Bisoprolol

General characteristics. Structure:

Active ingredient: bisoprolol;

1 tablet contains a bisoprolol of a fumarat in terms of 100% substance of 2,5 mg, 5 mg, 10 mg;

excipients (tablets on 2,5 mg): cellulose microcrystallic (102), calcium hydrophosphate anhydrous, кросповидон, silicon dioxide colloid anhydrous, magnesium stearate;

excipients (tablets on 5 mg and 10 mg): lactoses monohydrate, cellulose microcrystallic (102), calcium hydrophosphate anhydrous, кросповидон, silicon dioxide colloid anhydrous, yellow decline of FCF (E 110) LAKE, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. The selection β1-адреноблокатор. At use in therapeutic doses has no internal sympathomimetic activity and clinically expressed membrane stabilizing properties. Has anti-anginal effect: reduces the need of a myocardium for oxygen thanks to reduction of ChSS and cordial emission and a lowering of arterial pressure, increases supply of a myocardium with oxygen due to reduction of diastolic pressure and lengthening of a diastole.

Has hypotensive effect thanks to reduction of cordial emission, braking of secretion of a renin by kidneys, and also impact on baroreceptors of an aortic arch and a carotid sine. At prolonged use of Bisoprolol the increased peripheric vascular resistance decreases, first of all. At chronic heart failure means oppresses the system activated sympathoadrenal and renin-angiotensin-aldosteronovuyu. Bisoprolol has very low affinity with β2-рецепторами smooth muscles of bronchial tubes and vessels, and also with β2-рецепторами endocrine system. Drug only in isolated cases can influence smooth muscles of bronchial tubes and peripheral arteries, and also glucose metabolism. At single use action of a bisoprolol remains within 24 hours.

Pharmacokinetics. After intake Bisoprolol is well adsorbed from digestive tract. Bioavailability makes about 90% and does not depend on meal. The maximum concentration in a blood plasma is reached in 1-3 hours after reception. Linkng with proteins of a blood plasma makes about 30%.

The effect of "the first passing" through a liver is expressed slightly (less than 10%). In a liver about 50% of a dose with formation of inactive metabolites biotransformirutsya. About 98% are brought out of an organism by kidneys, 50% – in not changed look, the rest – in the form of metabolites, about 2% of a dose – through intestines. Time of semi-removal makes 10-12 hours.

Pharmaceutical characteristics.

Main physical and chemical properties: tablets on 2,5 mg of white color, a round form with a biconvex surface, with risky or without risks. On a surface of tablets the mramornost is allowed;

tablets on 5 mg of a round form with a biconvex surface, light pink color, with risky or without risks. On a surface of tablets impregnations are allowed;

tablets on 10 mg of a round form with a flat surface, with a facet and risky, light pink color. On a surface of tablets impregnations are allowed.

Indications to use:

Arterial hypertension;
coronary heart disease (stenocardia);
chronic heart failure.

Route of administration and doses:

Drug should be accepted in the morning, without chewing, it is not dependent on meal, washing down with a small amount of liquid.

Treatment of arterial hypertension and stable stenocardia.

At arterial hypertension and stable stenocardia the initial dose makes 2,5-5 mg a day, an average daily dose – 5-10 mg, the maximum daily dose – 20 mg.

Treatment of chronic heart failure.

At chronic heart failure drug is appointed to patients with moderately expressed and heavy heart failure with reduced systolic function (fraction of emission ≤ 35% according to an echocardiography) by whom are in a condition of stabilization without aggravation for the last six weeks. The initial dose makes 1,25 mg once in days within the first week (use drugs of a bisoprolol with a possibility of such dosing). For the 2nd week of reception 2,5 mg a day are appointed. Within the 3rd week the medical dose makes 3,75 mg a day (use drugs of a bisoprolol with a possibility of such dosing). From the 4th to the 8th week of reception 5 mg are appointed. Then the dose is increased to 7,5 mg (from the 8th to the 12th week). After the 12th week of treatment the maximum daily dose – 10 mg is appointed. Increase in a dose of drug is regulated by indicators of heart rate, arterial pressure, the general condition of the patient.

The maximum dose – 10 mg a day.

