Treatment of stable chronic heart failure with reduction of left ventricular systolic function in addition to inhibitors of the conversion enzyme (ACE) and diuretics, and possibly digitalis (for further information, See section “Pharmacodynamic properties”.)
The standard treatment for chronic heart failure consists of an ACE inhibitor (or an angiotensin receptor inhibitor in case of intolerance to ACE inhibitors), a beta-blocker, Diuretics and the case of cardiac glucosides. Patients should be stable (without acute episode) at the initiation of bisoprolol treatment.
It is recommended that treatment be provided by a treating physician with experience in the management of patients with chronic heart failure

Transient aggravation of heart failure, hypotension or bradycardia may occur during the titration period and thereafter.

Titration period

The introduction of the treatment of stable chronic heart failure by bisoprolol requires a titration period

Treatment with bisoprolol should begin at progressive doses, according to the following steps

1.25 mg once daily for 1 week, if the drug is well tolerated, increase to

· 2.5 mg once daily for another week, if the drug is well tolerated, increase to

3.75 mg once a day for another week, if the drug is well tolerated, increase to

5 mg once daily for the next 4 weeks, if the drug is well tolerated, increase to

· 7.5 mg once daily for the next 4 weeks, if the drug is well tolerated, increase to

· 10 mg once daily in maintenance treatment

The recommended maximum dose is 10 mg once daily.
Modification of processing

If the maximum recommended dose is not well tolerated, a gradual reduction in the dose may be considered.

In the event of transient aggravation of heart failure, hypotension or bradycardia, the dosage of concomitant therapies should be reviewed. It may also be necessary to temporarily reduce the dose of bisoprolol or to consider stopping the treatment. The resumption of treatment and / or the increased dose of bisoprolol should be systematically considered once the patient is stable again. If the discontinuation of treatment is contemplated, a gradual reduction of the dose is recommended because a sudden interruption could result in acute degradation of the patient's condition.
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The treatment of heart failure, stable chronic by bisoprolol is usually a long-term treatment.


Bisoprolol tablets should be taken in the morning, before, during or after breakfast, should be swallowed with a little liquid, and should not be chewed.

Special Populations

Renal or hepatic impairment

No data are available concerning the pharmacokinetics of bisoprolol in patients with hepatic or renal impairment who have chronic cardiac insufficiency and the increase in dosage should therefore be carried out with even greater caution in these patients.

Elderly patients

It is not necessary to adapt the dosage.

Children

Since no data are available with pediatric bisoprolol, its use can not be recommended in children

Tablet beige, round, convex, bare, with a scored bar on both sides.

On one of the faces are engraved on either side of the score bar, the words "BI" and "10".

The tablet can be divided into two equal half-doses.

Class: Pharmacotherapeutic: beta-blocker, selective, ATC code: C07AB07

Bisoprolol is a beta-blocker with a high affinity for β-1 receptors, without sympathomimetic activity, intrinsic, nor membrane stabilizing effect. It has only a weak affinity for the beta-2 receptors of the smooth muscles of the bronchi and the vessels and for the beta-2 receptors involved in metabolic regulation. As a result, bisoprolol generally does not alter the resistance of the airways and has no metabolic effects related to the action on the beta-2 receptors. The beta-1 selectivity of bisoprolol extends beyond the therapeutic doses

A total of 2,647 patients were enrolled in the CIBIS II study. 83% (n = 2202) were in class III of NYHA and 17% (n '= 445) in NYHA class IV. They had stable systolic cardiac insufficiency (fraction, ejection ≤ 35%, based on echocardiography). Total mortality decreased from 17.3% to 11.8% (relative decrease of 34%).
A decrease in the frequency of sudden deaths (3.6% versus 6.3%, a relative decrease of 44%) and a reduction in episodes of heart failure requiring hospitalization (12% versus 17 , 6%, relative decrease of 36%) were observed.
Finally, a significant improvement in functional status according to the classification, NYHA was observed.

During initiation and titration, doses of bisoprolol, hospitalizations for bradycardia (0.53%), hypotension (0.23%) or acute decompensation (4.97%) were observed; Were not more frequent than in the placebo group (0%, 0.3% and 6.74%, respectively). The number of fatal or disabling strokes in the total study duration was 20 in the bisoprolol group and 15 in the placebo group.

The CIBIS III study included 1010 patients aged ≥ 65 years with mild to moderate chronic heart failure (NYHA class II or III) and a ventricular ejection fraction ≤ 35%, having previously received no angiotensin converting enzyme inhibitors, β-blockers or antagonists. Patients were treated with the combination of bisoprolol and enalapril for 6-24 months after an initial 6-month treatment with either bisoprolol or enalapril. >

There was a higher frequency of aggravation of chronic heart failure when bisoprolol was used in the initial 6-month treatment. The non-inferiority between the initial treatment with bisoprolol and the initial treatment with enalapril has not been proved in the per-protocol analysis, although both strategies for initiating the treatment of Heart failure showed a similar rate in the frequency of the composite primary endpoint of deaths and hospitalizations at the end of the study (32.4% in the first group treated with bisoprolol versus 33.1% In the group initially treated with enalapril for the per-protocol population.) The study shows that bisoprolol can also be used in elderly patients with chronic heart failure in its weak form Moderate.

