Bambec Tablets 20 mg

Each tablet contains 20 mg Bambuterol hydrochloride

For excipients, see Section 6.1

Tablet

Management of asthma, bronchospasm and/or reversible airways obstruction.

Bambec is formulated as a tablet and should be taken once daily, shortly before bedtime. The dose should be individualised.

Adults: The recommended starting doses are 10 mg–20 mg. The 10 mg dose may be increased to 20 mg if necessary after 1–2 weeks, depending on the clinical effect.

In patients who have previously tolerated β₂agonists well, the recommended starting dose, as well as maintenance dose, is 20 mg.

Children: Until the clinical documentation has been completed, Bambec should not be used in children.

Elderly: Dose adjustment is not required in the elderly.

Significant hepatic dysfunction: Not recommended because of unpredictable conversion to terbutaline.

Moderate to severely impaired renal function (GFR < 50ml/min): It is recommended that the starting dose of Bambec should be halved in these patients.

Bambec tablets are contraindicated in patients with a history of hypersensitivity to any of their ingredients. Bambec is presently not recommended for children due to limited clinical data in this age group.

As terbutaline is excreted mainly via the kidneys, the dose of Bambec should be halved in patients with moderately to severely impaired renal function (GFR 50 mL/min).

Care should be taken with patients suffering from thyrotoxicosis.

Cardiovascular effects may be seen with sympathomimetic drugs, including 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 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.

Due to the hyperglycaemic effects of β₂stimulants, additional blood glucose measurements are recommended initially when Bambec therapy is commenced in diabetic patients.

Due to the positive inotropic effects of β₂agonists these drugs should not be used in patients with hypertrophic cardiomyopathy.

β₂agonists may be arrhythmogenic and this must be considered in the treatment of the individual patient.

Unpredictable inter-individual variation in the metabolism of bambuterol to terbutaline has been shown in subjects with liver cirrhosis. The use of an alternative β₂agonist is recommended in patients with cirrhosis and other forms of severely impaired liver function.

Potentially serious hypokalaemia may result from β₂agonist therapy mainly from parenteral or nebulised administration. Particular caution is advised in acute severe asthma as this effect may be augmented by hypoxia. The hypokalaemic effect may be potentiated by concomitant treatment with xanthine derivatives, corticosteroids and/or diuretics. It is recommended that serum potassium levels are monitored in such situations.

If a previously effective dosage regimen no longer gives the same symptomatic relief, the patient should urgently seek further medical advice. Consideration should be given to the requirements for additional therapy (including increased dosages of anti-inflammatory medication). Severe exacerbations of asthma should be treated as an emergency in the usual manner.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption should not take this medicine.

Bambuterol may interact with suxamethonium (succinylcholine). A prolongation of the muscle-relaxing effect of suxamethonium of up to 2-fold has been observed in some patients after taking Bambec 20 mg on the evening prior to surgery. The interaction is dose-dependent. It is due to the fact that plasma cholinesterase, which inactivates suxamethonium, is partly, but fully reversibly, inhibited by bambuterol. In extreme situations, the interaction may result in a prolonged apnoea time which may be of clinical importance.

Bambuterol may also interact with other muscle relaxants metabolised by plasma cholinesterase.

Beta-receptor blocking agents including eyedrops, especially non-selective ones, may partly or totally inhibit the effect of beta-stimulants. Therefore, Bambec tablets and non-selective βblockers should not normally be administered concurrently. Bambec should be used with caution in patients receiving other sympathomimetics.

Hypokalemia may result from β₂agonist therapy and may be potentiated by concomitant treatment with xanthine derivatives, corticosteroids and diuretics (see Section 4.4, Warnings and Precautions).

Unless there are compelling reasons, avoid in pregnancy, lactation and women of child-bearing potential who are not taking adequate contraceptive precautions. Although no teratogenic effects have been observed in animals after administration of bambuterol, there is no experience of use in human pregnancy. Terbutaline, the active metabolite of bambuterol, has been in widespread clinical use for many years and may be considered in such patients. Terbutaline should be used with caution in the first trimester of pregnancy. Maternal β₂agonist treatment may result in transient hypoglycaemia in pre-term newborn infants.

It is not known whether bambuterol or intermediary metabolites pass into breast milk. Terbutaline does pass into breast milk, but an effect on the infant is unlikely at therapeutic doses.

None stated.

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 < 1/1000), very rare ( <1/10,000 ) and unknown (cannot be estimated from available data).

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

Overdosing may result in high levels of terbutaline.