Bisoprolol at treatment of patients with chronic heart failure can be combined with angiotensin-converting enzyme inhibitor, diuretic and cardiac glycoside. After an initiation of treatment the patient with chronic heart failure has to be inspected by drug in a dose of 1,25 mg within 4 hours (arterial pressure, ChSS, conductivity disturbance, strengthening of symptoms of heart failure); if necessary drug is cancelled.

Patients with a liver and renal failure.

For patients with an abnormal liver function or kidneys easy or moderate severity selection of a dose usually does not need to be carried out.

For patients with the expressed depression of function of kidneys (the clearance of creatinine is less than 20 ml/min.) and the patient with a severe form of an abnormal liver function the dose should not exceed 10 mg of drug.

The dose is selected individually.

The course of treatment long also depends on character and the course of a disease.

To graduate slowly with a gradual dose decline.

It is impossible to stop treatment sharply!

Features of use:

Use during pregnancy and feeding by a breast.

It is not recommended to use drug during pregnancy and feeding by a breast.
Children.

Drug is not used for treatment of children due to the lack of data on safety and efficiency of drug.

It is impossible to stop treatment sharply, it is necessary to graduate slowly, with a gradual dose decline.

Drug should be used with care at:

diabetes mellitus with sharp fluctuation of level of glucose in blood, considering that symptoms of a hypoglycemia can be hidden (for example, tachycardia, a heart consciousness, the increased sweating);

to rigid diet;

the desensibilizing therapy;

to atrioventricular block І degrees;

Printsmetal's stenocardias;

disturbances of peripheric circulation (increase in complaints, especially in an initiation of treatment is possible).
Before an initiation of treatment it is recommended to conduct a research of functions of external respiration by the patient with bronchial asthma in the anamnesis.

If an operative measure using the general anesthesia is planned it is necessary to warn the anesthesiologist about reception of blockers of β-adrenoceptors surely.......... It is not recommended to apply blockers of β-adrenoceptors during surgical interventions, it can increase risk of developing of arrhythmias and ischemia of a myocardium.

Dose it is necessary to reduce and stop gradually administration of drug in 48 hours prior to the general anesthesia.

Not to use drug the patient with a pheochromocytoma if the effective α-adrenoblokada is previously not reached.

Symptoms of a thyrotoxicosis can be disguised against the background of administration of drug.

During treatment by drug it is impossible to take alcohol.

Drug contains lactose therefore patients with rare hereditary forms of intolerance of a galactose, insufficiency of lactase or a syndrome of glyukozo-galaktozny malabsorption should not use drug.

Ability to influence speed of response at control of motor transport or work with other mechanisms. In individual cases in an initiation of treatment and when replacing drug ability to drive the car or difficult mechanisms can be reduced.

Side effects:

Undesirable effects on the frequency of emergence classify by such categories:

very often (> 1/10), it is frequent (> 1/100 and <1/10), sometimes (> 1/1000 and <1/100), is rare (> 1/10000 and <1/1000), is very rare (<1/10000).

From a nervous system: often – dizziness, a headache (especially in an initiation of treatment, are usually poorly expressed and pass within 1-2 weeks); sometimes – a sleep disorder, a depression; seldom – hallucinations, paresthesias.

From an organ of sight: seldom – a vision disorder, decrease in lacrimation (it is necessary to consider when carrying contact lenses); very seldom – conjunctivitis.

From an acoustic organ: seldom – a hearing disorder.

From cardiovascular system: very often – bradycardia (at patients with chronic heart failure); often – a cryesthesia or numbness of extremities, signs of deterioration in a course of heart failure in an initiation of treatment (at patients with chronic heart failure); sometimes – disturbance of atrioventricular conductivity (at patients with arterial hypertension and coronary heart disease), orthostatic hypotension.

From respiratory system: sometimes – a bronchospasm at patients with bronchial asthma in the anamnesis and chronic obstructive respiratory diseases; seldom – allergic rhinitis.

From digestive tract: often – nausea, vomiting, a diyard, a lock.

From gepatobiliarny system: increase in activity of liver enzymes in a blood plasma (nuclear heating plant, ALT), hepatitis.

From skin and a musculoskeletal system: sometimes – muscular weakness, spasms; seldom – hypersensitivity reactions (an itch, the increased perspiration, rash); very seldom – the hair loss, at treatment by blockers of β-receptors can be observed an aggravation of symptoms of patients with psoriasis in the form of psoriasis rash.