Bisoprolol is also used in the treatment of hypertension, arterial and angina.


In a study in patients with coronary artery disease, bisoprolol did not alter the driving abilities. However, due to individual variations in drug reactions, an effect on the ability to drive and use machines can not be ruled out. This effect shall be taken into account, in particular at the beginning of treatment, in the case of a change in the treatment and in the case of association with alcohol. >
Bisoprolol is contraindicated in the following cases

· Acute heart failure or episodes of decompensation of heart failure, requiring intravenous inotropic treatment

· Cardiogenic shock

· Atrioventricular blocks of the 2nd and 3rd degrees (not paired)

· Sinus disease

· Sino-atrial block

· Symptomatic bradycardia

· Symptomatic hypotension

· Severe bronchial asthma, or broncho-pneumopathies, chronic obstructive in their severe forms

Occlusive peripheral arterial disorders and Raynaud's phenomenon in their severe forms

· Untreated pheochromocytoma (see Warnings and Precautions)

· Metabolic acidosis

Bisoprolol tablets are contraindicated in patients with hypersensitivity to bisoprolol or to any of the excipients (see section Composition)
Warnings, special

The treatment of chronic heart failure controlled by bisoprolol should begin with a specific titration period (see Dosage and Mode of Administration).
Treatment with bisoprolol should not be abruptly discontinued, particularly in patients with ischemic heart disease unless there is a formal indication. Sudden arrest may cause transient aggravation of angina (see section 4.2).


In controlled cardiac insufficiency, the introduction of bisoprolol treatment requires regular monitoring. For the dosage and mode of administration, see Dosage and mode of administration.

No data are currently available on the treatment of heart failure by bisoprolol in patients with the following conditions and conditions

· Insulin-dependent diabetes (type I)

· Severe renal impairment

· Severe hepatic impairment

· Restrictive cardiopathy

· Congenital heart disease

· Organic valvular pathology having a significant hemodynamic significance

· Myocardial infarction less than 3 months old

Bisoprolol should be used with caution in the following cases

· Diabetes with significant blood glucose fluctuations, symptoms of hypoglycemia that can be masked (eg tachycardia, palpitations or sweating)

· Fast strict

· Desensitization treatment in progress. Like other beta-blockers, bisoprolol may increase susceptibility to allergens and the intensity of anaphylactic reactions. Treatment with adrenaline does not always produce the expected therapeutic effect.


· Prinzmetal angina

• Occlusive peripheral arterial disorders • A worsening of symptoms may occur especially during initiation of treatment

Patients with psoriasis or a history of psoriasis should be treated with beta-blockers (eg bisoprolol) only after careful evaluation of the benefits and risks.

Symptoms of thyrotoxicosis may be masked when treated with bisoprolol

In patients with pheochromocytoma, bisoprolol should not be administered prior to alpha-blocking therapy.

In patients under general anesthesia, beta-blocker decreases the incidence of arrhythmias and myocardial ischemia during induction of anesthesia, intubation and post-operative period. It is currently recommended to continue beta-blocker treatment during the period of surgery The anesthesiologist should be advised of taking beta-blocker therapy because of its potential, Other medications, resulting in brady-arrhythmias, decreased tachycardia, reflex and reflex capacity of compensation in case of blood loss. If discontinuation of beta-blocker therapy appears to be necessary, prior to surgery the stop should be phased out and terminated approximately 48 hours before anesthesia. Br>
In asthma or other obstructive chronic bronchopneumopathies, which may become symptomatic, a bronchodilator treatment may be administered concomitantly. Increased airway resistance sometimes occurs in patients with asthma, the dose of beta-2-stimulants should then be increased.


This medicine contains lactose and is not recommended for use in cases of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome (rare hereditary diseases).

Associations, deprecated

Anti-arrhythmics class I (eg quinidine, disopyramide, lidocaine, phenytoin, fleakide, propafenone)
The effect on the conduction time, atrio-ventricular may be potentiated and the negative inotropic effect increased.

+ Calcium antagonists of verapamil type or, to a lesser extent, diltiazem type

Effect, negative on contractility and conduction, atrio-ventricular. Intravenous administration of verapamil in patients on beta-blockers may induce severe hypotension and atrioventricular block.


