibitors, Amiodarone and other antiarrhythmic drugs, when used simultaneously with bisoprolol , increase the risk of developing AV block, bradycardia and even cardiac arrest.

When used together, Nifedipine can significantly reduce blood pressure.

Diuretics, Clonidine, sympatholytics, Hydralazine and other antihypertensive drugs when used together can cause an excessive decrease in blood pressure.

Cordinorm increases the duration of action of non-depolarizing muscle relaxants and coumarins.

and tetracyclic antidepressants and hypnotics enhance the suppressive effect of bisoprolol on nervous function.

Concomitant use with MAO blockers (as well as the use of Cordinorm within a two-week period after taking them) is not recommended due to the increased hypotensive effect.

Ergotamine, when used simultaneously, increases the risk of developing peripheral circulatory disorders.

Non-hydrogenated ergot alkaloids, when used together, increase the risk of peripheral circulatory disorders.

Rifampicin, when used together, shortens the half-life of the active component.

Sulfasalazine increases the level of bisoprolol in the blood.

Cordinorm film-coated tablets 5 mg No. 30

Cordinorm film-coated tablets 5 mg No. 30
Pharmacological action
Selective beta1-blocker without internal sympathomimetic activity and membrane-stabilizing properties. By blocking β1-adrenergic receptors of the heart in low doses, bisoprolol reduces the formation of cAMP from ATP stimulated by catecholamines and reduces the intracellular current of calcium ions. It has a negative chrono-, dromo-, bathmo- and inotropic effect, inhibits conductivity and excitability, slows down AV conduction, and reduces myocardial oxygen demand. Reduces heart rate at rest and during exercise. Reduces plasma renin activity. It has hypotensive, antiarrhythmic and antianginal effects.

As the dose increases, bisoprolol has a beta2-adrenergic blocking effect.

At the beginning of drug use (in the first 24 hours), as a result of a reciprocal increase in the activity of α-adrenergic receptors and the elimination of stimulation of β2-adrenergic receptors, OPSS increases slightly. After 1-3 days, OPSS returns to the initial level, and with long-term use it decreases.

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

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

Unlike non-selective beta-blockers, when prescribed in average therapeutic doses, bisoprolol 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 sodium retention in organism. The severity of the atherogenic effect does not differ from the effect of propranolol.

When used in large doses, it has a blocking effect on both subtypes of β-adrenergic receptors.

Pharmacokinetics

Suction

After taking the drug orally, 80-90% of bisoprolol is absorbed from the gastrointestinal tract. Taking with food does not affect absorption. Cmax in blood plasma is achieved after 1-3 hours.

Distribution

Binding to blood plasma proteins is about 35%. Permeability through the BBB and placental barrier, as well as the degree of penetration into breast milk, is low.

Metabolism and excretion

50% of the dose taken is metabolized in the liver with the formation of inactive metabolites. 50% is displayed unchanged.

T1/2 is 9-12 hours. About 98% of the substance is excreted by the kidneys, less than 2% - with bile.
Indications for use of the drug CORDINORM
: arterial hypertension;

— IHD (prevention of angina attacks).
Dosage regimen:
A single dose is 2.5-5 mg. Usually the initial dose is 5 mg 1 time / day. If necessary, the dose is increased to 10 mg 1 time / day. The maximum daily dose for adults is 20 mg.

The tablets should be taken orally, in the morning, on an empty stomach, without chewing.

Treatment of
mild or moderate
hepatic or renal impairment usually does not require dose adjustment.
In patients with severe renal impairment (creatinine clearance <20 ml/min) or liver
, the maximum daily dose is 10 mg.

In
elderly
patients, no dose adjustment is required.
Side effects
From the central nervous system: increased fatigue, weakness, dizziness, headache, drowsiness or insomnia, nightmares, depression, anxiety, confusion or short-term memory loss, hallucinations, asthenia, myasthenia, paresthesia in the extremities (in patients with intermittent claudication and Raynaud's syndrome), tremor.

From the senses: blurred vision, decreased secretion of tear fluid, dry and sore eyes, conjunctivitis.