From endocrine system: seldom – metabolism disturbances (increases in level of triglycerides in blood).

From urinogenital system: seldom – disturbance of a potentiality.

General frustration: often – an adynamy (at patients with chronic heart failure), increased fatigue (especially in an initiation of treatment, are usually poorly expressed and pass within 1-2 weeks); sometimes – an adynamy (at patients with arterial hypertension and coronary heart disease).

Interaction with other medicines:

Blockers of calcium channels (dihydropyridine derivatives) are potentsiirut by hypotensive effect of Bisoprolol. At simultaneous use with blockers of β-receptors symptoms of a hypoglycemia can be hidden. Simultaneous use with verapamil, diltiazem, a clonidine, metildopy, moksinidiny, Reserpinum can lead to development or deterioration in bradycardia, an atrioventricular block, heart failure, a lowering of arterial pressure.

At use of Bisoprolol with antiarrhytmic means (Phenytoinum, Disopyramidum, lidocaine, флекаинид, Amiodaronum) there can be a disturbance of conductivity and a negative inotropic effect.

At simultaneous use with parasympathomimetic drugs time of atrioventricular conductivity can increase and the risk of developing of bradycardia increases.

At simultaneous use of Bisoprolol and β-blockers ((((((((((that which contain in eye drops for treatment of glaucoma) action of a bisoprolol can amplify.

At simultaneous use with insulin and anti-diabetic drugs for oral administration the risk of development of a hypoglycemia increases.

At simultaneous use with means for anesthesia the risk of developing of arrhythmias and ischemia of a myocardium can increase.

Use with cardiac glycosides (foxglove drugs) can lead to decrease in heart rate, disturbance of atrioventricular conductivity.

The hypotensive effect of a bisoprolol weakens at simultaneous use with non-steroidal anti-inflammatory drugs.

At simultaneous use with β-sympathomimetics ((((((((((Dobutaminum, орципреналин) the effect of both means decreases.

Sympathomimetics which activate α-and β-adrenoceptors ((((((((((adrenaline, noradrenaline) increase arterial pressure and strengthen the phenomena of the alternating lameness.

Tricyclic antidepressants, barbiturates, фенотиазин strengthen hypotensive effect.

At simultaneous use with MAO inhibitors (except MAO inhibitors of V type) the hypotensive effect of drug increases (see the section "Contraindications").

Contraindications:

Heart failure in a decompensation stage;
cardiogenic shock;
atrioventricular block of II and III degrees;
sick sinus syndrome;
the expressed sinuatrial blockade;
symptomatic bradycardia (heart rate less than 50 beats per minute);
symptomatic arterial hypotension (systolic arterial pressure is lower
90 mm of mercury.);

heavy course of bronchial asthma and other obstructive respiratory diseases;
late stages of disturbance of peripheric circulation, Raynaud's disease;
not treated pheochromocytoma;
metabolic acidosis;
concomitant use of MAO inhibitors (except for MAO inhibitors of V type);
psoriasis (including in the family anamnesis);
pregnancy, feeding period breast;
children's age;
hypersensitivity to drug components.

Overdose:

Symptoms: bradycardia, arterial hypotension, heart failure, bronchospasm, hypoglycemia.

Treatment: to cancel drug, to wash out a stomach and to accept absorbent carbon. If necessary – a symptomatic treatment.

At bradycardia: intravenous administration of atropine.

At arterial hypotension: reception of vasoconstrictive drugs, intravenous administration of a glucagon.

At an atrioventricular block of II and III degrees: infusional introduction of an ortsiprenalin; if necessary – cardiostimulation.

Aggravation of symptoms at heart failure: intravenous administration of diuretic means.

At a bronchospasm: broncholitic drugs (for example, орципреналин), β2-адреномиметики and/or эуффилин.

At a hypoglycemia: intravenous administration of glucose.

Storage conditions:

Period of validity. 2 years (tablets on 2,5 mg). 3 years (tablets on 5 mg and 10 mg). Not to use drug after the termination of the period of validity specified on packaging. To store in protected from light and the place, unavailable to children, at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

Tablets on 2,5 mg. On 10 tablets in the blister. On 2 blisters enclosed in a pack.

Tablets on 5 mg and 10 mg. On 10 tablets in the blister. On 2 or 5 blisters enclosed in a pack.