PRESESE Film-coated tablet Ref.[115297] Active ingredients: Bisoprolol

PRESESE must be used with caution in:

• Concomitant treatment with inhalation anaesthetics
• diabetes mellitus with large fluctuations in blood glucose values; symptoms of hypoglycaemia can be masked, and responses to hypoglycaemia are diminished
• strict fasting

PRESESE must be used with caution in fasting patients.

• ongoing desensitisation therapy
• AV block of first degree
• Prinzmetal's angina. Beta-blockers, including PRESESE, may increase the number of chest pain attacks in patients who have Prinzmetal's angina.
• peripheral arterial occlusive disease (intensification of complaints might happen especially during the start of therapy). PRESESE may aggravate the symptoms of peripheral arterial occlusive disease (PAOD) or Raynaud's syndrome (due to unopposed arteriolar alpha-sympathetic activation). Severe peripheral vascular disease and even peripheral gangrene may be precipitated.

There is no therapeutic experience of PRESESE treatment in heart failure, in patients with the following diseases and conditions:

• NYHA class II heart failure
• insulin dependent diabetes mellitus (Type I)
• impaired renal function (serum creatinine <80 ml/min)
• impaired liver function
• patients older than 80 years
• restrictive cardiomyopathy
• congenital heart disease
• haemodynamically significant organic valvular disease
• myocardial infarction within 3 months β-blockers, such as PRESESE, may cause bronchospasm in patients with asthma (see section 4.3). Bisoprolol may increase both the sensitivity towards allergens and the severity of anaphylactic reactions. Epinephrine (adrenaline) treatment does not always give the expected therapeutic effect.

Psoriasis may be aggravated by PRESESE and therefore must only be given PRESESE after careful consideration of the risks and benefits. The symptoms of thyrotoxicosis may be masked under treatment with PRESESE.

Initiation of treatment with PRESESE necessitates regular monitoring. The cessation of therapy with PRESESE should not be done abruptly unless clearly indicated. Patients should be advised to limit the extent of their physical activity during the period in which PRESESE is being discontinued. In patients undergoing general anaesthesia beta-blockade reduces the incidence of arrhythmias and myocardial ischaemia during induction and intubation, and the postoperative period. The anaesthetist must be aware of beta-blockade because of the potential for interactions with other medicines, resulting in bradydysrhythmias, attenuation of the reflex tachycardia and the decreased reflex ability to compensate for blood loss.

A patient's normal tachycardiac response to hypovolaemia or blood loss may be obscured during or after surgery. Particular caution should be taken in this regard. In the event of surgery, the anaesthetist should be informed of therapy with PRESESE prior to any operation. If the decision is made to withdraw PRESESE before anaesthesia, at least 48 hours should be allowed to elapse between the last dose and surgery. If the medicine is to be continued, care should be taken when using halogenated anaesthetics. Atropine (1 – 2 mg IV) may be used to correct vagal dominance. The patient must be maintained on their usual dosage peri-operatively. In the peri-operative period it is generally unwise to reduce the dosage to which the patient is accustomed, as there may be danger of aggravation of angina pectoris or hypertension.

In patients suffering from ischaemic heart disease, treatment should not be discontinued abruptly. The dosage of PRESESE should be adjusted in severe renal impairment.

Care should be taken in prescribing PRESESE together with Class 1 antidysrhythmic medicines such as disopyramide, myocardial depressants and inhibitors of AV conduction such as calcium antagonists. Caution should be exercised when transferring a patient from clonidine, as the withdrawal of clonidine may result in the release of large amounts of catecholamines that may give rise to a hypertensive crisis. If PRESESE is administered in these circumstances, the unopposed alpha receptor stimulation may potentiate this effect.

If PRESESE and clonidine are given concurrently the clonidine should not be discontinued until several days after the withdrawal of PRESESE, as severe rebound hypertension may occur.

PRESESE should be used with caution in combination with verapamil in patients with impaired ventricular function. This combination should not be given to patients with conduction abnormalities.

