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Emcor, Emcor LS (2012)

Contraindications

Bisoprolol is contra-indicated in patients with:

  • acute heart failure or during episodes of heart failure decompensation requiring i.v. inotropic therapy
  • cardiogenic shock
  • second or third degree AV block (without a pacemaker)
  • sick sinus syndrome
  • sinoatrial block
  • bradycardia (heart rate less than 60 beats/min prior to start of therapy)
  • hypotension (systolic blood pressure < 100mmHg)
  • severe bronchial asthma or severe chronic obstructive pulmonary disease
  • severe forms of peripheral arterial occlusive disease and Raynaud’s syndrome
  • untreated phaeochromocytoma (see section 4.4)
  • metabolic acidosis
  • hypersensitivity to bisoprolol or to any of the excipients

Special warnings and precautions for use

Bisoprolol must be used with caution in:

  • Heart failure: The treatment of stable chronic heart failure with bisoprolol has to be initiated with a special titration phase (for details, see SPC for bisoprolol indicated for the treatment of stable chronic heart failure).
  • Bronchospasm (bronchial asthma, obstructive airways diseases): In bronchial asthma or other chronic obstructive lung diseases, which may cause symptoms, bronchodilating therapy should be given concomitantly. Occasionally an increase of the airway resistance may occur in patients with asthma, therefore the dose of beta2-stimulants may have to be increased.

For patients with severe renal impairment and patients with severe liver function disorders please refer to section 4.2.

  • Diabetes mellitus with large fluctuations in blood glucose values; symptoms of hypoglycaemia can be masked.
  • Strict fasting.
  • Ongoing desensitisation therapy.
  • First degree AV block.
  • Prinzmetal’s angina.
  • Peripheral arterial occlusive disease (intensification of complaints might happen especially during the start of therapy)
  • General anaesthesia.

In patients undergoing general anaesthesia beta-blockade reduces the incidence of arrhythmias and myocardial ischemia during induction and intubation, and the post-operative period. It is currently recommended that maintenance of beta-blockade be continued peri-operatively. The anaesthesist must be aware of beta-blockade because of the potential for interactions with other drugs, resulting in bradyarrhythmias, attenuation of the reflex tachycardia and the decreased reflex ability to compensate for blood loss. If it is thought necessary to withdraw beta-blocker therapy before surgery, this should be done gradually and completed about 48 hours before anaesthesia.

Combination of bisoprolol with calcium antagonists of the verapamil or diltiazem type or with centrally acting antihypertensive drugs is generally not recommended, for details please refer to section 4.5.

As with other beta-blockers, bisoprolol may increase both the sensitivity towards allergens and the severity of anaphylactic reactions. Adrenaline treatment does not always give the expected therapeutic effect.

Patients with psoriasis or with a history of psoriasis should only be given beta-blockers (e.g. bisoprolol) after carefully balancing the benefits against the risks.

In patients with phaeochromocytoma bisoprolol must not be administered until after alpha-receptor blockade.

Under treatment with bisoprolol the symptoms of a thyrotoxicosis may be masked.

Treatment with bisoprolol should not be stopped abruptly unless clearly indicated, especially in patients with ischaemic heart disease.

Interaction with other medicinal products and other forms of interaction

Combinations not recommended

Calcium antagonists of the verapamil type and to a lesser extent of the diltiazem type: Negative influence on contractility and atrio-ventricular conduction. Intravenous administration of verapamil in patients on beta-blocker treatment may lead to profound hypotension and atrioventricular block.

Centrally acting antihypertensive drugs such as clonidine and others (e.g. methyldopa, moxonodine, rilmenidine): Concomitant use of centrally acting antihypertensive drugs may further decrease the central sympathetic tonus (reduction of heart rate and cardiac output, vasodilation). Abrupt withdrawal, particularly if prior to beta-blocker discontinuation, may increase risk of “rebound hypertension”.

Combinations to be used with caution

Calcium antagonists of the dihydropyridine type such as nifedipine: Concomitant use may increase the risk of hypotension, and an increase in the risk of a further deterioration of the ventricular pump function in patients with heart failure cannot be excluded.

Class-I antiarrhythmic drugs (e.g. disopyramide, quinidine): Effect on atrio-ventricular conduction time may be potentiated and negative inotropic effect increased

Class-III antiarrhythmic drugs (e.g. amiodarone): Effect on atrio-ventricular conduction time may be potentiated.

Topical beta-blockers (e.g. eye drops for glaucoma treatment) may add to the systemic effects of bisoprolol.

Parasympathomimetic drugs: Concomitant use may increase atrio-ventricular conduction time and the risk of bradycardia.