Symptoms

The signs and symptoms described here have been recorded after terbutaline overdose.

Possible signs and symptoms: Headache, anxiety, tremor, nausea, cramps, palpitations, tachycardia, cardiac arrhythmias. A fall in blood pressure sometimes occurs.

Laboratory findings: Hypokalaemia, hyperglycaemia and lactic acidosis sometimes occur.

Overdose of Bambec is also likely to cause a prolonged inhibition of plasma cholinesterase.

Management

Mild and moderate cases: Reduce the dose.

Severe cases: Administration of activated charcoal if ingestion is recent. Determination of acid-base balance, blood sugar and electrolytes. Monitoring of heart rate and rhythm and blood pressure.

Metabolic changes should be corrected. A cardioselective βblocker (e.g. metoprolol) is recommended for the treatment of haemodynamically significant cardiac arrhythmias. The βblocker should be used with care because of the possibility of inducing bronchoconstriction. Serum potassium levels should be monitored. If the β₂mediated vasodilation contributes significantly to the fall in blood pressure, a volume expander should be given.

Pharmacotherapeutic group: selective β₂agonists, bambuterol, ATC code: R03C C12.

Bambuterol is an active precursor of the selective β₂adrenergic agonist terbutaline. Bambuterol is the bis-dimethylcarbamate of terbutaline, and is present in the formulation as a 1:1 racemate.

Pharmacodynamic studies have shown that after oral administration of bambuterol to guinea pigs, a sustained protective effect was achieved against histamine-induced bronchoconstriction. At equipotent doses, the duration of the relaxing activity was more prolonged than after plain terbutaline. Bambuterol, or the monocarbamate ester, did not exert any smooth muscle relaxing properties. The bronchoprotective effects seen after oral administration of bambuterol are related to the generation of terbutaline, as were the secondary effects (effects on other organs).

Pharmacodynamic studies have been conducted in asthmatics and healthy volunteers. The effects observed were bronchodilation, tremor and increases in heart rate. The metabolic effects included a small increase in blood glucose, while the effect on serum potassium was negligible. In short-term studies on lipoprotein metabolism, an increase in HDL cholesterol, has been observed. In conclusion, all pharmacodynamic effects observed can be ascribed to the active metabolite terbutaline.

On average, 17.5% of an oral dose is absorbed. Approximately 70–90% of the absorption occurs in the first 24 hours.

Bambuterol is metabolised in the liver and terbutaline is formed by both hydrolysis and oxidation. After absorption from the gut, about 2/3 of terbutaline is first-pass metabolised, bambuterol escapes this first-pass metabolism. Of the absorbed amount, about 65% reaches the circulation. Bambuterol therefore has a bioavailability of about 10%.

Protein binding of bambuterol is low, 40–50% at therapeutic concentrations.

The terminal half-life of bambuterol after an oral dose is 9–17 hours.

Studies on the effects on plasma cholinesterase showed that bambuterol inhibited activity, but that this was reversible.

All categories of subjects studied were able to form terbutaline in a predictive way except for liver cirrhotics.

Bambuterol has not revealed any adverse effects which pose a risk to man at therapeutic dosages in the toxicity studies.

Bambuterol is given as a racemate: (-)-bambuterol is responsible for the pharmacodynamic effects via generation of (-)-terbutaline. (+)-bambuterol generates the pharmacodynamic inactive (+)-terbutaline. Both (+) and (-)-bambuterol are equally active as plasma cholinesterase inhibitors. This inhibition is reversible.

The toxicity studies showed that bambuterol has β₂stimulatory effects, expressed as cardiotoxicity in dogs, and at high doses, observed in the acute toxicity studies, cholinergic effects.

There is no evidence from the preclinical safety data to indicate that bambuterol cannot be used in man for the intended indications with sufficient safety.

Lactose monohydrate; maize starch; povidone; microcrystalline cellulose; magnesium stearate; water, purified.

Not applicable.

3 years.

Do not store above 30°C.

Amber glass bottle with LD-polyethene cap: 7, 14, 28, 30, 56 or 100 tablets.

HDPE container with LD-polyethene cap: 7, 14, 28, 30, 56 or 100 tablets.

HDPE container with polypropylene cap: 7, 14, 28, 30, 56 or 100 tablets.

PVC blisters: 7, 14, 28, 30, 56 or 100 tablets.

None.

AstraZeneca UK Ltd.,

600 Capability Green,

Luton, LU1 3LU, UK.

PL 17901/0104

21^st May 2002

26^th June 2009