Neither medicine should be administered intravenously within 48 hours of discontinuing the other. The intravenous administration of calcium antagonists and antidysrhythmic medicines is not recommended during therapy with PRESESE. The intravenous administration of verapamil in patients on treatment with PRESESE may lead to profound hypotension and atrioventricular block. PRESESE modifies the tachycardia associated with hypoglycaemia.

Patients with phaeochromocytoma usually require treatment with an alpha-adrenergic blocker. PRESESE may increase both the sensitivity towards allergens and the severity of anaphylactic reactions. Adrenaline treatment does not always give the expected therapeutic effect. PRESESE may mask the symptoms of hyperthyroidism.

The normal dose should be reduced in elderly patients, or in patients suffering from renal dysfunction. A patient's normal tachycardiac response to hypovolaemia or blood loss may be obscured during or after surgery. Particular caution should be taken in this regard.

Cases of coronary vasospasm have been observed. Despite its high beta1-selectivity, angina attacks cannot be completely excluded when PRESESE, is administered to patients with Prinzmetal's angina. Utmost caution must be exercised.

Treatment with PRESESE must not be withdrawn abruptly unless clearly indicated (see section 4.2).

Abrupt discontinuation of therapy with PRESESE may cause exacerbation of angina pectoris in patients suffering from ischaemic heart disease, myocardial infarction, ventricular dysrhythmias and in some cases could lead to sudden death.

Discontinuation of PRESESE should be gradual over a period of 1 to 2 weeks, and patients should be advised to limit the extent of their physical activity during the period that PRESESE is being discontinued.

Caution is warranted when treating patients with hypertension or angina pectoris and concomitant heart failure with PRESESE.

Digitalisation of patients receiving long-term beta-blocker therapy including PRESESE may be necessary if congestive cardiac failure is likely to develop. This combination can be considered despite the potentiation of the negative chronotropic effect of the two medicines. Careful control of dosages, and of the individual patient's response (and notably pulse rate), is essential in this situation.

Beta-blockers, including PRESESE, may unmask myasthenia gravis. Although cardioselective (beta1) beta-blockers may have less effect on lung function than nonselective beta-blockers, these should be avoided in patients with obstructive airways diseases, unless there are compelling clinical reasons for their use. Where such reasons exist, PRESESE may be used with caution. 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.

Paediatric population

Safety and efficacy in children have not been established.

It can be dangerous to administer PRESESE with the following medicines:

