BICARDOL

Treatment of stable chronic heart failure with reduced left ventricular systolic function as an adjunct to angiotensin-converting enzyme (ACE) inhibitors and diuretics, and if necessary, digitalis (for further information, see section 5.1).

Not recommended combinations

+ Calcium antagonists of the verapamil type, or, 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.

+ Class I anti-arrhythmic drugs (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone)

The effect on atrioventricular conduction time may be potentiated and the negative inotropic effect increased.

+ Centrally acting antihypertensive drugs such as clonidine and other drugs (e.g. methyldopa, moxonidine, rilmenidine)

Aggravation of heart failure due to a decrease in central sympathetic tone (decrease in heart rate and cardiac output, vasodilation). Abrupt withdrawal of the treatment, particularly if it occurs before the withdrawal of the beta-blocker, may increase the risk of "rebound hypertension".

Combinations requiring 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 with heart failure cannot be excluded.

+ Class III anti-arrhythmic drugs (e.g. amiodarone)

The effect on atrioventricular conduction may be increased.

+ Beta-blockers for local use (e.g. eye drops for the treatment of glaucoma)

The general effects of bisoprolol may be potentiated.

+ Parasympathomimetic drugs

Atrioventricular conduction time and the risk of bradycardia may be increased.

+ Insulin and oral hypoglycemic drugs

Increase in the blood glucose lowering effect. Blockade of beta-adrenoceptors is likely to mask the signs of hypoglycemia.

+ Anesthetics

Attenuation of reflex tachycardia and increase in the risk of hypotension (for further information on general anesthesia see also section 4.4).

+ Digitalis glycosides

Decrease in heart rate, increase in atrioventricular conduction time.

+ Non-steroidal anti-inflammatory drugs (NSAIDs)

The hypotensive action of bisoprolol may be decreased.

+ Beta-sympathomimetic drugs (e.g. isoprenaline, dobutamine)

Combination with bisoprolol may decrease the effect of both drugs.

Sympathomimetic drugs that activate alpha and beta-adrenergic receptors (e.g. noradrenaline, adrenaline)

Combination with bisoprolol may unmask the alpha-adrenergic vasoconstrictor effect of these drugs, leading to hypertension and exacerbation of intermittent claudication.

These interactions are considered more likely with non-selective beta-blockers.

+ Antihypertensive drugs, or drugs that may induce hypotension (e.g. tricyclic antidepressants, barbiturates, phenothiazines)

The risk of hypotension may be increased.

Combinations to be taken into account

+ Mefloquine

Increased risk of bradycardia.

+ Monoamine oxidase inhibitors (except MAO-B inhibitors)

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

Pregnancy

Bisoprolol possesses pharmacological properties likely to cause harmful effects on pregnancy and/or the foetus/newborn. In general, beta-blockers decrease placental perfusion; this effect has been associated with growth retardation, intrauterine deaths, abortions or preterm labour. Adverse effects (for example hypoglycemia and bradycardia) may occur in the foetus and the newborn. If beta-blocker treatment is necessary, beta-1 selective agents should be preferred.

Bisoprolol should not be used during pregnancy except if necessary. If bisoprolol treatment proves necessary, uteroplacental blood flow and foetal growth should be monitored. In case of harmful effects on pregnancy or on the foetus, starting another treatment should be considered.

The newborn should be subject to close monitoring. Symptoms of hypoglycemia and bradycardia generally appear within the first 3 days of life.

Breastfeeding

It is unknown if this medicine is excreted in breast milk. Consequently, breastfeeding is not recommended during administration of bisoprolol.

In a study conducted in patients with ischaemic heart disease, bisoprolol did not impair driving performance. However, due to inter-individual variability in reactions to the medication, the ability to drive vehicles and use machines may be impaired. This effect should be taken into account particularly at the start of treatment, in case of modification of treatment as well as in combination with alcohol.

The frequency terms used below correspond to the following definitions:

Very frequent (≥ 1/10)

Frequent (≥ 1/100 to < 1/10)

Uncommon (≥ 1/1 000 to < 1/100)

Rare (≥ 1/10 000 to < 1/1 000)

Very rare (< 1/10 000)

Frequency unknown (cannot be estimated based on available data)

Cardiac disorders:

Very frequent: bradycardia.

Frequent: worsening of heart failure.

Uncommon: atrioventricular conduction disorders.

Investigations:

Rare: elevation of triglycerides, elevation of liver enzymes (ALAT, ASAT).

Nervous system disorders:

Frequent: dizziness, headache.

Rare: syncope.

Eye disorders:

Rare: dry eyes (to be taken into account if the patient wears contact lenses).

Very rare: conjunctivitis.

Ear and labyrinth disorders:

Rare: hearing disorders.

Respiratory, thoracic and mediastinal disorders:

Uncommon: bronchospasm in patients suffering from asthma or having a history of obstructive airway disorders.

Rare: allergic rhinitis.

Gastrointestinal disorders:

Frequent: gastrointestinal disorders of the type nausea, vomiting, diarrhea, constipation.

Skin and subcutaneous tissue disorders:

Rare: hypersensitivity reactions (pruritus, flush, rash and angioedema).

Very rare: alopecia. Beta-blockers may cause or worsen psoriasis or induce a psoriasiform rash.

Musculoskeletal and connective tissue disorders:

Uncommon: muscle weakness and cramps.

Vascular disorders:

Frequent: sensation of cold or numbness in the extremities, hypotension.

Uncommon: orthostatic hypotension.

General disorders:

Frequent: asthenia, fatigue.

Hepatobiliary disorders:

Rare: hepatitis.

Reproductive system and breast disorders:

Rare: erectile dysfunction.

Psychiatric disorders:

Uncommon: sleep disorders, depression.

Rare: nightmares, hallucinations.

Reporting of suspected adverse effects

Reporting suspected adverse effects after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals report any suspected adverse effect via the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and the network of Regional Pharmacovigilance Centres - Website: www.signalement-sante.gouv.fr .