Bisoprolol-Teva of the tab. of 5 mg No. 30

Pharmacological properties

Pharmacodynamics. bisoprolol — an active high-selection blocker β1-адренорецепторов, without internal sympathomimetic activity. has hypotensive and anti-anginal effect. the mechanism of antihypertensive action consists in decrease in minute volume of heart, reduction of sympathetic stimulation of peripheral vessels and oppression of release of renin kidneys. anti-anginal action is connected with blockade β1-адренорецепторов. bisoprolol reduces the need of a myocardium for oxygen due to reduction chss and warm emission and decrease hell, increases supply of a myocardium with oxygen due to reduction of end diastolic pressure and lengthening of a diastole. bisoprolol has very low affinity to β2-рецепторам unstriated muscles of bronchial tubes and vessels and also to β2-рецепторам an endocrine system.

Maximum effect of a bisoprolol occurs in 3–4 h after reception. T _½ makes 10–12 h of blood plasma that results in 24-hour efficiency after single dose of drug. The maximum antihypertensive effect is reached in 2 weeks of reception.

Pharmacokinetics. After oral administration, medicament is well absorbed in a GIT. The effect of the first passing through a liver is significant slightly that promotes high bioavailability — about 90%. Linking with proteins of blood plasma makes about 30%. The volume of distribution is 3.5 l/kg. The general clearance of a bisoprolol — 15 l/h

out of an organism in two ways. About 50% are metabolized in a liver with formation of inactive metabolites which are allocated with kidneys. Other 50% are allocated with kidneys in not changed look. Because of approximately identical participation of kidneys and a liver in removal of this medicament by the patient with a renal or liver failure of dose adjustment it is not required. The kinetics of a bisoprolol linear also does not depend on age.

Indication

Ag; ischemic heart disease (stenocardia); chronic heart failure with systolic dysfunction of a left ventricle (in a combination with inhibitors apf, diuretics, in case of need — cardiac glycosides).

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Tablet for oral administration.

AG, ischemic heart disease (stenocardia). The recommended dose makes 5 mg/days. In case of moderate AG (diastolic pressure is up to 105 mm Hg.) the dose of 2.5 mg approaches. If necessary the daily dose can be raised to 10 mg. Further increase in a dose is justified only in exceptional cases. The maximum recommended daily dose — 20 mg.

Change and dose adjustment is appointed by the doctor individually, depending on pulse rate and therapeutic advantage.

Bisoprolol is applied with care at patients with AG or ischemic heart disease which are followed by heart failure.

Chronic heart failure with systolic dysfunction of a left ventricle in a combination with APF inhibitors, diuretics, in case of need — cardiac glycosides. Standard therapy of chronic heart failure: APF inhibitors (or blockers of receptors of angiotensin in case of intolerance of APF inhibitors), blockers of β-adrenoceptors, diuretics and if necessary — cardiac glycosides.

Bisoprolol is appointed for treatment of patients with chronic heart failure without signs of aggravation. The doctor with experience of treatment of chronic heart failure has to carry out therapy.

Treatment of chronic heart failure bisoprololy should be begun with

according to the following scheme of titration and it is possible to adjust depending on individual reactions of an organism:

• 1.25 mg * a bisoprolol of the fumarat of 1 times a day during 1 week, raising to
• 2.5 mg * a bisoprolola of the fumarat of 1 times in day during the following 1 week, raising to
• 3.75 mg * a bisoprolola of the fumarat of 1 times in day during the following 1 week, raising to
• 5 mg of a bisoprolol of the fumarat of 1 times in day during the following 4 weeks, raising to
• 7.5 mg of a bisoprolol of the fumarat of 1 times in day during the following 4 weeks, raising to
• 10 mg of a bisoprolol of the fumarat of 1 times in day as maintenance therapy.

* to Apply

bisoprolol in the corresponding dosage. Bisoprolol in a dose of 2.5 mg is recommended to apply at the beginning of therapy of chronic heart failure.

Maximum recommended dose of a bisoprolol of the gemifumarat makes 10 mg of 1 times a day.

needs to carry out by

In an initiation of treatment of steady chronic heart failure regular monitoring. During a phase of titration the control of the following vital signs (the ABP, ChSS) and symptoms of progressing of heart failure is necessary.

treatment Correction. If during a phase of titration or after it deterioration in heart failure is observed, arterial hypotension or bradycardia develop, medicament dose adjustment is recommended that can demand a temporary dose decline of a bisoprolol or, perhaps, suspension of treatment. After stabilization of a condition of the patient the medicament treatment should be continued.

