Bambuterol

Owing to the hypokalaemic effect of beta agonists, concurrent administration of serum potassium depleting agents known to exacerbate the risk of hypokalaemia, such as diuretics, methyl xanthines and corticosteroids, should be administered cautiously after careful evaluation of the benefits and risks with special regard to the increased risk of cardiac arrhythmias arising as a result of hypokalaemia. Hypokalaemia also predisposes to digoxin toxicity.

It is recommended that the starting dose of bambuterol should be halved in these patients.

Beta-receptor blocking agents (including eye-drops), especially those which are non-selective, may partly or totally inhibit the effect of beta-stimulants. Therefore, bambuterol and non-selective β-blockers should not normally be administered concurrently.

Halothane anaesthesia should be avoided during β₂-agonists treatment, since it increases the risk of cardiac arrhythmias. Other halogenated anaesthetics should be used cautiously together with β₂-agonists.

Bambuterol prolongs the muscle-relaxing effect of suxamethonium (succinylcholine). A prolongation of the musclerelaxing effect of suxamethonium of up to 2-fold has been observed in some patients after taking bambuterol 20 mg on the evening prior to surgery. The inhibition is dose-dependent and fully reversible after cessation of treatment with bambuterol. This is due to the fact that plasma cholinesterase, which inactivates suxamethonium, is partly inhibited by bambuterol. Studies on the effects on plasma cholinesterase showed that bambuterol inhibited activity, but that this was reversible. However in extreme situations, the interaction may result in a prolonged apnoea time which may be of clinical importance. This interaction should also be considered with other muscle relaxants, which are metabolised by plasma cholinesterase.

In patients with liver cirrhosis, and probably in patients with other causes of severely impaired liver function, the daily dose must be individualised, taking into account the possibility that the individual patient could have an impaired ability to metabolise bambuterol to terbutaline. Therefore, from a practical point of view, the direct use of the active metabolite, terbutaline, is preferable in these patients.

Due to the positive inotropic effects of β₂-agonists these drugs should not be used in patients with hypertrophic cardiomyopathy.

Potentially serious hypokalaemia may result from β₂-agonist therapy. Particular caution is recommended in acute severe asthma as the associated risk may be augmented by hypoxia. The hypokalaemic effect may be potentiated by concomitant treatments. It is recommended that serum potassium levels are monitored in such situations.

Precaution should be applied when treating patients predisposed to angle closure glaucoma.

Cardiovascular effects may be seen with sympathomimetic drugs, including bambuterol. There is some evidence from postmarketing data and published literature of rare occurrences of myocardial ischaemia associated with beta agonists.

Patients with underlying severe heart disease (e.g. ischaemic heart disease, arrhythmia or severe heart failure) who are receiving bambuterol should be warned to seek medical advice if they experience chest pain or other symptoms of worsening heart disease. Attention should be paid to assessment of symptoms such as dyspnoea and chest pain, as they may be of either respiratory or cardiac origin.

Due to the hyperglycaemic effects of β₂-agonists, additional blood glucose controls are recommended initially in diabetic patients.

As for all β₂-agonists, caution should be observed in patients with thyrotoxicosis.

Although no teratogenic effects have been observed in animals after administration of bambuterol, caution is recommended during the first trimester of pregnancy.

Beta-agonists for asthma and other pulmonary diseases should be used with caution at the end of pregnancy because of the tocolytic effect.

Transient hypoglycaemia has been reported in newborn preterm infants after maternal β₂-agonist treatment.

It is unknown whether bambuterol or intermediary metabolites are excreted in human breast milk. Terbutaline, the active metabolite of bambuterol, is excreted in breast milk, but at therapeutic doses of terbutaline no effect on breastfed newborns/infants are anticipated. A decision must be made whether to discontinue breast-feeding or to discontinue bambuterol therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Bambuterol has no or negligible influence on the ability to drive and use machines.

Most of the adverse reactions are characteristic of sympathomimetic amines. The intensity of the adverse reactions is dose-dependent. Tolerance to these effects has usually developed within 1-2 weeks.

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000) and Not known (cannot be estimated from available data).

Immune system disorders

Not known: Hypersensitivity reactions including Angioedema, Urticaria, Exanthema, Bronchospasm, Hypotension and Collapse

Metabolism and nutrition disorders

Not known: Hypokalemia, Hyperglycaemia

Psychiatric disorders

Very Common: Behavioural Disturbances, such as Restlessness

Common: Sleep disturbances

Uncommon: Behavioural Disturbances, such as Agitation

Not known: Dizziness, Hyperactivity

Nervous system disorders

Very common: Tremor, Headache

Cardiac disorders

Common: Palpitations

Uncommon: Tachycardia, Cardiac arrhythmias, e.g. Atrial Fibrillation, Supraventricular tachycardia and Extrasystoles

Not known: Myocardial ischemia

Respiratory, thoracic and mediastinal disorders

Unknown: Paradoxical bronchospasm

Gastrointestinal disorders

Not known: Nausea

Musculoskeletal, connective tissue and bone disorders

Common: Muscle cramps