From the cardiovascular system: sinus bradycardia, palpitations, impaired myocardial conduction, impaired AV conduction (up to the development of complete transverse block and cardiac arrest), arrhythmias, weakened myocardial contractility, development (worsening) of chronic heart failure (swelling of the ankles, feet ; shortness of breath), decreased blood pressure, orthostatic hypotension, manifestation of vasospasm (increased peripheral circulatory disorders, coldness of the lower extremities, Raynaud's syndrome), chest pain.

From the digestive system: dryness of the oral mucosa, nausea, vomiting, abdominal pain, constipation or diarrhea, liver dysfunction (dark urine, yellowness of the sclera or skin, cholestasis), changes in the activity of liver enzymes (increased ALT, AST), levels bilirubin, triglycerides, taste changes.

From the respiratory system: nasal congestion, difficulty breathing when prescribed in high doses (due to loss of selectivity) and/or in predisposed patients - laryngo- and bronchospasm.

From the endocrine system: hyperglycemia (in patients with non-insulin-dependent diabetes mellitus), hypoglycemia (in patients receiving insulin), hypothyroid state.

Dermatological reactions: increased sweating, skin hyperemia, exanthema, psoriasis-like skin reactions, exacerbation of psoriasis symptoms, alopecia.

From the hematopoietic system: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia.

From the musculoskeletal system: muscle weakness, cramps in the calf muscles, back pain, arthralgia.

From the reproductive system: weakened libido and decreased potency.

Allergic reactions: skin itching, rash, urticaria.

Other: withdrawal syndrome (increased angina attacks, increased blood pressure).

Effect on the fetus: intrauterine growth retardation, hypoglycemia, bradycardia.

Contraindications
for the use of the drug CORDINORM
are shock (including cardiogenic);

- collapse;

- pulmonary edema;

- acute heart failure;

— chronic heart failure in the stage of decompensation;

— AV blockade of II and III degrees (without pacemaker);

- sinoatrial block;

— SSSU;

— severe bradycardia (heart rate <50 beats/min);

- Prinzmetal's angina;

- cardiomegaly (without signs of heart failure);

- arterial hypotension (systolic blood pressure <100 mm Hg, especially with myocardial infarction);

- history of bronchial asthma and COPD;

- simultaneous use of MAO inhibitors (with the exception of MAO type B);

— late stages of peripheral circulatory disorders;

- Raynaud's disease;

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

- metabolic acidosis;

- children and adolescents under 18 years of age (efficacy and safety of use have not been established);

- increased sensitivity to other beta-blockers;

- hypersensitivity to the components of the drug.

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

Use of the drug CORDINORM during pregnancy and lactation

Use during pregnancy and lactation is possible if the potential benefit to the mother outweighs the risk of side effects in the fetus and child (such as intrauterine growth retardation, hypoglycemia, bradycardia).

Use for liver dysfunction

Treatment of patients with mild or moderate hepatic impairment usually does not require dose adjustment. In patients with severe liver dysfunction, the maximum daily dose should not exceed 10 mg.

Use for renal impairment

Treatment of patients with mild or moderate renal impairment usually does not require dose adjustment.
In patients with severe renal impairment (creatinine clearance less than 20 ml/min.), the maximum daily dose should not exceed 10 mg. Special instructions
The patient should be aware that they should not abruptly interrupt treatment or change the recommended dose without first consulting a doctor.

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

The patient should be taught how to calculate heart rate and instructed about the need for medical consultation if the heart rate is less than 50 beats/min.

Before starting treatment in patients with a complicated bronchopulmonary history, it is recommended to conduct a study of external respiratory function.

In approximately 20% of patients with angina, beta blockers are ineffective. The main reasons for this are severe coronary atherosclerosis with a low ischemic threshold (heart rate less than 100 beats/min) and increased end-diastolic volume of the left ventricle, which impairs subendocardial blood flow.

When smoking, the effectiveness of beta-blockers is lower.

