Treatment of hypertension

Treatment of chronic angina, stable.

Treatment of heart failure, stable chronic with decreased ventricular function, left systolic in addition to enzyme inhibitors, conversion (IEC) and diuretics, and possibly digitalis (for further information, See section Pharmacodynamic properties).

Administration

Oral use.

Bisoprolol Accord Healthcare should be taken in the morning and can be taken with food. The tablets must be swallowed whole with a glass of water, without being chewed.

Treatment of hypertension and chronic stable angina

Adults

The dosage should be adjusted on a case-by-case basis. The recommended starting dose is 5 mg daily. The usual dose is 10 mg once daily and the recommended maximum dose is 20 mg per day.
Patients with renal insufficiency

In patients with severe renal insufficiency (creatinine clearance
Stop processing

Treatment should not be interrupted suddenly (see section CAUTIONS AND PRECAUTIONS FOR USE). The dosage should be gradually decreased by reducing the dose by half each week.


Adults

The standard treatment for chronic heart failure consists of an ACE inhibitor (or an inhibitor, angiotensin receptor for intolerance, ACE inhibitors), a beta-blocker, diuretics and, where appropriate, Cardiac glycosides. Patients should be stable (without acute episode) at the initiation of bisoprolol treatment.



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 a day 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 following 4 weeks, if the drug is well tolerated, increase to

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

10 mg once daily in treatment, maintenance.

The maximum recommended dose is 10 mg once daily.
Monitoring of vital constants (heart rate, blood pressure) and symptoms of aggravation of heart failure is recommended during the titration period. Symptoms may already occur from the first day after initiation of treatment.
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 or older with mild to moderate chronic heart failure (NYHA Class II or III) and a left ventricular ejection fraction ≤ 35%, previously not receiving IEC, beta-blockers or angiotensin antagonists Patients were treated with bisoprolol and enalapril for 6 to 24 months after treatment Initial of 6 months by 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.

Hypertension or angor

Bisoprolol is used for the treatment of hypertension and angina. As with other beta-blockers, the mode of action of the drug in hypertension is not currently elucidated. It is known, however, that bisoprolol considerably reduces the activity of plasma renin.

Mechanism of action: antianginal: by blocking receptors, beta-adrenergic cardiac, bisoprolol inhibits the response to sympathetic activation. This leads to a decrease in heart rate and contractility, which reduces the oxygen demand of the cardiac muscle.

In acute administration in patients with ischemic heart disease without chronic heart failure, bisoprolol decreases heart rate and ejection volume, systolic, and thus cardiac output and oxygen consumption. In chronic administration, peripheral resistances, initially high, decrease.

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 suffering from chronic cardiac insufficiency with the following problems:

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

· Cardiogenic shock.

· Atrioventricular block of the second or third degree (not paired).

· Sinus disease.

· Sino-atrial block.

· Symptomatic bradycardia.

· Symptomatic hypotension.

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

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

· Untreated pheochromocytoma (see Warnings and Precautions for Use)

· Metabolic acidosis.

· Hypersensitivity to bisoprolol or any of the excipients (see section Composition).
Warnings, special

Concerning only chronic cardiac insufficiency

The introduction of stable chronic heart failure therapy with bisoprolol requires a special titration phase (see section 4.2).
Concerning all the indications

In patients suffering in particular from ischemic heart disease, discontinuation of bisoprolol therapy should not be carried out suddenly unless otherwise indicated, as this may lead to a temporary worsening of heart disease (see section Dosage And mode of administration).

Precautions for use

Concerning only hypertension or angina

Bisoprolol Accord; Healthcare should be used with caution in patients with hypertension or angina and also with heart failure.


The introduction of bisoprolol treatment should be accompanied by regular surveillance. For the dosage and mode of administration, please refer to the section Posology and method 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 insufficiency

· Severe hepatic impairment

· Restrictive cardiomyopathy.

· Congenital heart disease.

· An organ valvular pathology with a significant hemodynamic significance

· Myocardial infarction less than 3 months old

Concerning all the indications

Bisoprolol Accord Healthcare should be used with caution in case of

· Bronchospasm (asthma, obstructive airway diseases).

· Diabetes with significant fluctuations in blood glucose, symptoms of hypoglycemia may be masked

· Strict fasting

· Desensitization treatment in progress.

· 1st degree atrioventricular block.

· Prinzmetal angina.

Occlusive peripheral arterial disturbances (an increase in symptoms may be observed, especially at the beginning of treatment)

In patients receiving general anesthesia, beta-blockers reduce the incidence of arrhythmias and myocardial ischemia during induction and intubation, as well as during the post-operative period. It is currently recommended to continue treatment with beta-blockers during the perioperative period. The anesthesiologist should be cautioned about taking beta-blocker because of its potential for interactions with other drugs, leading to bradyarrhythmias, decreased reflex tachycardia and decreased reflex Compensation in case of blood loss. If discontinuation of beta-blocker therapy is deemed necessary prior to surgery, this should be stopped and terminated approximately 48 hours before anesthesia. >
Beta-blockers (such as bisoprolol) can not be prescribed to patients with psoriasis or a history of psoriasis unless they have carefully evaluated the benefits and risks of such treatment in these patients.

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

Treatment with bisoprolol may mask the symptoms of thyrotoxicosis

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 contraindicated

Concerning only heart failure, chronic

+; Class I antiarrhythmic drugs (eg, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone)

The effect on the atrio-ventricular conduction time can be potentiated and the negative inotropic effect can be increased

Concerning all the indications

+ Calcium antagonists of the verapamil type and to a lesser extent of the diltiazem type

Negative effect on contractility and atrioventricular conduction Intravenous administration of verapamil in patients on beta-blockers may induce severe hypotension and atrioventricular block
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+ Centrally acting antihypertensive drugs such as clonidine and others (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

Concerning only hypertension or angina

+; Class I antiarrhythmic drugs (eg, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone)

The effect on the atrio-ventricular conduction time can be potentiated and the negative inotropic effect can be increased

Concerning all the indications

+ 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

+ 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

Hypoglycaemic effect. 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.

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

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

Sympathomimetic drugs that activate α- and β-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.

+ Antihypertensives or medicinal products that can 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

+; Rifampicin

Slight decrease in the half-life of bisoprolol due to the induction of hepatic enzymes involved in drug metabolism. Normally no dose adjustment is required.
+; Derivatives of ergotamine

Exacerbation of circulatory disorders, peripheral.

Without object.

In general, the most common signs encountered in overdosage of a beta-blocker are bradycardia, hypotension, bronchospasm, acute heart failure, and hypoglycaemia. To date, some cases of overdosage (maximum 2000 mg) with bisoprolol have been reported in patients with hypertension and / or ischemic heart disease and have been shown to be 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 solutions and vasopressors should be administered. Intravenous glucagon may be useful.

Atrioventricular block (2nd or 3rd degree): Patients should be carefully monitored and treated with isoprenaline infusion or laying a pacemaker, if applicable
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Acute aggravation of heart failure: administration of diuretics, 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

The limited data available suggests 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 selective beta-1 agents.

Bisoprolol should not be used during pregnancy unless needed. 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 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.

Within each group frequency, undesirable effects should be presented in order of decreasing severity.
The following definitions apply to the terminology used to describe the frequency of undesirable effects

Very common (≥ 1/10)

Common (≥ 1/100,