Each tablet contains 10 mg of Bambuterol hydrochloride.
Excipients/ Inactive Ingredients: One tablet contains: Lactose monohydrate, maize starch, polyvidone, microcrystalline cellulose, magnesium stearate.
Pharmacotherapeutic group: selective β2-agonists, bambuterol. ATC code: R03C C12.
Pharmacology: Pharmacodynamics: Bambuterol hydrochloride (BAMBEC) contains bambuterol, a prodrug of the adrenergic beta-receptor agonist terbutaline, which predominantly stimulates β2-receptors, thus producing relaxation of bronchial smooth muscle, inhibition of the release of endogenous spasmogens, inhibition of oedema caused by endogenous mediators and increased mucociliary clearance.
Pharmacokinetics: About 20% of an oral dose of bambuterol is absorbed. The absorption is not influenced by concomitant intake of food. After absorption, bambuterol is slowly metabolized via hydrolysis (plasma cholinesterase) and oxidation to active terbutaline. About 1/3 of the absorbed dose of bambuterol is metabolized in the intestinal wall and in the liver, mainly to intermediary metabolites.
Of the administered dose of bambuterol, about 10% is converted to terbutaline in adults. Children have a reduced clearance of terbutaline, but they also generate less terbutaline than adults. Therefore children aged 6-12 years should be given adult doses, whereas smaller children (2-5 years) usually need less.
Maximum plasma concentration of the active metabolite terbutaline is achieved within 2-6 hours. The effect-duration is at least 24 hours. Steady-state is reached after 4-5 days of treatment. The plasma half-life of bambuterol after oral administration is about 13 h. The plasma half-life of the active generated metabolite terbutaline is about 21 h.
Bambuterol and its metabolites, including terbutaline, are mainly excreted via the kidneys.
Toxicology: Preclinical safety data: The acute toxicity of bambuterol has been evaluated in studies in mice and rats and is rated as moderate. Repeated dose toxicity studies (1-12 months) in dogs revealed hyperemia, tachycardia and myocardial lesions, observations consistent with the known effects of beta-agonists.
In a 24-month carcinogenicity study in rats, a slightly increased incidence of thyroid follicular adenomas was noted at a dose of bambuterol that was more than 500 times the daily dose in humans. At doses about 150 times the clinical dose no such effect was found. The mechanism of development of thyroid adenomas in rats is considered to be a result of increased secretion of thyroid-stimulating hormone, induced by increased clearance of thyroxine. Such effects have previously been reported for a number of currently marketed drugs.
Bronchial asthma. Chronic bronchitis, emphysema and other lung diseases, where bronchospasm is a complicating factor.
Bambuterol hydrochloride (BAMBEC) should be used as maintenance therapy in asthma and other pulmonary diseases where bronchospasm is a complicating factor. When used as maintenance therapy the patient should also receive optimal anti-inflammatory therapy, e.g. inhaled corticosteroids, leukotriene receptor antagonists.
Bambuterol hydrochloride (BAMBEC) is dosed once daily, preferably shortly before bed-time. The dose should be individual.
Adults: The recommended initial dose is 10 mg. The dose may be increased to 20 mg after 1-2 weeks, depending on the clinical effect. In patients who previously have tolerated oral β2-agonists well, the recommended initial dose is 20 mg.
In patients with an impaired renal function (GFR ≤ 50 ml/min) the recommended initial dose is 5 mg, which may be increased to 10 mg after 1-2 weeks, depending on the clinical effect.
Elderly: Dosage as for adults.
Children 2-5 years: The recommended normal dose is 10 mg and, because of differences in kinetics, 5 mg in East Asian children.
Children 6-12 years: The recommended initial dose is 10 mg. The dose may be increased to 20 mg after 1-2 weeks, depending on the clinical effect.
Children > 12 years: Dosage as for adults.
Because of differences in kinetics, doses above 10 mg are not recommended in Asian children.
Overdosing may result in high levels of terbutaline and therefore the same symptoms and signs as recorded after overdosage with Bricanyl: Headache, anxiety, tremor, nausea, tonic muscle cramps, palpitations, tachycardia and cardiac arrhythmias.
A fall in blood pressure sometimes occurs after terbutaline overdosage.
Laboratory findings: hyperglycemia and lactacidosis sometimes occur. High doses of β2-agonists may cause hypokalemia as a result of redistribution of potassium.
Overdosage with Bambuterol hydrochloride (BAMBEC) is likely to cause a considerable inhibition of plasma cholinesterase, that may last for days (see also under Interactions).