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

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

In patients with thyrotoxicosis, Cordinorm may mask certain clinical signs of thyrotoxicosis (for example, tachycardia). Abrupt withdrawal of the drug in patients with thyrotoxicosis is contraindicated, as it can increase symptoms.

In diabetes mellitus, the effect of bisoprolol may mask tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, Cordinorm practically does not enhance insulin-induced hypoglycemia and does not delay the restoration of blood glucose to normal levels.

With simultaneous treatment with clonidine, its use can be discontinued only a few days after discontinuation of Cordinorm .

It is possible that the severity of the hypersensitivity reaction may increase and there will be no effect from the usual doses of epinephrine (adrenaline) against the background of a burdened allergological history. If planned surgical treatment is necessary, the drug should be discontinued 48 hours before the start of general anesthesia. If the patient took the drug before surgery, he should choose a drug for general anesthesia with minimal negative inotropic effect.

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

Patients with bronchospastic diseases can be prescribed cardioselective adrenergic blockers in case of intolerance and/or ineffectiveness of other antihypertensive drugs, but the dose should be strictly controlled. An overdose is dangerous due to the development of bronchospasm. In case of increasing bradycardia (less than 50 beats/min), arterial hypotension (systolic blood pressure below 100 mm Hg), AV blockade, bronchospasm, ventricular arrhythmias, severe liver and kidney dysfunction in elderly patients, it is necessary to reduce the dose or stop treatment.

It is recommended to discontinue therapy if depression caused by taking beta-blockers develops.

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

Impact on the ability to drive vehicles and operate machinery

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Treatment: gastric lavage and administration of adsorbent drugs;
symptomatic therapy: for developed AV block - intravenous administration of 1-2 mg of atropine, epinephrine (adrenaline) or installation of a temporary pacemaker; for ventricular extrasystole - administration of lidocaine (class IA drugs are not used); when blood pressure decreases, the patient should be in the Trendelenburg position; if there are no signs of pulmonary edema, plasma-substituting solutions should be administered intravenously; if ineffective, epinephrine (adrenaline), dopamine, dobutamine should be administered (to maintain the chronotropic and inotropic effects and eliminate the pronounced decrease in blood pressure); for heart failure - administration of cardiac glycosides, diuretics, glucagon; for convulsions - intravenous administration of diazepam; for bronchospasm - inhaled beta2-adrenergic stimulants. Drug Interactions
In patients receiving bisoprolol, allergens used for immunotherapy or allergen extracts for skin testing increase the risk of severe systemic allergic reactions or anaphylaxis.

Iodine-containing radiopaque drugs for intravenous administration increase the risk of developing anaphylactic reactions.

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

When used together, bisoprolol changes the effectiveness of insulin and oral hypoglycemic agents, masks the symptoms of developing hypoglycemia (tachycardia, increased blood pressure).

With simultaneous use, bisoprolol reduces the clearance of lidocaine and xanthines (except diphylline) and increases their concentration in plasma, especially in patients with initially increased clearance of theophylline under the influence of smoking.

The hypotensive effect of the drug when used together is weakened by NSAIDs (due to the retention of sodium ions and blockade of prostaglandin synthesis by the kidneys), corticosteroids and estrogens (due to the retention of sodium ions).

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

With simultaneous use, nifedipine can lead to a significant decrease in blood pressure.

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

Cordinorm prolongs the effect of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins.

Tricyclic and tetracyclic antidepressants, antipsychotics (neuroleptics), ethanol, sedatives and hypnotics enhance the inhibitory effect of bisoprolol on the central nervous system.

Non-hydrogenated ergot alkaloids, when used together, increase the risk of developing peripheral circulatory disorders.

When used together, ergotamine increases the risk of developing peripheral circulatory disorders.

Sulfasalazine increases the concentration of bisoprolol in plasma.

Rifampicin, when used simultaneously, shortens the T1/2 half of bisoprolol.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Storage conditions and periods

The drug should be stored out of the reach of children at a temperature not exceeding 30°C. Shelf life: 2 years.
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special instructions

It is not recommended to suddenly stop treatment or change the recommended dose without consulting your doctor.

