Bisoprolol of 5 mg

General characteristics. Structure:

Active ingredient: the bisoprolola fumarates – 0,005 g or 0,01 g,
excipients: lactoses monohydrate (sugar milk) – 0,0973 g or 0,0923 g, calcium a carbonate – 0,0145 g, cellulose microcrystallic – 0,0145 g, croscarmellose sodium (primelloza) – 0,0029 g, talc – 0,00435 g, magnesium stearate – 0,00145 g;
structure of a cover: for a dosage of 5 mg – Opadray the II White (polyvinyl alcohol – 40%, titanium dioxide – 25%, talc – 20,2%, a macrogoal (polyethyleneglycol) – 14,8%) – 0,004841 g, a silicone emulsion – 0,000159 g;
for a dosage of 10 mg – Opadray the II White (polyvinyl alcohol – 40%, titanium dioxide – 25%, talc – 20,2%, a macrogoal (polyethyleneglycol) – 14,8%) – 0,004737 g, dye ferrous oxide of red E 172 - 0,000052 g, a macrogoal (polyethyleneglycol) – 0,000052 g, a silicone emulsion – 0,000159 g.

Pharmacological properties:

Pharmacodynamics. The selection beta1-adrenoblocker without own sympathomimetic activity; has anti-hypertensive, antiarrhytmic and anti-anginal effect. Blocking heart beta1-adrenoceptors in low doses, reduces stimulated catecholamines formation of cyclic adenosinemonophosphate (tsAMF) from adenosinetriphosphate (ATP), reduces intracellular current of calcium ions (Sa2+), 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 at the beginning of use of beta adrenoblockers, in the first 24 h, 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.
The anti-hypertensive effect is connected with reduction of minute volume of blood, sympathetic stimulation of peripheral vessels, decrease of the activity system renin-angiotensin-aldosteronovoy (has bigger value for patients with initial hypersecretion of a renin), 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 influence on the central nervous system. 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 and decrease in contractility, lengthening of a diastole, improvement of perfusion of a myocardium. Due to increase in end diastolic pressure in a left ventricle and increases in stretching of muscle fibers of ventricles can increase the need of a myocardium for oxygen, especially at patients with the chronic heart failure (CHF).
Unlike non-selective beta adrenoblockers at appointment in average therapeutic doses exerts less expressed impact on the bodies containing beta2-adrenoceptors (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. At use in high doses renders the blocking effect on both subtypes of beta adrenoceptors.

Pharmacokinetics. Bisoprolol is almost completely soaked up from digestive tract (80-90%). Meal does not influence drug absorption. The maximum concentration in a blood plasma is reached in 2-3 hours. Communication with proteins of a blood plasma about 35%. Permeability through a blood-brain barrier and a placental barrier low, secretion with breast milk low.
It is metabolized in a liver. The elimination half-life (T1/2) of 9-12 hours, is extended at a renal failure (at clearance of creatinine less
40 ml/min. – by 3 times), at advanced age, at liver diseases (at cirrhosis increases to 21,7 h). It is removed by kidneys – 50% in not changed look, less than 2% through intestines.

Indications to use:

Arterial hypertension.
Coronary heart disease: prevention of attacks of stable stenocardia.

Route of administration and doses:

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) it is recommended to accept 5 mg once. If necessary the dose is increased to 10 mg of 1 times a day. The maximum daily dose – 20 mg. At patients with a renal failure (clearance of creatinine less than 20 ml/min.) or with the expressed abnormal liver functions the maximum daily dose of-10 mg. Dose adjustment is not required from elderly patients.

Features of use:

