Coronal tablets p / o 5mg, No. 100

arterial hypertension;

IHD: prevention of angina attacks.

KOPOHALЃ is taken orally, in the morning on an empty stomach, without chewing, with a small amount of liquid.
With arterial hypertension and ischemic heart disease (prevention of attacks of stable angina pectoris), the initial dose is 2.5 - 5 mg once a day. If necessary, the dose is increased to 10 mg once a day. The maximum daily dose is 20 mg / day. In patients with impaired renal function with creatinine clearance less than 20 ml / min or with severe impaired liver function, the maximum daily dose is 10 mg.
No dose adjustment is required in elderly patients.

film-coated tablets.

Each film-coated tablet contains:

active substance

Bisoprolol fumarate 5.0 mg / 10.0 mg

Excipients

core:

Microcrystalline cellulose 133.0 mg / 128.0 mg

Corn starch 7.50 mg / 7.50 mg

Sodium lauryl sulfate 1.0 mg / 1.0 mg

Colloidal silicon dioxide 2.0 mg / 2.0 mg

Magnesium stearate 1.50 mg / 1.50 mg

film casing:

Hypromellose 6.40 mg / 6.40 mg

Macrogol 400 - 1.28 mg / 1.28 mg

Titanium dioxide 2.30 mg / 2.30 mg

Iron dye yellow oxide (E 172) - 0.02 mg (for a dosage of 5 mg)

Iron dye oxide red (E 172) - 0.02 mg (for a dosage of 10 mg)

Hypersensitivity to the components of the drug and other beta-blockers, shock (including cardiogenic), acute heart failure, chronic heart failure in the stage of decompensation, AV block II-III degree (without an artificial pacemaker), sinoatrial block, sick sinus syndrome , severe bradycardia, cardiomegaly (without signs of heart failure), arterial hypotension (systolic blood pressure less than 100 mm Hg, especially with myocardial infarction); history of bronchial asthma and chronic obstructive pulmonary disease; concomitant use of monoamine oxidase (MAO) inhibitors (except for MAO type B inhibitors), concomitant use of floctaphenin and sultopride, late stages of peripheral circulatory disorders, Raynaud's disease, lactation period,age up to 18 years (efficacy and safety have not been established).

Trade name of the drug: CORONAL

International non-proprietary name:

bisoprolol

Dosage form:

film-coated tablets.

Each film-coated tablet contains:

active substance

Bisoprolol fumarate 5.0 mg / 10.0 mg

Excipients

core:

Microcrystalline cellulose 133.0 mg / 128.0 mg

Corn starch 7.50 mg / 7.50 mg

Sodium lauryl sulfate 1.0 mg / 1.0 mg

Colloidal silicon dioxide 2.0 mg / 2.0 mg

Magnesium stearate 1.50 mg / 1.50 mg

film casing:

Hypromellose 6.40 mg / 6.40 mg

Macrogol 400 - 1.28 mg / 1.28 mg

Titanium dioxide 2.30 mg / 2.30 mg

Iron dye yellow oxide (E 172) - 0.02 mg (for a dosage of 5 mg)

Iron dye oxide red (E 172) - 0.02 mg (for a dosage of 10 mg)

Description
Tablets 5 mg: round, biconvex, light yellow, scored film-coated tablets.
Tablets 10 mg: round, biconvex, light pink, scored film-coated tablets.

Pharmacotherapeutic group:

beta1-blocker selective.