Monitoring of persons taking Cordinorm includes monitoring heartbeat and blood pressure levels, conducting an ECG , and testing glucose in patients with diabetes (once every 4 months). In elderly patients, it is recommended to monitor kidney function (every 4 months).

Before starting treatment in patients with a significant pulmonary history, it is necessary to conduct an external respiration study.

In approximately 20% of patients suffering from angina , beta blockers are ineffective.

When smoking, the effects of beta-blockers are weakened.

When using Cordinorm in people with pheochromocytoma , there is a risk of developing arterial hypertension of the paradoxical type.

Increased hypersensitivity reactions and ineffectiveness of usual dosages of Epinephrine in case of a burdened allergic history. If surgical treatment is necessary, discontinuation of the drug is carried out two days before the start of anesthesia.

Medicines that reduce catecholamine can stimulate the effect of beta-blockers , therefore, patients taking these combinations of drugs should be under regular medical supervision.

Persons with bronchospastic diseases are allowed to prescribe selective adrenergic blockers if other antihypertensive drugs , but the dosage must be strictly controlled. An overdose may cause bronchospasm.

It is recommended to discontinue therapy if depression caused by the use of beta blockers .

It is forbidden to abruptly interrupt therapy due to the risk of myocardial infarction and life-threatening arrhythmias .

Cancellation is carried out gradually, reducing the dose over 2 weeks or more.

During therapy, patients need to be careful when driving.

Pharmacodynamics

Selective beta1-blocker without its own sympathomimetic activity. By blocking beta1-adrenergic receptors of the heart in low doses, it reduces the catecholamine-stimulated formation of cAMP from ATP, reduces the intracellular Ca2+ current, has a negative chrono-, dromo-, bathmo- and inotropic effect (reduces heart rate, inhibits conductivity and excitability, reduces myocardial contractility). With increasing dose, it has a beta2-adrenergic blocking effect. OPSS at the beginning of the use of beta-adrenergic blockers, in the first 24 hours, increases (as a result of a reciprocal increase in the activity of alpha-adrenergic receptors and the elimination of stimulation of beta2-adrenergic receptors), which after 1-3 days returns to the original level, and with long-term administration decreases.

The hypotensive effect is associated with a decrease in IOC, sympathetic stimulation of peripheral vessels, a decrease in the activity of the renin-angiotensin system (of greater importance for patients with initial hypersecretion of renin), restoration of the sensitivity of the baroreceptors of the aortic arch (there is no increase in their activity in response to a decrease in blood pressure) and an effect on CNS. In case of arterial hypertension, the effect occurs after 2–5 days, stable effect occurs after 1–2 months. The antianginal effect is due to a decrease in myocardial oxygen demand as a result of a decrease in heart rate and decreased contractility, prolongation of diastole, and improved myocardial perfusion. By increasing the final dBP in the left ventricle and increasing the stretching of the ventricular muscle fibers, it can increase the need for oxygen, especially in patients with chronic heart failure. The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP content, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and a slowdown of AV conduction (mainly in the anterograde and to a lesser extent in the retrograde directions through the AV node) and along additional paths. In contrast to non-selective beta-blockers, when prescribed in average therapeutic doses, it has a less pronounced effect on organs containing beta2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause Na + retention in organism; the severity of the atherogenic effect does not differ from the effect of propranolol. When used in large doses, it has a blocking effect on both subtypes of beta-adrenergic receptors.

Analogs

Level 4 ATC code matches:
Biol

Metocard

Metozok

Nebilet

Nebilong

Betaxolol

Bisogamma

Aritel

Vasocardin

Corvitol

Bidop

Bisoprolol

Nebivolol

Biprol

Bisoprol

Concor Cor

Lokren

Concor

Niperten

Betaloc ZOK

Analogues of Cordinorm: Aritel, Bidop, Aritel Cor, Biol, Coronal, Bisogamma, Niperten, Bisocard, Concor, Bisomore, Biprol, Bisoprolol, Corbis, Bisoprolol-Teva, Bisoprolol-OBL, Tirez.