Control of the patients accepting Bisoprolol has to include observation of ChSS and the ABP (in an initiation of treatment - daily, then 1 time in 3-4 months), the electrocardiogram (ECG), concentration of glucose of blood at patients 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 patients in a technique of calculation of ChSS and to instruct about need of medical consultation at ChSS 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 stenocardia beta adrenoblockers are inefficient. The main reasons - heavy coronary atherosclerosis with a low threshold of ischemia (ChSS less than 100 beats/min) and the increase in 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 with a pheochromocytoma there is a risk of development of paradoxical arterial hypertension (if it is previously not reached effective alpha адреноблокада).
At a thyrotoxicosis Bisoprolol can mask certain clinical signs of a thyrotoxicosis (for example, tachycardia). Sharp cancellation at patients with a thyrotoxicosis is contraindicated as it is capable to strengthen symptomatology.
At a diabetes mellitus can disguise 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 value does not detain.
At a concomitant use of a clonidine its reception can be stopped only in several days after Bisoprolol's cancellation.
Strengthening of expressiveness of reaction of hypersensitivity and lack of effect of usual doses of Epinephrinum (adrenaline) 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 (for example, 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 detection of arterial hypotension or bradycardia.
Patients with bronkhospastichesky diseases can appoint cardioselective adrenoblockers in case of intolerance and/or inefficiency of other hypotensive medicines, but at the same time it is necessary to watch a dosage strictly. 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), arterial hypotension (systolic the ABP is lower
100 mm hg), AV of blockade, a bronchospasm, ventricular arrhythmias, heavy abnormal liver functions and kidneys needs to reduce a dose or to stop treatment. It is recommended to stop therapy at development of the depression caused by reception of beta adrenoblockers.
It is impossible to interrupt sharply treatment because of danger of development of heavy arrhythmias and a myocardial infarction. Cancellation is carried out gradually, reducing a dose during 2 weeks and more (lower a dose by 25% in 3-4 days).
It is necessary to cancel before a research of content in blood and urine of catecholamines, a normetanefrin and vanililmindalny acid, credits of antinuclear antibodies.
Influence on ability to driving of motor transport and to control of mechanisms
During treatment it is necessary to be careful at control of vehicles and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Frequency: very often (more or equally 1/10), it is frequent (more than 1/100, less than 1/10), infrequently (more than 1/1000, less than 1/100), is rare (more than 1/10000, less than 1/1000), is very rare (less than 1/10000, including separate messages).
From the central nervous system: very often - a headache (10,9%), it is frequent - dizziness (3,5%), sleeplessness (2,5%), an adynamy (1,5%), a depression (0,2%), drowsiness, increased fatigue, is rare - a loss of consciousness, hallucinations, "dreadful" dreams, spasms, confusion of consciousness or short-term loss of memory.
From sense bodys: seldom - the vision disorder, reduction of secretion of the lacrimal liquid, dryness and morbidity of eyes, a hearing disorder, is very rare - conjunctivitis.
From cardiovascular system: infrequently - a sinus bradycardia (0,5%), it is rare - the expressed decrease in the ABP, is very rare - disturbance
AV of conductivity, orthostatic hypotension, HSN decompensation, peripheral hypostases, manifestation of a vasomotor spasm (strengthening of disturbance of peripheric circulation, cold snap of the lower extremities, Reynaud's syndrome, paresthesias), stethalgia.
From the alimentary system: often - diarrhea (3,5%), nausea (2,2%), vomiting (1,5%), dryness of a mucous membrane of an oral cavity (1,3%), a lock, it is rare - hepatitis.
From respiratory system: often - a nose congestion (4%), difficulty of breath at appointment in high doses (selectivity loss), at predisposed patients - laringo-and a bronchospasm (2,2%).
From endocrine system: hyperglycemia (diabetes mellitus of the II type), hypoglycemia (diabetes mellitus of the I type).
Allergic reactions: seldom - a skin itch, rash, a small tortoiseshell, allergic rhinitis.
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.
Others: disturbance of a potentiality, syndrome of "cancellation" (strengthening of attacks of stenocardia, increase in the ABP).

