Koronal

General characteristics. Structure:

Each tablet film coated contains:
                                                    5        mg 10 mg
active agent
Bisoprolola fumarates                   5,0     mg 10,0 mg
excipients
kernel:
Cellulose of microcrystallic 133,0 mg 128,0 mg
Starch of corn                      7,50   mg 7,50 mg
Sodium lauryl sulfate                  of 1,0     mg 1,0 mg
Silicon dioxide of colloid       2,0     mg 2,0 mg
Magnesium stearate                             of 1,50   mg 1,50 mg
film cover:
Gipromelloza                               of 6,40   mg 6,40 mg
Macrogoal of 400                               1,28   mg 1,28 mg
Titanium dioxide                            of 2,30    mg 2,30 mg
Dye Ferrous oxide
 yellow (Е 172)                            0,02 mg      -
Dye Ferrous oxide
 red (Е 172)                             -            0,02 mg

Description
Tablets of 5 mg: round biconvex tablets of light yellow color with risky, film coated.
Tablets of 10 mg: round biconvex tablets of light pink color with risky, film coated.

Pharmacological properties:

Pharmacodynamics. The selection beta1-adrenoblocker, possesses insignificant membrane stabilizing action and insignificant internal sympathomimetic activity. Reduces activity of a renin of plasma, reduces the need of a myocardium for oxygen, reduces the heart rate (HR) (at rest and at loading). Has anti-hypertensive, antiarrhytmic and anti-anginal effect. Blocking in low doses a beta 1 - heart adrenoceptors, reduces stimulated catecholamines formation of cyclic adenosinemonophosphate (tsAMF) from adenosinetriphosphate (ATP), reduces intracellular current of calcium ions, renders negative hrono-, dromo-, batmo-and inotropic action (urezhat heart rate, conductivity and excitability oppresses, reduces contractility of a myocardium). At increase in a dose has beta2-adrenoceptor blocking effect.
The General Peripheric Vascular Resistance (GPVR) at the beginning of drug use, in the first 24 h after intake, increases (as a result of reciprocal increase of activity of alpha adrenoceptors and elimination of stimulation of beta2-adrenoceptors) which in 1-3 days is returned to initial, and at long appointment decreases.
Anti-hypertensive action is connected with reduction of minute volume of blood, sympathetic stimulation of peripheral vessels, decrease of the activity system renin-angiotensin-aldosteronovoy (is of great importance for patients with initial hypersecretion of a renin), and the central nervous system (CNS), recovery of sensitivity of baroreceptors of an aortic arch (there is no strengthening of their activity in response to a lowering of arterial pressure (ABP)) and as a result reduction of peripheral sympathetic influences. At arterial hypertension the effect occurs in 2-5 days, stable action - in 1-2 months.
The anti-anginal effect is caused by reduction of need of a myocardium for oxygen as a result of an urezheniye of heart rate, decrease in contractility, lengthening of a diastole, improvement of perfusion of a myocardium, and also decrease in sensitivity of a myocardium to influence of a sympathetic innervation. Reduces number and weight of attacks of stenocardia and increases portability of an exercise stress. Due to increase in end diastolic pressure in a left ventricle and increases in stretching of muscle fibers of ventricles can increase oxygen requirement, especially at patients with the chronic heart failure (CHF).
The antiarrhytmic effect is caused by elimination of aritmogenny factors (tachycardia, a superactivity of a sympathetic nervous system, the increased content of cyclic adenosinemonophosphate, arterial hypotension), reduction of speed of spontaneous excitement of sinus and ectopic pacemakers and delay of artioventrikulyarny (AV) carrying out (it is preferential in antegrade and, to a lesser extent, in retrograde the directions through an AV node) and on additional ways.
At use in average therapeutic doses, unlike non-selective beta adrenoblockers, exerts less expressed impact on the bodies containing beta2-adrenoretseptror (a pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchial tubes and a uterus) and on carbohydrate metabolism, does not cause a delay of ions of sodium (Na+) in an organism; expressiveness of atherogenous action does not differ from effect of propranolol. At use in high doses (200 mg and more) the blocking effect renders on both subtypes of beta adrenoceptors, mainly, in bronchial tubes and unstriated muscles of vessels.

