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 is composed of an ACE inhibitor (or an angiotensin receptor inhibitor in case of intolerance to ACE inhibitors), a beta-blocker , Diuretics and, where appropriate, cardiac glycosides. Patients should be stable (without acute episode) at the initiation of treatment with bisoprolol.



Dosage

Titration period

The treatment of heart failure, stable chronic by bisoprolol requires a titration period.

The dosage should be gradually increased, as follows

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 case of transient aggravation of heart failure, hypotension or bradycardia, it is recommended to review the dosage of concomitant treatments. It may also be necessary to temporarily reduce the dose of bisoprolol or to consider discontinuing treatment.

Resumption of therapy and / or increased dose of bisoprolol should be systematically considered as soon as the patient is stable again.
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%, who had previously received no ACE inhibitors, beta blockers or angiotensin antagonists. The patients were treated with the combination of bisoprolol and enalapril for 6 to 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 ischemic heart disease, bisoprolol did not alter driving abilities. However, because of the inter-individual variability of drug reactions, the ability to drive, vehicles and use machines can be altered. This effect shall be taken into account, in particular at the beginning of treatment, in the case of alteration of the treatment and in the case of association with alcohol.
Bisoprolol is contraindicated in patients with chronic heart failure in the following cases

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

· Cardiogenic shock

· Atrio-ventricular blocks of the 2nd and 3rd degrees

· Sinus disease

· Sino-atrial block

· Symptomatic bradycardia

· Symptomatic hypotension

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

· Severe forms of arterial disorders, occlusive peripheral or severe forms of the phenomenon of Raynaud

· Untreated pheochromocytoma (see section Warnings and Precautions for Use)

· Metabolic acidosis

· Hypersensitivity to bisoprolol or to any of the excipients listed under

Initiation and discontinuation of bisoprolol treatment require regular monitoring.

No data is 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 cardiomyopathy

· 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

· Bronchospasm (asthma, obstructive airway diseases)

· Diabetes with significant fluctuations in blood sugar, symptoms of hypoglycemia, can be masked

· 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 • Worsening of symptoms may occur, especially at the beginning of treatment.

· General anesthesia: 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 therapy 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, stop should be phased out and completed 48 hours before anesthesia. >
The combination of bisoprolol with calcium antagonists of the verapamil or diltiazem type, with class I antiarrhythmics, and with centrally acting antihypertensives is generally not recommended (for more anti- Information, refer to the section Interactions with other drugs and other forms of interactions)

In asthma or other obstructive chronic bronchopneumopathies, which may become symptomatic, a bronchodilator treatment may be administered concomitantly. In patients with asthma, an increase in airway resistance may occur requiring an increase in the dose of beta-2 stimulants.


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

Symptoms of thyrotoxicosis may be masked when treated with bisoprolol

Sportsmen

The attention of athletes is drawn to the fact that this specialty contains an active ingredient which can induce a positive reaction of the tests carried out during the antidoping tests. Code>
Associations deprecated

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

Negative effect on contractility and atrioventricular conduction Intravenous administration of verapamil in patients with beta-blockers may induce severe hypotension and atrioventricular block
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Anti-arrhythmics class I (eg quinidine, disopyramide, lidocaine, phenytoin, flecanid, propafenone)
The effect on conduction time, atrioventricular may be potentiated and the negative inotropic effect increased.

+; Central anti-hypertensives such as clonidine and others; drugs (eg methyldopa, moxonidine; rilmenidine)
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

An increase in the risk of hypotension and the risk of deterioration of ventricular function in patients suffering from heart failure can not be excluded

+; Anti-arrhythmic class III (eg amiodarone)

The effect on atrio-ventricular conduction can be increased.
+ Beta-blockers of local use (eg eye drops for the treatment of glaucoma)

The general effects of bisoprolol may be potentiated

+; Parasiympathomimetic drugs

Conduction time, atrioventricular and risk of bradycardia may be increased.
+; Insulin and oral hypoglycaemic drugs

Increased effect, hypoglycaemic. Blockade of beta-adrenoceptors is likely to mask the signs of hypoglycemia.

+; Anesthetics |
Reduced tachycardia, increased reflexes and increased risk of hypotension (for more information on general anesthesia, see also Warnings and Precautions)
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+ Digital;
Decreased frequency, cardiac, increased conduction time, atrioventricular.

+ Non-steroidal anti-inflammatory drugs (NSAIDs)

The hypotensive action of bisoprolol may be decreased.

+ B -sympathomimetic drugs (eg, isoprenaline, dobutamine)

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

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

The combination with bisoprolol may reveal the α-adrenergic vasoconstrictor effect of these drugs, leading to hypertension and aggravation of intermittent claudication.

These interactions are considered more likely with non-selective beta-blockers.
Anti-hypertensives, or medicinal products that may induce hypotension (eg tricyclic antidepressants, barbiturates, phenothiazines)

The risk of hypotension may be increased.

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

Not applicable.

Following an overdose (eg, a daily dosage of 15 mg instead of 7.5 mg), a 3rd degree atrioventricular block, bradycardia and dizziness were reported. >

In general, the most common signs of overdosage of a beta-blocker are bradycardia, hypotension, bronchospasm, acute heart failure, and hypoglycaemia. To date, some cases of overdosage (maximum 2 000 mg) with bisoprolol have been reported in patients with hypertension and / or ischemic heart disease and have resulted in bradycardia and / or hypotension . All patients recovered. There are wide inter-individual variations in sensitivity to a single, high dose of bisoprolol and patients with cardiac insufficiency are probably very sensitive.
In case of overdose, treatment with bisoprolol should be discontinued and symptomatic treatment should be administered. Limited data suggest that bisoprolol is poorly dialyzable. In view of the pharmacological actions planned and the recommendations for the other beta-blockers, the following general measures shall be considered when justified at the clinical level:
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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 fluids and vasopressors should be administered. Intravenous glucagon may be useful.

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

Acute aggravation of heart failure: administration of inotropic agents, vasodilators by I.V.

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

Hypoglycemia, glucose I.V. administration

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 selective beta-1 agents.

Bisoprolol should not be used during pregnancy unless needed. If treatment with bisoprolol 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 must be closely monitored. Symptoms of hypoglycaemia and bradycardia usually occur in the first 3 days of life

Breastfeeding

It is not known whether this drug is excreted in human milk. Therefore, breast-feeding is not recommended during the administration of bisoprolol.


Very common (≥; 1/10)

Common (≥ 1/100,