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 Bisoprolol.
Phenytoinum at intravenous administration, medicines for inhalation general anesthesia (derivatives of hydrocarbons) increase expressiveness of cardiodepressive action and probability of decrease in the ABP.
Iodinated X-ray contrast diagnostic intravenous agents increase risk of development of anaphylactic reactions.
Bisoprolol changes efficiency of insulin and hypoglycemic means for intake, masks symptoms of the developing hypoglycemia (tachycardia, increase in the ABP).
Anti-hypertensive effect non-steroidal anti-inflammatory drugs (a delay of ions of sodium and blockade of synthesis of prostaglandin kidneys) weaken, glucocorticosteroids and estrogen (a delay of ions of sodium).
Cardiac glycosides, Methyldopum, Reserpinum and гуанфацин increase risk of development or aggravation of bradycardia, an atrioventricular block, cardiac standstill and heart failure.
Bisoprolol's combinations with antagonists of calcium (verapamil, diltiazem, bepridit) are not recommended, at their intravenous administration, in connection with growth of negative influence on inotropic function of a myocardium, AV-conductivity and the ABP.
Can lead combined use of nifedipine and Bisoprolol to considerable decrease in the ABP.
At simultaneous use of Bisoprolol and antiarrhytmic means of a class I (Disopyramidum, quinidine, hydroquinidine) deterioration in atrioventricular conductivity and negative inotropic action is possible (clinical observation and control of an electrocardiography is necessary).
At simultaneous use of Bisoprolol and antiarrhytmic means of a class III (for example, Amiodaronum) deterioration in intra-atrial conduction is possible.
At simultaneous use of drug Bisoprolol and other beta adrenoblockers, including contained in eye drops, is possible an action synergism.
Bisoprolol with beta-adrenergic agonists (for example, изопреналин, Dobutaminum) can lead simultaneous use of drug to decrease in effect of both drugs.
Bisoprolol's combination with beta and alpha адреномиметиками (for example, Norepinephrinum, Epinephrinum), can strengthen vasopressor effects of these means arising with participation of alpha adrenoceptors, leading to increase in the ABP.
Diuretics, clonidine, sympatholytics, гидралазин and other anti-hypertensive drugs can lead to excessive decrease in the ABP.
At simultaneous use of Bisoprolol and a meflokhin the risk of bradycardia increases.
The concomitant use of Bisoprolol with floktafeniny and sultopridy is contraindicated.
Action of not depolarizing muscle relaxants and anticoagulating effect of coumarins during treatment by Bisoprolol can be extended.
Rub - and tetracyclic antidepressants, antipsychotic means (neuroleptics), ethanol, sedative and somnolent medicines strengthen oppression of the central nervous system. Simultaneous use of Bisoprolol with MAO inhibitors (except MAO-B) owing to considerable strengthening of hypotensive action is not recommended. Having rummaged in treatment between reception of MAO inhibitors and Bisoprolol has to make not less than 14 days.
Reduces clearance of lidocaine and xanthines (except a diprofillin) and increases their concentration in a blood plasma, especially at patients with initially increased clearance of theophylline under the influence of smoking.
Sulfasalazinum increases Bisoprolol's concentration in a blood plasma.
Rifampicin shortens Bisoprolol elimination half-life.

Contraindications:

Acute heart failure or chronic heart failure in a decompensation stage (demanding performing inotropic therapy); cardiogenic shock; an atrioventricular block of II and III degrees, without electrocardiostimulator; sinuatrial blockade; sick sinus syndrome; bradycardia (heart rate (HR) less than 60 beats/min); a cardiomegaly (without symptoms of heart failure); arterial hypotension (systolic pressure is less than 100 mm of mercury); severe forms of bronchial asthma and obstructive pulmonary disease; heavy disturbances of peripheric circulation, Reynaud's syndrome; lactation period; a concomitant use of inhibitors of a monoaminooxidase (MAO) except for MAO-B; hypersensitivity to Bisoprolol, components of drug and to other beta adrenoblockers; hereditary lactose intolerance, deficit of lactase, syndrome of glyukozo-galaktozny malabsorption; a pheochromocytoma (without simultaneous use of alpha adrenoblockers); metabolic acidosis; concomitant use of a floktafenin, sultoprid; simultaneous intravenous administration of verapamil, diltiazem; age up to 18 years (efficiency and safety are not established).

Overdose:

Symptoms: a hypoglycemia, arrhythmia, ventricular premature ventricular contraction, the expressed bradycardia, an atrioventricular block, the expressed lowering of arterial pressure, an acute heart failure, cyanosis of nails of fingers or palms, breath difficulty, a bronchospasm, dizziness, a syncope, spasms.
Treatment: gastric lavage, purpose of enterosorbents (absorbent carbon) and symptomatic therapy:
- at the developed atrioventricular block intravenously enter 1-2 mg of atropine, Epinephrinum or temporarily put a pacemaker;
- at ventricular premature ventricular contraction enter lidocaine (the drugs IA of a class are not used);
- at the expressed decrease in the ABP the patient has to be in the provision of Trendelenburga if there are no fluid lungs signs - plasma substituting solutions intravenously, at inefficiency enter Epinephrinum (adrenaline), a dopamine, Dobutaminum (for maintenance of chronotropic and inotropic action and elimination of the expressed decrease in the ABP);
- at heart failure apply cardiac glycosides, diuretics;
- at spasms - intravenously diazepam, at a bronchospasm - it is inhalation beta2 - sympathomimetics;
- at a hypoglycemia – intravenous administration of solution of a dextrose (glucose);
- at bradycardia – atropine, statement of a pacemaker.

Storage conditions:

In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 5 mg and 10 mg.
On 10 tablets in a blister strip packaging.
On 1, 2, 3, 4 or 5 blister strip packagings together with the application instruction in a pack cardboard.