Course of treatment medicament long.

should not stop treatment suddenly and to change the recommended dose without consultation with the doctor as it can lead to aggravation of symptoms of the patient. In case of need treatment should be finished slowly, gradually reducing a dose.

Patients with a renal failure or a liver

AG, IBS. For patients with an abnormal liver function or kidneys easy and moderate severity usually patients do not need to carry out selection of a dose. With heavy disorders of renal function (clearance of creatinine of 20 ml/min.) and to patients with heavy abnormal liver functions it is not recommended to exceed a daily dose of 10 mg of a bisoprolol of the fumarat.

Chronic heart failure. Patients have no data of pharmacokinetics of a bisoprolol with chronic heart failure along with an abnormal liver function and/or kidneys therefore it is necessary to raise a dose with care. it is not required by

For patients of advanced age of dose adjustment of a bisoprolol to p. However administration of medicament is recommended to be begun with the minimum possible dose.

Children. Experience of use of medicament for children is absent therefore its use is not recommended.

Contraindication

Hypersensitivity to a bisoprolol or other components of drug; an acute heart failure or heart failure in a condition of a decompensation which demands inotropic therapy; cardiogenic shock; av-blockade of ii and iii of degree (except for that at patients with an artificial pacemaker); sick sinus syndrome; sinuatrial blockade; symptomatic bradycardia; symptomatic arterial hypotension; severe form oh or serious chronic obstructive illness of lungs; late stages of disturbance of peripheric circulation or Raynaud's disease; metabolic acidosis; not treated pheochromocytoma.

Side effects

from the immune system: emergence of antinuclear antibodies with such specific clinical symptoms as a volchanochnopodobny syndrome which disappeared after the treatment termination.

from mentality: sleep disorder, depression, nightmares, hallucinations.

metabolism Disturbance: increase in the TG level in blood, a hypoglycemia.

from nervous system: increased fatigue, exhaustion, dizziness *, headache *, loss of consciousness.

from an organ of sight: decrease in a slezootdeleniye (it is necessary to consider when carrying contact lenses), conjunctivitis.

from an organ of hearing: deterioration in hearing.

from heart: bradycardia, disturbance of AV conductivity, emergence/strengthening of symptoms of heart failure.

from vessels: cryesthesia or numbness of extremities, arterial hypotension (especially at patients with heart failure), deterioration in the course of the disease of Reynaud, strengthening of the available alternating lameness, orthostatic hypotension.

from a respiratory system: a bronchospasm at patients with BA or HOBL in the anamnesis, allergic rhinitis.

from digestive system: nausea, vomiting, diarrhea, abdominal pain, constipation.

from a liver: increase in level of liver enzymes (AlAT, AsAT) in blood plasma, hepatitis.

from skin and hypodermic fabric: reactions of hypersensitivity, including an itching, reddening, rash, inflows, the increased sweating, a hair loss, blockers of β-adrenoceptors can cause or aggravate psoriasis, psoriasis rashes.

from a musculoskeletal system: muscle weakness, spasms, arthropathy.

from a reproductive system: disturbance of potency.

General disorders: increased fatigue *, asthenia.

Laboratory researches: increase in the TG level, liver enzymes (AlAT, AsAT) *.

* Concerns only patients with AG or ischemic heart disease. These symptoms usually arise at the beginning of therapy, are mild and disappear during the first 1–2 weeks

in case of by-effects or undesirable reactions needs to inform the doctor immediately.

In an initiation of treatment with

regular monitoring of a condition of patients, especially it concerns elderly people.

should begin Treatment of stable chronic heart failure using a bisoprolol with

with a titration phase.

to Patients with an ischemic heart disease treatment should not be stopped suddenly needlessly as it can lead to tranzitorny aggravation of symptoms. Initiation and the terminations of treatment bisoprololy demands regular monitoring.