• Concomitant use of PRESESE with hypoglycaemic medicines, phenothiazines and various antidysrhythmic medicines can have life-threatening consequences, e.g.
  • profound hypoglycaemia with oral hypoglycaemic medicines and insulin;
  • myocardial depression with antidysrhythmic medicines.
• Beta-adrenoceptor stimulating medicines (e.g. isoprenaline, dobutamine) may antagonise the effects of PRESESE. Combination with PRESESE may reduce the effect of both medicines. Higher doses of epinephrine (adrenaline) may be necessary for treatment of allergic reactions.
• Sympathomimetics that activate both beta- and alpha-adrenoceptors (e.g. norepinephrine(noradrenaline), epinephrine (adrenaline)): Combination with PRESESE may unmask the alpha-adrenoceptor-mediated vasoconstrictor effect of these medicines leading to blood pressure increase and exacerbated intermittent claudication.
• Alpha-adrenoceptor stimulants can dangerously affect the vasoconstrictor effects and adrenergic neuron blocking medicines may lead to life-threatening vasoconstriction when used in combination with PRESESE.
• PRESESE and digoxin may be used concomitantly for patients with congestive heart failure provided that the pulse rate and patient response is monitored. It can be dangerous to administer PRESESE with digoxin which can lead to a reduction of heart rate and an increase of atrio-ventricular conduction time.
• Dihydropyridine-type calcium antagonists such as nifedipine and amlodipine, should not be used in combination with PRESESE since this may increase the risk of hypotension. In patients with heart failure, an increase in the risk of further deterioration of the ventricular pump function cannot be excluded.
• Atrio-ventricular conduction time, as well as negative inotropic effect, may be increased when PRESESE is used concurrently with Class-I antidysrhythmic medicines (e.g. disopyramide and quinidine, lidocaine, phenytoin, flecainide, propafenone). Atrioventricular conduction time may also be increased when PRESESE is taken concomitantly with Class-III antidysrhythmic medicines (e.g. amiodarone). The half-life of PRESESE can be slightly shortened by the simultaneous administration of rifampicin. An increase in the dose is generally unnecessary.
• Calcium antagonists, such as verapamil, and to a lesser degree diltiazem, have a negative influence on contractility, atrio-ventricular conduction and blood pressure (see section 4.4). In patients on PRESESE, the I.V. administration of verapamil may cause profound atrioventricular block and hypotension. The use of PRESESE in combination with calcium antagonists is therefore not recommended.
• Clonidine and other centrally acting antihypertensives medicines such as methyldopa, moxonodine and rilmenidine may further decrease heart rate, cardiac output and vasodilation if taken together with PRESESE. Beta-blockers, such as PRESESE may exacerbate the "rebound hypertension" which can occur in case of abrupt withdrawal of centrally acting antihypertensive medicines (e.g. Clonidine). If the two medicines are co-administered, the β-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by β-blocker therapy, the introduction of β-blockers should be delayed for several days after clonidine administration has stopped.
• Mono amine oxidase inhibitors (except MAO-B inhibitors) enhance the hypotensive effect of β-blockers as well as the risk of hypertensive crisis.
• The pharmacokinetics of bisoprolol is not significantly influenced by cimetidine.
• The following combinations should be used with caution together with bisoprolol:
  • Class-I antidysrhythmic medicines (e.g. disopyramide, quinidine), due to a potentiated effect on the atrial conduction time and an increased negative inotropic effect.
  • Class-III antidysrhythmic medicines (e.g. amiodarone), where the effect an atrial conduction time may be potentiated.
• Parasympathomimetic medicines (including tacrine), where atrio-ventricular conduction time and risk of bradycardia may be increased.
• Other β-blockers, including eye drops, have additive effects.
• Insulin and oral antidiabetic medicines, where it can lead to an intensification of the blood sugar lowering effect. Blockade of β-adrenoceptors may mask symptoms of hypoglycaemia.
• Anaesthetic medicines which can lead to attenuation of reflex tachycardia and increase the risk of hypotension. Continuation of β-blockade reduces the risk of dysrhythmia during induction and intubation. The anaesthetist should be informed when the patient is receiving PRESESE.
• Prostaglandin synthetase inhibiting medicines, where the hypotensive effect is decreased.
• Ergotamine derivatives which can lead to an exacerbation of peripheral circulatory disturbances.
• Combinations of sympathomimetic medicines with PRESESE may reduce the effect of both medicines. Higher doses of epinephrine (adrenaline) may be necessary for treatment of allergic reactions.
• PRESESE in combination with tricyclic antidepressants, barbiturates, phenothiazines, as well as other antihypertensive medicines, can lead to an increased blood pressure lowering effect.
• The combination of PRESESE with mefloquine should be considered, as there is an increased risk of bradycardia.

Pregnancy

The use of PRESESE during pregnancy is not recommended (see section 4.3).

PRESESE has pharmacological effects that may cause harmful effects on pregnancy and/or the foetus/newborn. PRESESE reduce placental perfusion, which has been associated with growth retardation, intrauterine death, abortion or early labour.

Administration of PRESESE to pregnant mothers shortly before birth or during labour may result in hypotonia, collapse or hypoglycaemia in the newborn. (See section 4.3).

Breastfeeding

It is not known whether PRESESE passes into breast milk. Therefore, breastfeeding is not recommended during treatment with PRESESE.

Fertility

No effect on fertility was observed in male or female rats treated with bisoprolol at oral doses up to 150 mg/kg/day.

PRESESE may cause drowsiness and dizziness. Do not drive or use any tools or machines until you know how the tablets affect you.

a) Summary of the safety profile

Adverse reactions are more common in patients with renal decompensation.

b) Tabulated list of adverse reactions

• Frequency unknown - cannot be estimated from the available data.

^* This symptom especially occurs at the beginning of therapy. It is generally mild and often disappears within 1–2 weeks.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

Not applicable.