Pharmacokinetics. Absorption - 80 - 90%, meal does not influence absorption. The maximum concentration in a blood plasma is observed in 1 - 3 h, communication with proteins of a blood plasma about 30%.
Permeability through a blood-brain barrier and a placental barrier - low, secretion with breast milk - low.
The elimination half-life of 10-12 hours is metabolized in a liver with formation of inactive metabolites. About 98% are removed by kidneys, 50% are brought out of them in not changed look, less than 2% with bile.

Indications to use:

- arterial hypertension;
- coronary heart disease: prevention of attacks of stenocardia.

Route of administration and doses:

KOPOHAЛ® accept inside, in the morning on an empty stomach, without chewing, with a small amount of liquid.
At arterial hypertension and coronary heart disease (prevention of attacks of stable stenocardia) the initial dose makes 2,5 - 5 mg of 1 times a day. If necessary the dose is increased to 10 mg of 1 times a day. Maximum daily dose of-20 mg/days. Patients about a renal failure at clearance of creatinine have less than 20 ml/min. or with the expressed abnormal liver functions the maximum daily dose - 10 mg.
Dose adjustment is not required from elderly patients.

Precautionary measures at use
 Liver failure, renal failure (clearance of creatinine less than 20 ml/min.), a metabolic acidosis, a pheochromocytoma (at the accompanying use of alpha adrenoblockers), a diabetes mellitus in a decompensation stage, an atrioventricular block of the I degree, Printsmetal's stenocardia, a restrictive cardiomyopathy, inborn heart diseases or defects of valves of heart with the expressed hemodynamic disturbances, chronic heart failure with a myocardial infarction within the last 3 months, psoriasis, a depression (including in the anamnesis), heavy allergic reactions in the anamnesis, pregnancy, advanced age, a rigid diet, carrying out the desensibilizing immunotherapy allergens and extracts of allergens.

Features of use:

It is impossible to interrupt sharply treatment because of danger of development of a syndrome of "cancellation" (heavy arrhythmias and a myocardial infarction). Cancellation is carried out gradually, reducing a dose within 2 weeks and more (lower a dose by 25% in 3-4 days).

Side effects:

Frequency: very often (more or equally 1/10); often (more than 1/100, less than 1/10); infrequently (more than 1/1000, less than 1/100); seldom (more than 1/10000, less than 1/1000); very seldom (less than 1/10000, including separate messages).
From the central nervous system: infrequently - increased fatigue, an adynamy, dizziness, a headache, drowsiness or sleeplessness, a depression, it is rare - hallucinations, night "nightmares", spasms.
From sense bodys: seldom - a vision disorder, reduction of secretion of the lacrimal liquid, dryness and morbidity of eyes, a hearing disorder; very seldom - conjunctivitis.
From cardiovascular system: very often - a sinus bradycardia, it is frequent - a lowering of arterial pressure, manifestation of a vasomotor spasm (strengthening of disturbance of peripheric circulation, a cold snap of the lower extremities, paresthesias), infrequently - disturbance of artioventrikulyarny conductivity, orthostatic hypotension, a decompensation of chronic heart failure, peripheral hypostases.
From the alimentary system: often - dryness of a mucous membrane of an oral cavity, nausea, vomiting, diarrhea, a lock, it is rare - hepatitis.
From respiratory system: infrequently - difficulty of breath at appointment in high doses (selectivity loss) and/or at predisposed patients - laringo-and a bronchospasm; seldom - a nose congestion, allergic rhinitis.
From endocrine system: seldom - a hyperglycemia (patients with a diabetes mellitus have 2 types), a hypoglycemia (at the patients receiving insulin.
Allergic reactions: seldom - a skin itch, rash, a small tortoiseshell.
From integuments: seldom - sweating strengthening, a dermahemia, is very rare - psoriazopodobny skin reactions, an aggravation of symptoms of psoriasis, an alopecia.
From a musculoskeletal system: infrequently - muscular weakness, spasms in gastrocnemius muscles, an arthralgia.
Laboratory indicators: seldom - increase in activity of "hepatic" transaminases, a gipertriglitseridemiya, in some cases - thrombocytopenia, an agranulocytosis.
Influence on a fruit: pre-natal growth inhibition, hypoglycemia, bradycardia.
Others: very seldom - disturbance of a potentiality, is rare - a syndrome of "cancellation" (strengthening of attacks of stenocardia, increase in arterial pressure).