Now patients have

no sufficient therapeutic experience of treatment of heart failure with such diseases and morbid conditions: diabetes of the I type (insulin-dependent), heavy renal failures, heavy abnormal liver functions, a restrictive cardiomyopathy, congenital heart diseases, hemodynamically significant acquired valve heart diseases, a myocardial infarction within the last 3 months

needs to use with care medicament in a combination with Amiodaronum, considering risk of development of contractilny contractility and disturbance of warm conductivity (oppression of compensatory sympathetic reactions).

generally is not recommended to appoint

bisoprolol in a combination with antagonists of calcium of verapamilovy or diltiazemovy type and with antihypertensive medicaments of the central action.

should use Drug with care at patients at such states:

• bronchospasm (OH, obstructive respiratory diseases);
• diabetes with considerable fluctuations of level of glucose in blood because of a possibility of masking of symptoms of a hypoglycemia (tachycardia, heartbeat, the increased sweating);
• rigid diet;
• performing desensitization. As well as other blockers of β-adrenoceptors, bisoprolol the sensitivity to allergens can strengthen and increase weight of anaphylactic reactions. In such cases the treatment by epinephrine not always gives positive therapeutic effect;
• blockade of the I degree;
• Printsmetal's stenocardia;
• obliterating diseases of peripheral arteries (at the beginning of therapy strengthening of complaints is possible);
• general anesthesia.

needs to warn the anesthesiologist about reception of blockers of β-adrenoceptors surely. At patients to whom the general anesthesia is planned the use of blockers of β-adrenoceptors reduces cases of arrhythmia and ischemia of a myocardium during introduction to an anesthesia, intubations and the postoperative period. It is recommended to continue use of blockers of β-adrenoceptors during the perioperatsionny period. It is necessary to warn the anesthesiologist about reception of blockers of β-adrenoceptors as the doctor has to consider potential interaction with other medicines which can lead to bradyarrhythmia, reflex tachycardia and decrease in opportunities of the reflex mechanism of compensation of blood loss surely. In case of cancellation of a bisoprolol before surgeries a dose it is necessary to lower and stop gradually administration of medicament for 48 h to the general anesthesia.

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Combination of a bisoprolol with antagonists of calcium of group of verapamil or diltiazem, antiarrhytmic medicaments I of a class and antihypertensives of the central action are not recommended (see INTERACTIONS).

In spite of the fact that cardioselective blockers of β-adrenoceptors (β ₁ ) have less impact on function of lungs in comparison with non-selective blockers of β-adrenoceptors, it is necessary to avoid their use, as well as all blockers of β-adrenoceptors, in obstructive respiratory diseases if there are no good reasons for performing therapy. In case of need bisoprolol it is necessary to apply with care. Patients with obstructive respiratory diseases have a treatment bisoprololy it is necessary to begin with a low possible dose and it is necessary to watch a condition of patients in the relation emergence of new symptoms (such as asthma, intolerance of physical activities, cough).

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In OH or other chronic obstructive diseases of lungs which can cause symptoms showed the accompanying therapy by bronchodilators. In certain cases against the background of administration of medicament with OH because of increase in resistance of airways higher doses β ₂ - sympathomimetics can be required by patients.

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Sick psoriasis (including in the anamnesis) blockers of β-adrenoceptors (for example bisoprolol) to appoint advantage/risk after a careful ratio.

to Patients with a pheochromocytoma to appoint

bisoprolol only after purpose of therapy blockers of α-adrenoceptors.

Symptoms of a thyrotoxicosis can be disguised by

against the background of administration of drug.

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At use of a bisoprolol the positive take when conducting doping control can be noted.

Use during pregnancy or feeding by a breast. Use of a bisoprolol for pregnant women is possible only with emergency after assessment of a ratio of advantage and risk for mother and a fruit. As a rule, blockers of β-adrenoceptors reduce a blood stream in a placenta and can influence fetation. If treatment by blockers of β-adrenoceptors is necessary, it is desirable that it was β ₁ - a selection blocker of β-adrenoceptors. It is necessary to control a blood stream in a placenta and a uterus. After the delivery the newborn has to be under careful observation. Symptoms of a hypoglycemia and bradycardia can be expected during the first 3 days. There are no data on penetration of a bisoprolol into breast milk. Therefore administration of medicament is not recommended during feeding by a breast.

Ability to influence speed of response at control of vehicles or other mechanisms. In some cases in an initiation of treatment, when replacing medicament and also in interaction with alcohol the ability to drive the car and other mechanisms can be reduced.

Interaction

Contraindicated combinations

Floktafenin: blockers of β-adrenoceptors can aggravate compensatory cardiovascular reactions in connection with arterial hypotension and shock which use of a floktafenin can entail.

Sultoprid: bisoprolol it is not necessary to apply along with sultopridy because of increase in risk of ventricular arrhythmia.

