BISOCOR Tablet Ref.[49832] Active ingredients: Bisoprolol

Warnings

Especially in patients with ischaemic heart disease the cessation of therapy with bisoprolol must not be done abruptly unless clearly indicated, because this may lead to transitional worsening of heart condition (see section 4.2). ). The initiation of treatment with bisoprolol necessitates regular monitoring. For the posology and method of administration please refer to section 4.2.

Precautions

Bisoprolol must be used with caution in patients with hypertension or angina pectoris and accompanying heart failure.

Bisoprolol must be used with caution in:

• diabetes mellitus showing large fluctuations in blood glucose values. Symptoms of hypoglycaemia (e.g. tachycardia, palpitations or sweating) can be masked.
• strict fasting.
• ongoing desensitisation therapy. As with other beta-blockers, bisoprolol may increase both the sensitivity towards allergens and the severity of anaphylactic reactions. Epinephrine treatment may not always yield the expected therapeutic effect.
• First degree AV block.
• Prinzmetal’s angina.
• peripheral arterial occlusive disease. Aggravation of symptoms may occur especially when starting therapy.

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

The symptoms of thyrotoxicosis may be masked under treatment with bisoprolol.

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

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 anaesthetist must be aware of beta-blockade because of the potential for interactions with other drugs, resulting in bradyarrhythmias, attenuation of reflex tachycardia, and decreased reflex ability to compensate for blood loss. If it is thought necessary to withdraw beta-blocker therapy before surgery, this should be donegradually and completed about 48 hours before anaesthesia.

In bronchial asthma or other chronic obstructive pulmonary diseases, which may cause symptoms, concomitant bronchodilating therapy is recommended. Occasionally an increase of the airway resistance may occur in patients with asthma, therefore the dose of beta2-stimulants may have to be increased.

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Combinations not recommended

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

Negative effect on contractility and atrio-ventricular conduction. Intravenous administration of verapamil in patients on beta-blocker treatment may lead to profound hypotension and atrio-ventricular block.

Centrally-acting antihypertensive drugs (e.g. clonidine methyldopa, moxonodine, rilmenidine)

Concomitant use of centrally-acting antihypertensive drugs may further decrease the central sympathetic tonus and may thus lead to reduction of heart rate and cardiac output and to vasodilatation. Abrupt withdrawal, particularly if prior to beta-blocker discontinuation, may increase the risk of ‘rebound hypertension’.

Combinations to be used with caution

Class-I antiarrhythmic drugs (e.g. quinidine, disopyramide; lidocaine, phenytoin; flecainide propafenone)

Effect on atrio-ventricular conduction time may be potentiated and negative inotropic effect increased.

Calcium antagonists of the dihydropyridine type (e.g. felodipine and amlodipine)

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-III antiarrhythmic drugs (e.g. amiodarone)

Effect on atrio-ventricular conduction time may be potentiated.

Parasympathomimetic drugs

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

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

Insulin and oral antidiabetic drugs

Increase of blood sugar lowering effect. Blockade of betaadrenoceptors 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 section 4.4).

Digitalis glycosides

Increase of atrio-ventricular conduction time, reduction in heart rate.

Non-steroidal anti-inflammatory drugs (NSAIDs)

NSAIDs may reduce the hypotensive effect of bisoprolol.

Beta-sympathomimetics (e.g. isoprenaline, dobutamine)

Combination with bisoprolol may reduce the effect of both agents.

Sympathomimetics that activate both beta- and alpha-adrenoceptors (e.g. norepinephrine, epinephrine)

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.

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.

Combinations to be considered

Mefloquine

Increased risk of bradycardia.

Monoamine oxidase inhibitors (except MAO-B inhibitors)

Enhanced hypotensive effect of the betablockers but also risk of hypertensive crisis.

Rifampicin

Slight reduction of the half-life of bisoprolol possible due to the induction of hepatic drug metabolising enzymes. Normally no dosage adjustment is necessary.

Ergotamine derivatives

Exacerbation of peripheral circulatory disturbances.

Pregnancy

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

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

Lactation

There are no data on the excretion of bisoprolol in human breast milk or the safety of bisoprolol exposure in infants. Therefore, breastfeeding is not recommended during administration of bisoprolol.

In a study with coronary heart disease patients, bisoprolol did not impair driving performance. However, depending on the individual patients response to treatment an effect on the ability to drive a vehicleor to use machines cannot be excluded. This needs to be considered particularly at start of treatment, upon change of medication, or in conjunction with alcohol.

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

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; e-mail: medsafety@hpra.ie.

Not applicable.