Aggravation of heart failure, decreased sympathetic central tone (decreased frequency and cardiac output, vasodilatation), abrupt cessation of treatment, especially if it occurs, before discontinuation of beta- Blocker, may increase the risk of "hypertension rebound".
Associations subject to precautions for use

+ Calcium antagonists of the dihydropyridine type (such as felodipine and amlodipine)

In concomitant use, an increased risk of hypotension and risk of deterioration of ventricular function in patients with heart failure can not be excluded.
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+; Anti-arrhythmic class III (eg amiodarone)

The effect on the conduction time, atrioventricular can be increased.

+; Parasiympathomimetic drugs

Concomitant use may increase the duration of atrioventricular conduction and the risk of bradycardia.
+ Beta-blockers of local use (eg eye drops for the treatment of glaucoma)

The general effects of bisoprolol may be potentiated

+; Insulin and oral antidiabetic drugs

Hypoglycaemic effect. Blocking of beta-adrenergic receptors may mask symptoms of hypoglycemia

+; Anesthetics |
Reduced tachycardia, reflex and increased risk of hypotension (for more information on general anesthesia, see Warnings and Precautions).

+ Cardiovascular glucosides

Increased conduction time, atrioventricular, decreased frequency, heart rate

+ Non-steroidal anti-inflammatory drugs (NSAIDs)

NSAIDs may reduce the action: bisoprolol hypotensive.

+; Β-sympathomimetic drugs (eg, isoprenaline, dobutamine)

The combination with bisoprolol may decrease the effect of both drugs.

+ Sympathomimetic drugs that activate β- and α-adrenergic receptors (eg, noradrenaline, adrenaline)

The association with bisoprolol may reveal the vasoconstrictive, α-adrenergic effect of these drugs, leading to hypertension and aggravation of intermittent claudication. These interactions are considered as more likely with non-selective beta-blockers.

Concomitant use of antihypertensives, as well as other drugs that may induce hypotension (eg, antidepressants, tricyclics, barbiturates, phenothiazines) may increase the risk of hypotension. >

Associations to be taken into account

+; Mefloquine

Increased risk of bradycardia

+; Monoamine oxidase inhibitors (except MAO-B)

Increase in hypotensive effect of beta-blockers, but also risk of hypertensive crisis

+; Rifampicin

A slight decrease in the half-life of bisoprolol is possible due to the induction of metabolic, hepatic enzymes. Generally, no dosage adjustment is necessary.


Exacerbation of circulatory disorders, peripheral.

Without object.

The most frequent signs of overdosage with bisoprolol are bradycardia, hypotension, bronchospasm, acute heart failure and hypoglycemia The experience with bisoprolol in overdosage is limited , Only a few cases have been reported. Cases of bradycardia and / or hypotension have been noted. All patients recovered. There is significant inter-individual variability in sensitivity to a single high dose of bisoprolol and patients with cardiac insufficiency are probably very sensitive. >
In general, in case of overdose, treatment with bisoprolol should be discontinued and symptomatic treatment should be instituted.
In view of the pharmacological actions planned and the recommendations made for the other beta-blockers, the following general measures should be considered when they are clinically justified:

Bradycardia: administration of atropine, I.V. If the response is inadequate, isoprenaline or another drug with positive chronotropic properties may be given with caution. Under certain circumstances, the installation of a pacemaker may be necessary.

Hypotension: intravenous solutions and vasopressors should be administered. Intravenous glucagon may be useful.

Atrioventricular block (2nd or 3rd degree): Patients should be monitored carefully and treated with isoprenaline infusion or pacemaker, if applicable. >

Acute worsening of heart failure: administering I.V., diuretics, inotropic agents, vasodilators.

Bronchospasm: administration of a bronchodilator treatment, such as isoprenaline, sympathomimetic beta-2 drugs and / or aminophylline.

Hypoglycemia: administration, by I.V. route of glucose

Limited data suggest that bisoprolol is difficult to dialyze

Pregnancy

Bisoprolol has pharmacological properties which may cause adverse effects on pregnancy and / or the fetus / newborn. In general, beta-blockers decrease placental perfusion, this effect has been associated with delayed growth, death, intrauterine, abortion or early labor. Adverse effects (eg, hypoglycemia and bradycardia) may occur in the fetus, and the newborn. If treatment with beta-blockers is necessary, preference should be given to β1-selective agents.

Bisoprolol should not be used during pregnancy unless absolutely necessary. If bisoprolol treatment is required, blood flow, utero-placenta and fetal growth should be monitored. In case of adverse effects on pregnancy or the fetus, consideration should be given to starting another treatment. The newborn should be closely monitored. Symptoms of hypoglycaemia and bradycardia usually occur in the first 3 days of life

Breastfeeding

There are no data on the passage of bisoprolol into breast milk or on the safe use of exposure to bisoprolol in infants. Therefore, breast-feeding is not recommended during the administration of bisoprolol.
The frequency terms used hereinafter correspond to the following definitions:

Very common (³ 10%)

Common (³ 1% and