Interaction with other medicines:

The allergens used for an immunotherapy or extracts of allergens for skin tests increase risk of emergence of heavy system allergic reactions or an anaphylaxis at the patients receiving бисопролол.
Yodosoderzhashchy X-ray contrast medicines for intravenous administration increase risk of development of anaphylactic reactions.
Phenytoinum at intravenous administration, medicines for inhalation anesthesia (derivatives of hydrocarbons) increase expressiveness of cardiodepressive action and probability of a lowering of arterial pressure.
Changes efficiency of insulin and hypoglycemic means for intake, masks symptoms of the developing hypoglycemia (tachycardia, increase in arterial pressure). Reduces clearance of lidocaine and xanthines (except Diphyllinum) and increases their concentration in plasma, especially at patients with initially increased clearance of theophylline under the influence of smoking.
Anti-hypertensive action non-steroidal anti-inflammatory drugs (a delay of ions of sodium (Na+) and blockade of synthesis of prostaglandin kidneys) weaken, glucocorticosteroids and estrogen (a delay of ions of sodium).
Cardiac glycosides, Methyldopum, Reserpinum and гуанфацин, blockers of "slow" calcium channels (verapamil, diltiazem), Amiodaronum and other antiarrhytmic means increase risk of development or aggravation of bradycardia, AV of blockade, a cardiac standstill and heart failure.
Nifedipine can lead to a considerable lowering of arterial pressure.
Diuretics, clonidine, sympatholytics, гидралазин and other hypotensive medicines can lead to an excessive lowering of arterial pressure.
Extends action of not depolarizing muscle relaxants and increases anticoagulating effect of coumarins.
Rub - and tetracyclic antidepressaita, antipsychotic means (neuroleptics, including сультоприд), ethanol, sedative and somnolent medicines strengthen oppression of the central nervous system, can provoke disturbances of a cordial rhythm, bradycardia and orthostatic hypotension.
Simultaneous use with monoamine oxidase inhibitors, owing to considerable strengthening of anti-hypertensive action is not recommended, having rummaged in treatment between reception of monoamine oxidase inhibitors and a bisoprolola has to make not less than 14 days.
Not hydrogenated alkaloids of an ergot increase risk of development of disturbances of peripheric circulation.
Ergotamine increases risk of development of disturbance of peripheric circulation; Sulfasalazinum increases concentration of a bisoprolol in plasma; rifampicin shortens a drug elimination half-life.
There is a potential danger of the additive effect with development of hypotension and/or considerable bradycardia, when sharing with beta adrenoblockers for topical administration (eye drops).
Decrease in anti-hypertensive effect of drug against the background of use of adrenaline and noradrenaline is noted.
The probability of disturbances of automatism, conductivity and contractility of heart increases (mutually) against the background of therapy by hinidinovy drugs (мефлохин, chloroquine).
In case of shock or the arterial hypotension caused floktafeniny at combined use decrease in compensatory cardiovascular reactions is possible.
At simultaneous use with Baclofenum or amifostiny strengthening of anti-hypertensive action is also noted.