Pharmacological action
Pharmacodynamics
Selective beta1-blocker, has a slight membrane stabilizing effect and a slight internal sympathomimetic activity. Reduces plasma renin activity, reduces myocardial oxygen demand, reduces heart rate (HR) (at rest and during exercise). It has antihypertensive, antiarrhythmic and antianginal effects. Blocking in low doses beta 1 -adrenergic receptors of the heart, reduces the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP) stimulated by catecholamines, reduces the intracellular flow of calcium ions, has a negative chrono-, dromo-, batmo- and inotropic effect (slows down the heart rate inhibits conductivity and excitability, reduces myocardial contractility). With an increase in the dose, it has a beta2-adrenergic blocking effect.
The total peripheral vascular resistance (OPSR) at the beginning of drug use, in the first 24 hours after oral administration, increases (as a result of a reciprocal increase in the activity of alpha-adrenergic receptors and elimination of stimulation of beta2-adrenergic receptors), which returns to the initial value after 1-3 days, and long-term appointment is reduced.
The antihypertensive effect is associated with a decrease in the minute volume of blood, sympathetic stimulation of peripheral vessels, a decrease in the activity of the renin-angiotensin-aldosterone system (it is of great importance for patients with initial hypersecretion of renin), and the central nervous system (CNS), restoration of the sensitivity of the baroreceptors of the aortic arch (does not occur an increase in their activity in response to a decrease in blood pressure (BP)) and, as a result, a decrease in peripheral sympathetic influences. With arterial hypertension, the effect occurs after 2-5 days, a stable effect - 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, a decrease in contractility, an increase in diastole, an improvement in myocardial perfusion, and a decrease in the sensitivity of the myocardium to the effects of sympathetic innervation. Reduces the number and severity of angina attacks and increases exercise tolerance. Due to an increase in the end diastolic pressure in the left ventricle and an increase in the stretching of the muscle fibers of the ventricles, oxygen demand can increase, especially in patients with chronic heart failure (CHF).
The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased content of cyclic adenosine monophosphate, arterial hypotension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and a slowdown in artoventricular (AV) conduction (mainly in antegrade and, to a lesser extent) in retrograde directions through the AV node) and along additional paths.
When used in moderate therapeutic doses, in contrast to non-selective beta-blockers, 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 delay sodium ions (Na +) in the body; the severity of atherogenic action does not differ from the action of propranolol. When used in large doses (200 mg or more), it has a blocking effect on both subtypes of beta-adrenergic receptors, mainly in the bronchi and vascular smooth muscles.
Pharmacokinetics
Absorption - 80 - 90%, food intake does not affect absorption. The maximum concentration in blood plasma is observed after 1 to 3 hours, the connection with blood plasma proteins is about 30%.
Permeability through the blood-brain barrier and placental barrier is low, secretion in breast milk is low.
It is metabolized in the liver with the formation of inactive metabolites, the half-life is 10-12 hours. About 98% is excreted by the kidneys, of which 50% are excreted unchanged, less than 2% with bile.

Indications for use
- arterial hypertension;
- ischemic heart disease: prevention of angina attacks.

Contraindications for use
Hypersensitivity to the components of the drug and other beta-blockers, shock (including cardiogenic), acute heart failure, chronic heart failure in the stage of decompensation, AV block II-III degree (without an artificial pacemaker), sinoatrial block, sick sinus syndrome , severe bradycardia, cardiomegaly (without signs of heart failure), arterial hypotension (systolic blood pressure less than 100 mm Hg, especially with myocardial infarction); history of bronchial asthma and chronic obstructive pulmonary disease; concomitant use of monoamine oxidase (MAO) inhibitors (except for MAO type B inhibitors), concomitant use of floctaphenin and sultopride, late stages of peripheral circulatory disorders, Raynaud's disease, lactation period,age up to 18 years (efficacy and safety have not been established).

Method of application and doses
KOPOHALЃ is taken orally, in the morning on an empty stomach, without chewing, with a small amount of liquid.
With arterial hypertension and coronary heart disease (prevention of attacks of stable angina pectoris), the initial dose is 2.5 - 5 mg once a day. If necessary, the dose is increased to 10 mg once a day. The maximum daily dose is 20 mg / day. In patients with impaired renal function with creatinine clearance less than 20 ml / min or with severe impaired liver function, the maximum daily dose is 10 mg.
No dose adjustment is required in elderly patients.

Precautions for use
Liver failure, renal failure (creatinine clearance less than 20 ml / min), metabolic acidosis, pheochromocytoma (with the concomitant use of alpha-blockers), diabetes mellitus in the stage of decompensation, atrioventricular block of the I degree, angina pectoris in Prinzmetal cardiac, restrictive heart defects or heart valve defects with severe hemodynamic disorders, chronic heart failure with myocardial infarction within the last 3 months, psoriasis, depression (including a history), a history of severe allergic reactions, pregnancy, old age, strict diet, desensitizing immunotherapy with allergens and allergen extracts.

Overdose
Symptoms: arrhythmia, ventricular premature beats, severe bradycardia, AV block, marked decrease in blood pressure, acute heart failure, acrocyanosis, difficulty breathing, bronchospasm, dizziness, fainting, convulsions.
Treatment:gastric lavage and the appointment of adsorbent drugs; symptomatic therapy: with developed AV blockade - intravenous (i / v) 1-2 mg of atropine, epinephrine or setting a temporary pacemaker; with ventricular premature beats - lidocaine (class Ia drugs are not used); with a decrease in blood pressure - the patient should be in the Trendelnburg position; if there are no signs of pulmonary edema - intravenous plasma-substituting solutions, if ineffective - the introduction of epinephrine, dopamine, dobutamine (to maintain chronotropic and ionotropic action and eliminate a pronounced decrease in blood pressure); with heart failure - cardiac glycosides, diuretics, glucagon; for convulsions - intravenous diazepam; with bronchospasm - inhalation beta2-adrenostimulants.