Treatment of overdosage: Usually no treatment is required. In severe cases of overdosage, the following measures should be considered: Gastric lavage, activated charcoal. Determine acid-base balance, blood glucose and electrolytes. Monitor heart rate and rhythm and blood pressure. The preferred antidote for overdosage with Bambuterol hydrochloride (BAMBEC) is a cardioselective β-blocking agent, but beta-blocking drugs should be used with caution in patients with a history of bronchospasm. If the β2-mediated reduction in peripheral vascular resistance significantly contributes to the fall in blood pressure, a volume expander should be given.
Hypersensitivity to any of the ingredients or to terbutaline.
As terbutaline is excreted mainly via the kidneys, the dose of Bambuterol hydrochloride (BAMBEC) should be halved in patients with an impaired renal function (GFR ≤50 mL/min).
In patients with liver cirrhosis, and probably in patients with other causes of severely impaired liver function, the daily dose must be individualized, taking into account the possibility that the individual patient could have an impaired ability to metabolize bambuterol to terbutaline. Therefore, from a practical point of view, the direct use of the active metabolite, terbutaline (Bricanyl), is preferable in these patients.
As for all β2-agonists, caution should be observed in patients with thyrotoxicosis.
Cardiovascular effects may be seen with sympathomimetic drugs, including Bambuterol hydrochloride (BAMBEC). There is some evidence from post-marketing 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 hydrochloride (BAMBEC) 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.
Although Bambuterol hydrochloride (BAMBEC) is not indicated for the treatment of premature labour it should be noted that bambuterol is metabolised to terbutaline and that terbutaline should not be used as a tocolytic agent in patients with pre-existing ischaemic heart disease or those patients with significant risk factors for ischaemic heart disease.
Due to the hyperglycemic effects of β2-agonists, additional blood glucose controls are recommended initially in diabetic patients.
Potentially serious hypokalemia may result from β2-agonist therapy. Particular caution is recommended in acute severe asthma as the associated risk may be augmented by hypoxia. The hypokalemic effect may be potentiated by concomitant treatments (see Interactions). It is recommended that serum potassium levels are monitored in such situations.
Patients with persistent asthma who require maintenance therapy with β2-agonists, should also receive optimal anti-inflammatory therapy e.g. inhaled corticosteroids, leukotriene receptor antagonists. These patients must be advised to continue taking their anti-inflammatory therapy after the introduction of Bambuterol hydrochloride (BAMBEC) even when symptoms decrease. Should symptoms persist, or if treatment with β2-agonists needs to be increased, this indicates a worsening of the underlying condition and warrants a reassessment of the therapy.
Effects of ability to drive and use machines: Bambuterol hydrochloride (BAMBEC) does not affect the ability to drive or use machines.
Although no teratogenic effects have been observed in animals after administration of bambuterol, caution is recommended during the first trimester of pregnancy. It is not known whether bambuterol or intermediary metabolites pass over to breast milk. Terbutaline passes over to breast milk but an influence on the child is unlikely with therapeutic doses. Transient hypoglycemia has been reported in newborn preterm infants after maternal β2-agonist treatment.
Oral slow-release β2-agonists for asthma and other pulmonary disease should be used with caution at the end of pregnancy because of the tocolytic effect.
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. (See Table).
Click on icon to see table/diagram/image
Bambuterol prolongs the muscle-relaxing effect of suxamethonium (succinylcholine). This is due to the fact that plasma cholinesterase, which inactivates suxamethonium, is partly inhibited by bambuterol. The inhibition is dose-dependent and fully reversible after cessation of treatment with bambuterol. This interaction should also be considered with other muscle relaxants which are metabolized by plasma cholinesterase.
Beta-receptor blocking agents (including eye-drops), especially those which are non-selective, may partly or totally inhibit the effect of beta-stimulants.
Halogenated anaesthetics: Halothane anaesthesia should be avoided during β2-agonists treatment, since it increases the risk of cardiac arrhythmias. Other halogenated anesthetics should be used cautiously together with β2-agonists.
Potassium depleting agents and hypokalaemia: 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 (see Precautions). Hypokalaemia also predisposes to digoxin toxicity.
Incompatibilities: Not applicable.
Store at a temperature not exceeding 30°C.
R03CC12 - bambuterol ; Belongs to the class of adrenergics for systemic use, selective beta-2-adrenoreceptor agonists. Used in the treatment of obstructive airway diseases.