Unrecommended combinations

Lecheniye of chronic heart failure. Antiarrhytmic medicaments I of a class (for example quinidine, Disopyramidum, lidocaine, Phenytoinum, flekainid, propafenon): negative impact on AV conductivity and inotropic function of a myocardium.

All indications. Antagonists of calcium (verapamil, diltiazem, bepridit): negative impact on inotropic function of a myocardium, AV conductivity, ABP. In/in administration of verapamil can lead to the profound arterial hypotension and AV blockade at the patients accepting blockers of β-adrenoceptors.

Hypotensive medicaments of the central action (clonidine, Methyldopum, guanfatsin, moksinidin, rilmenidin): increase in risk of reflex AG and also considerable decrease in ChSS, oppression of AV conductivity, deterioration in heart failure is possible. At combination therapy the sudden cancellation of these medicaments can increase risk of reflex AG.

Combination which should be applied with care

Lecheniye AG or an ischemic heart disease (stenocardia). Antiarrhytmic medicaments I of a class (for example quinidine, Disopyramidum, lidocaine, Phenytoinum, flekainid, propafenon): negative impact on AV conductivity and inotropic function of a myocardium.

All indications. Antiarrhytmic medicaments I of a class (for example quinidine, Disopyramidum, lidocaine, Phenytoinum, flekainid, propafenon): negative impact on AV conductivity and strengthening of negative inotropic effect.

Antagonists of calcium (dihydropyridine derivatives, for example nifedipine, felodipin, amlodipin): can increase risk of developing of arterial hypotension and risk of developing heart failure. The possibility of increase in negative impact on inotropic function of a myocardium at patients with heart failure is not excluded.

Antiarrhytmic medicaments III of a class (for example Amiodaronum): potentiation of influence on AV conductivity is possible.

Blockade of β-adrenoceptors can mask hypoglycemia symptoms.

Insulin and oral antidiabetic means: effect of these medicaments amplifies. Bisoprolol can mask hypoglycemia symptoms. Similar interaction is more probable at use of non-selective blockers of β-adrenoceptors.

Cardiac glycosides (foxglove drugs): reduce ChSS, increase AV conductivity time.

Means for anesthesia: increase risk of oppression of function of a myocardium and development of arterial hypotension.

NPVP: reduce hypotensive effect of a bisoprolol.

β-sympathomimetics (for example izoprenalin, Dobutaminum): the combination with bisoprololy can reduce therapeutic effect of both drugs.

Sympathomimetics which activate α- and β-adrenoceptors (epinephrine, Norepinephrinum), raise the ABP and strengthen the phenomena of the alternating lameness. Similar interaction is more probable at use of non-selective blockers of β-adrenoceptors.

Tricyclic antidepressants, barbiturates, fenotiazina and other antihypertensive drugs: increase risk of hypotension.

: time of AV conductivity can increase and the risk of bradycardia increases.

Resolved combinations

Meflokhin: increase in risk of bradycardia.

MAO Inhibitors (except for MAO inhibitors of V type): increase hypotensive effect of blockers of β-adrenoceptors. There is a risk of developing hypertensive crisis.

Overdose

Symptoms: bradycardia, arterial hypotension, acute heart failure, bronchospasm, hypoglycemia. there is a broad variability of individual sensitivity to a single high dose of a bisoprolol, patients with heart failure can be more sensitive to drug.

in case of overdose needs to see a doctor immediately.

At overdose also recorded cases of development of AV blockade of the III degree and dizziness.

Treatment: to stop administration of medicament and to carry out the supporting and symptomatic treatment. There are limited data that bisoprolol difficult gives in to dialysis.

monitoring of respiratory function; artificial respiration can be shown.

At a bronchospasm: broncholitic medicaments (for example izoprenalin) or β ₂ - adrenomimetik and/or Aminophyllinum.

At AV blockade of II and III degree: infusional introduction of an izoprenalin; in case of need — cardiostimulation.

Aggravation of symptoms in heart failure: in/in administration of diuretics, vazodilatator.

In bradycardia: in/in administration of atropine. If reaction is absent, with care it is necessary to enter izoprenalin or other medicament with positive chronotropic effect. To enter in exceptional cases an artificial pacemaker.

In arterial hypotension: intake of vasoconstrictive medicaments and plasma substitutes, in/in introduction of a glucagon.

At a hypoglycemia: in/in administration of glucose.

Storage conditions

At a temperature not above 25 °C.