Peculiarities of the action of the drug at the first admission or at its cancellation
Do not abruptly interrupt the treatment because of the danger of the development of the 'withdrawal' syndrome (severe arrhythmias and myocardial infarction). Cancellation is carried out gradually, reducing the dose for 2 weeks or more (reduce the dose by 25% in 3-4 days).

Side effect
Frequency: very often (more than or equal to 1/10); often (more than 1/100, less than 1/10); infrequently (more than 1/1000, less than 1/100); rarely (more than 1/10000, less than 1/1000); very rare (less than 1/10000, including individual messages).
From the side of the central nervous system: infrequently - increased fatigue, asthenia, dizziness, headache, drowsiness or insomnia, depression, rarely hallucinations, nightmares, convulsions.
From the senses: rarely - visual impairment, decreased secretion of lacrimal fluid, dryness and soreness of the eyes, hearing impairment; very rarely - conjunctivitis.
On the part of the cardiovascular system:very often - sinus bradycardia, often - a decrease in blood pressure, manifestation of angiospasm (increased disturbance of peripheral circulation, coldness of the lower extremities, paresthesia), infrequently - violation of artioventricular conduction, orthostatic hypotension, decompensation of chronic heart failure, peripheral edema.
From the digestive system: often - dryness of the oral mucosa, nausea, vomiting, diarrhea, constipation, rarely - hepatitis.
On the part of the respiratory system: infrequently - difficulty in breathing when administered in high doses (loss of selectivity) and / or in predisposed patients - laryngo- and bronchospasm; rarely - nasal congestion, allergic rhinitis.
From the endocrine system:rarely - hyperglycemia (in patients with type 2 diabetes mellitus), hypoglycemia (in patients receiving insulin.
Allergic reactions: rarely - skin itching, rash, urticaria.
On the part of the skin: rarely - increased sweating, skin flushing, very rarely - psoriasis-like skin reactions, exacerbation of psoriasis symptoms, alopecia
From the musculoskeletal system: infrequently - muscle weakness, cramps in the calf muscles, arthralgia
Laboratory indicators: rarely - increased activity of 'hepatic' transaminases, hypertriglyceridemia, in some cases - thrombocytopenia, agranulocytosis.
Effect on the fetus: intrauterine growth retardation, hypoglycemia, bradycardia.
Other: very rarely - violation of potency, rarely - 'withdrawal' syndrome (increased angina attacks, increased blood pressure).

Interaction with other medicinal products
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 X-ray contrast drugs for intravenous administration increase the risk of anaphylactic reactions.
Intravenous phenytoin, drugs for inhalation anesthesia (hydrocarbon derivatives) increase the severity of the cardiodepressant effect and the likelihood of lowering blood pressure.
Changes the effectiveness of insulin and hypoglycemic agents for oral administration, masks the symptoms of developing hypoglycemia (tachycardia, increased blood pressure). Reduces the clearance of lidocaine and xanthines (except diphylline) and increases their plasma concentration, especially in patients with an initially increased clearance of theophylline under the influence of smoking.
The antihypertensive effect is weakened by non-steroidal anti-inflammatory drugs (retention of sodium ions (Na +) and blockade of prostaglandin synthesis by the kidneys), glucocorticosteroids and estrogens (retention of sodium ions).
Cardiac glycosides, methyldopa, reserpine and guanfacine, blockers of 'slow' calcium channels (verapamil, diltiazem), amiodarone and other antiarrhythmic drugs increase the risk of developing or worsening bradycardia, AV blockade, 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.
It lengthens the action of non-depolarizing muscle relaxants and increases the anticoagulant effect of coumarins.
Tri- and tetracyclic antidepressants, antipsychotics (antipsychotics, including sultopride), ethanol, sedatives and hypnotics increase the depression of the central nervous system, can provoke cardiac arrhythmias, bradycardia and orthostatic hypotension.
Simultaneous use with monoamine oxidase inhibitors is not recommended, due to a significant increase in the antihypertensive effect, the break in treatment between taking monoamine oxidase inhibitors and bisoprolol should be at least 14 days.
Unhydrogenated ergot alkaloids increase the risk of developing peripheral circulatory disorders.
Ergotamine increases the risk of developing peripheral circulatory disorders; sulfasalazine increases the plasma concentration of bisoprolol; rifampicin shortens the half-life of the drug.
There is a potential danger of an additive effect with the development of hypotension and / or significant bradycardia, when used together with topical beta-blockers (eye drops).
There is a decrease in the antihypertensive effect of the drug against the background of the use of adrenaline and norepinephrine.
The likelihood of violations of automatism, conduction and contractility of the heart increases (mutually) against the background of therapy with quinidine drugs (mefloquine, chloroquine).
In case of shock or arterial hypotension caused by floktaphenin, when used together, it is possible to reduce compensatory cardiovascular reactions.
With simultaneous use with baclofen or amifostine, an increase in the antihypertensive effect is also noted.