Insulin and oral antidiabetic drugs: Intensification of blood sugar lowering effect. Blockade of beta-adrenoreceptors may mask symptoms of hypoglycaemia.

Anaesthetic agents: Attenuation of the reflex tachycardia and increase of the risk of hypotension (for further information on general anaesthesia see also section 4.4).

Digitalis glycosides: Reduction of heart rate, increase of atrio-ventricular conduction time.

Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs may reduce the hypotensive effect of bisoprolol.

Beta-sympathomimetic agents (e.g. isoprenaline, dobutamine): Combination with bisoprolol may reduce the effect of both agents.

Sympathomimetics that activate both beta- and alpha-adrenoceptors (e.g. noradrenaline, adrenaline): Combination with bisoprolol may unmask the alpha-adrenoceptor-mediated vasoconstrictor effects of these agents leading to blood pressure increase and exacerbated intermittent claudication. Such interactions are considered to be more likely with nonselective beta-blockers. Higher doses of adrenaline may be necessary for treatment of allergic reactions.

Concomitant use with antihypertensive agents as well as with other drugs with blood pressure lowering potential (e.g. tricyclic antidepressants, barbiturates, phenothiazines) may increase the risk of hypotension.

Moxisylyte: Possibly causes severe postural hypotension.

Combinations to be considered

Mefloquine: increased risk of bradycardia

Monoamine oxidase inhibitors (except MAO-B inhibitors): Enhanced hypotensive effect of the beta-blockers but also risk for hypertensive crisis.

Pregnancy and lactation

Pregnancy

Bisoprolol has pharmacological effects that may cause harmful effects on pregnancy and/or the foetus/newborn. In general, β-adrenoceptor blockers reduce placental perfusion, which has been associated with growth retardation, intrauterine death, abortion or early labour. Adverse effects (e.g. hypoglycaemia and bradycardia) may occur in the foetus and newborn infant. If treatment with β-adrenoceptor blockers is necessary, β1-selective adrenoceptor blockers are preferable.

Bisoprolol should not be used during pregnancy unless clearly necessary. If treatment with bisoprolol is considered necessary, the uteroplacental blood flow and the foetal growth should be monitored. In case of harmful effects on pregnancy or the foetus alternative treatment should be considered. The newborn infant must be closely monitored. Symptoms of hypoglycaemia and bradycardia are generally to be expected within the first 3 days.

Lactation

It is not known whether this drug is excreted in human milk. Therefore, breastfeeding is not recommended during administration of bisoprolol.

Effects on ability to drive and use machines

In a study of coronary heart disease patients, bisoprolol did not impair driving performance. However, due to individual variations in reactions to the drug, the ability to drive a vehicle or to operate machinery may be impaired. This should be considered particularly at the start of treatment and upon change of medication as well as in conjunction with alcohol.

Undesirable effects

The following definitions apply to the frequency terminology used hereafter:

Very common (≥ 1/10)
Common (≥ 1/100, < 1/10)
Uncommon (≥ 1/1,000, < 1/100)
Rare (≥ 1/10,000, < 1/1,000)
Very rare (< 1/10,000)

Cardiac disorders

Uncommon: AV-conduction disturbances, worsening of pre-existing heart failure, bradycardia.

Vascular disorders

Common: feeling of coldness or numbness in the extremities, hypotension.

Uncommon: Orthostatic hypotension.

Metabolism and nutrition disorders

Rare: Increased triglycerides.

Psychiatric disorders

Uncommon: sleep disorders, depression.

Rare: nightmares, hallucinations.

Nervous system disorders

Common: dizziness*, headache*.

Rare: syncope

Eye disorders

Rare: reduced tear flow (to be considered if the patient uses lenses).

Very rare: conjunctivitis.

Ear and labyrinth disorders

Rare: hearing disorders.

Respiratory, thoracic and mediastinal disorders

Uncommon: bronchospasm in patients with bronchial asthma or a history of obstructive airways disease.

Rare: allergic rhinitis.

Gastrointestinal disorders

Common: gastrointestinal complaints such as nausea, vomiting, diarrhoea, constipation.

Hepatobiliary disorders

Rare: increased liver enzymes (ALAT, ASAT), hepatitis.

Skin and subcutaneous tissue disorders

Rare: hypersensitivity reactions (itching, flush, rash).

Very rare: beta-blockers may provoke or worsen psoriasis or induce psoriasis-like rash, alopecia.

Musculoskeletal and connective tissue disorders

Uncommon: muscular weakness and cramps.

Reproductive system and breast disorders

Rare: potency disorders.

General disorders

Common: fatigue*.

Uncommon: asthenia.

* These symptoms especially occur at the beginning of the therapy. They are generally mild and often disappear within 1-2 weeks.

Incompatibilities

None.