Features of use by pregnant women, women during breastfeeding, the children, adults having chronic diseases
 At pregnancy of KORONAL appoint only according to strict indications if the estimated advantage for mother exceeds potential risk for a fruit. In 72 hours before childbirth administration of drug of KORONAL needs to be stopped in connection with possible development in the fruit/newborn of bradycardia, arterial hypotension, a hypoglycemia and respiratory depression.
If administration of drug of KORONAL is necessary in the period of a lactation, breastfeeding needs to be stopped.
Use of drug KORONAL for children up to 18 years is contraindicated as efficiency and safety are not established.
Control of the patients accepting KORONAL has to include measurement of heart rate and arterial pressure (in an initiation of treatment - daily, then 1 time in 3-4 months), carrying out the electrocardiogram, definition of concentration of glucose in blood at patients with a diabetes mellitus (1 time in 4-5 months). At elderly patients it is recommended to monitor function of kidneys (1 times in 4-5 months).
It is necessary to train the patient in a technique of calculation of heart rate and to instruct about need of medical consultation at heart rate less than 50 beats/min.
Before an initiation of treatment it is recommended to conduct a research of function of external respiration at patients with the burdened bronchopulmonary anamnesis.
Approximately at 20% of patients with stenocardia beta adrenoblockers are inefficient. The main reasons - heavy coronary atherosclerosis with a low threshold of ischemia (heart rate less than 100 beats/min) and the increased final diastolic volume of a left ventricle breaking a subendocardial blood stream.
At "smokers" efficiency of beta adrenoblockers is lower.
The patients using contact lenses have to consider that against the background of treatment reduction of products of the lacrimal liquid is possible.
At use for patients from feokhrotsitomy there is a risk of development of paradoxical arterial hypertension (if it is previously not reached effective alpha адреноблокада).
At a thyrotoxicosis бисопролол can disguise certain clinical signs of a treotoksikoz (for example, tachycardia). Sharp cancellation at patients with a thyrotoxicosis is contraindicated as it is capable to strengthen symptomatology.
At a diabetes mellitus can mask the tachycardia caused by a hypoglycemia. Unlike non-selective beta adrenoblockers practically does not strengthen the hypoglycemia caused by insulin and recovery of concentration of glucose in blood to normal level does not detain.
At a concomitant use of a clonidine its reception can be stopped only in several days after drug withdrawal of KORONAL.
Strengthening of expressiveness of hypersensitivity reaction and lack of effect of usual doses of Epinephrinum against the background of the burdened allergological anamnesis is possible. In case of need performing planned surgical treatment carry out drug withdrawal for 48 h prior to the beginning of the general anesthesia. If the patient accepted drug before operation, it should pick up medicine for the general anesthesia with the minimum negative inotropic effect.
Reciprocal activation of a vagus nerve can be eliminated with intravenous administration of atropine (1-2 mg).
The medicines reducing stocks of catecholamines (including, Reserpinum), can strengthen effect of beta adrenoblockers therefore the patients accepting such combinations of medicines have to be under constant observation of the doctor regarding identification of the expressed lowering of arterial pressure or bradycardia.
Patients with bronkhospastichesky diseases can appoint cardioselective beta adrenoblockers in case of intolerance and/or inefficiency of other hypotensive medicines. The overdose is dangerous by development of a bronchospasm. In case of emergence in patients of advanced age of the accruing bradycardia (less than 50 beats/min), the expressed lowering of arterial pressure (systolic arterial pressure below 100 mm hg), AV of blockade, it is necessary to reduce a dose or to stop treatment.
It is recommended to stop therapy at development of a depression.
Drug should be cancelled before a research of content in blood and urine of catecholamines, a normetanefrin and vanilinmindalny acid; credits of antinuclear antibodies.

Influence on ability to manage vehicles and mechanisms
 During treatment it is necessary to be careful during the driving and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Contraindications:

Hypersensitivity to components of drug and other beta adrenoblockers, shock (including cardiogenic), an acute heart failure, chronic heart failure in a stage of a decompensation, AV blockade of the II-III degree (without artificial pacemaker), sinuatrial blockade, a sick sinus syndrome, the expressed bradycardia, a cardiomegaly (without symptoms of heart failure), arterial hypotension (systolic arterial pressure less than 100 mm hg, especially at a myocardial infarction); bronchial asthma and a chronic obstructive pulmonary disease in the anamnesis; a concomitant use of monoamine oxidase inhibitors (MAO) (except for MAO inhibitors of V type), the accompanying use of a floktafenin and sultoprid, late stages of disturbance of peripheric circulation, a Raynaud's disease, the lactation period, age up to 18 years (efficiency and safety are not established).

Overdose:

Symptoms: arrhythmia, ventricular premature ventricular contraction, the expressed bradycardia, AV blockade, the expressed lowering of arterial pressure, an acute heart failure, a Crocq's disease, breath difficulty, a bronchospasm, dizziness, unconscious states, spasms.
Treatment: a gastric lavage and purpose of the adsorbing medicines; symptomatic therapy: at the developed AV to blockade - intravenous (in/in) 1-2 mg of atropine, Epinephrinum or statement of a temporary pacemaker; at ventricular premature ventricular contraction - lidocaine (the drugs Ia of a class are not used); at a lowering of arterial pressure - the patient has to be in the provision of Trendelnburga; if there are no fluid lungs signs - intravenously plasma substituting solutions, at inefficiency - introduction of Epinephrinum, dopamine, Dobutaminum (for maintenance of chronotropic and ionotropny action and elimination of the expressed lowering of arterial pressure); at heart failure - cardiac glycosides, diuretics, a glucagon; at spasms - intravenously diazepam; at a bronchospasm - beta2-adrenostimulyator it is inhalation.

Storage conditions:

Period of validity 2 years. Drug cannot be used after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets film coated 5 mg, 10 mg.
On 10 tablets in the blister from PVC/PE/PVDC-AL or in the blister from A1/A1. On 1, 3, 6 or 10 blisters together with the application instruction place in a cardboard pack.