Features of use by pregnant women, women during breastfeeding, children, adults with chronic diseases
During pregnancy, CORONAL is prescribed only under strict indications if the intended benefit to the mother outweighs the potential risk to the fetus. 72 hours before childbirth, taking the drug CORONAL should be discontinued due to the possible development of bradycardia, arterial hypotension, hypoglycemia and respiratory depression in the fetus / newborn.
If taking CORONAL is necessary during lactation, breastfeeding should be discontinued.
The use of the drug CORONAL in children under 18 years of age is contraindicated, since the efficacy and safety have not been established.
Monitoring patients taking CORONAL should include measuring heart rate and blood pressure (at the beginning of treatment - daily, then once every 3-4 months), electrocardiogram, determination of blood glucose concentration in patients with diabetes mellitus (1 time in 4 -5 months). In elderly patients, it is recommended to monitor kidney function (once every 4-5 months).
The patient should be trained in the method of calculating the heart rate and instructed on the need for medical advice when the heart rate is less than 50 beats / min.
Before starting treatment, it is recommended to conduct a study of the function of external respiration in patients with a burdened bronchopulmonary history.
Beta-blockers are ineffective in about 20% of patients with angina pectoris. The main causes are severe coronary atherosclerosis with a low ischemic threshold (heart rate less than 100 beats / min) and an increased left ventricular end-diastolic volume, which disrupts subendocardial blood flow.
For 'smokers' the effectiveness of beta-blockers is lower.
Patients using contact lenses should take into account that during treatment, it is possible to reduce the production of tear fluid.
When used in patients with pheochrocytoma, there is a risk of developing paradoxical arterial hypertension (if an effective alpha-blockade is not previously achieved).
With thyrotoxicosis, bisoprolol can mask certain clinical signs of threotoxicosis (for example, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, since it can increase the symptoms.
In diabetes mellitus, it can mask tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, it practically does not increase insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentration to normal levels.
If you are taking clonidine at the same time, you can stop taking it only a few days after stopping the drug CORONAL.
It is possible that the severity of the hypersensitivity reaction and the lack of effect from the usual doses of epinephrine against the background of a burdened allergic history are possible. If it is necessary to carry out planned surgical treatment, the drug is 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 administration of atropine (1Ц2 mg).
Medicines that reduce the supply of catecholamines (including reserpine) can enhance the action of beta-blockers, therefore, patients taking such combinations of medicines should be under constant medical supervision to detect a pronounced decrease in blood pressure or bradycardia.
Patients with bronchospastic diseases can be prescribed cardioselective beta-blockers in case of intolerance and / or ineffectiveness of other antihypertensive drugs. Overdose is dangerous for the development of bronchospasm. If elderly patients develop an increasing bradycardia (less than 50 beats / min), a pronounced decrease in blood pressure (systolic blood pressure below 100 mm Hg), AV blockade, it is necessary to reduce the dose or stop treatment.
It is recommended to discontinue therapy if depression develops.
The drug should be discontinued before examining the content of catecholamines, normetanephrine, and vanillin mandelic acid in the blood and urine; antinuclear antibody titers.

Influence on the ability to drive vehicles and mechanisms
During the period of treatment, care must be taken when driving a vehicle and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Release form
Film-coated tablets 5 mg, 10 mg.
10 tablets in a blister of PVC / PE / PVDC-AL or in a blister of A1 / A1. 1, 3, 6 or 10 blisters, together with instructions for use, are placed in a cardboard box.

Shelf life
2 years
The drug should not be used after the expiration date indicated on the package.

Terms of dispensing from pharmacies
Prescription.

Storage conditions
At a temperature not exceeding 25 ? —.
Keep out of the reach of children.