Bricanyl^® Turbohaler^®, 0.5mg/dose, inhalation powder

Terbutaline Sulphate 0.5mg/dose.

For excipients see Section 6.1.

Inhalation powder.

Breath-actuated metered dose powder inhaler.

Terbutaline is a selective beta₂-adrenergic agonist recommended for the relief and prevention of bronchospasm in bronchial asthma and other bronchopulmonary disorders in which bronchospasm or reversible airways obstruction is a complicating factor.

Adults and Children: One inhalation (0.5mg) as required. Not more than 4 inhalations should be required in any 24-hour period.

The duration of action of a single dose is up to 6 hours.

Elderly: Dosage as for adults.

Instructions for use and cleaning are provided in the Patient Information Leaflet, which can be found in each pack.

Bricanyl preparations are contraindicated in patients with a history of sensitivity to terbutaline sulphate.

Patients should be instructed in proper use and their inhalation technique checked regularly.

With each inhalation a fraction of the delivered dose will be deposited in the oral cavity. To minimize unnecessary systemic exposure to terbutaline, the patients should be advised to, when possible, rinse their mouth after each use.

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.

As for all beta₂-agonists caution should be observed in patients with thyrotoxicosis.

Due to the positive inotropic effect of beta₂-agonists, these drugs should not be used in patients with hypertrophic cardiomyopathy.

Cardiovascular effects may be seen with sympathomimetic drugs, including Bricanyl. 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 Bricanyl 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 beta₂-agonists, additional blood glucose controls are recommended initially in diabetic patients.

Potentially serious hypokalaemia may result from beta₂-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 (see section 4.5, Interactions). It is recommended that serum potassium levels are monitored in such situations.

Beta-blocking agents (including eye drops), especially the non-selective ones such as propranolol, may partially or totally inhibit the effect of beta-stimulants. Therefore, Bricanyl preparations and non-selective beta-blockers should not normally be administered concurrently. Bricanyl should be used with caution in patients receiving other sympathomimetics.

Hypokalaemia may result from beta₂-agonist therapy and may be potentiated by concomitant treatment with xanthine derivatives, corticosteroids and diuretics (see Section 4.4, Special Warnings and Precautions for use).

Although no teratogenic effects have been observed in animals or in patients, Bricanyl should only be administered with caution during the first trimester of pregnancy.

Terbutaline is secreted via breast milk but any effect on the infant is unlikely at therapeutic doses.

None.

The frequency of adverse reactions is low at the recommended dose. Terbutaline given by inhalation is unlikely to produce significant systemic effects when given in recommended doses. Most of the adverse reactions are characteristic of sympathomimetic amines. The majority of these effects have reversed spontaneously within the first 1-2 weeks of treatment.

The frequency of side-effects is low at the recommended doses.

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100 and <1/10), uncommon (>1/1,000 and <1/100), rare (>1/10,000 and <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

# A few patients feel tense; this is also due to the effects on skeletal muscle and not to direct CNS stimulation.

^ Reported spontaneously in post-marketing data and therefore frequency regarded as unknown

* In rare cases, through unspecified mechanisms, paradoxical bronchospasm may occur, with wheezing immediately after inhalation. This should be immediately treated with a rapid-onset bronchodilator. Bricanyl therapy should be discontinued and after assessment, an alternative therapy initiated.

i) Possible symptoms and signs:

Headache, anxiety, tremor, nausea, tonic cramp, palpitations, tachycardia and arrhythmia. A fall in blood pressure sometimes occurs. Laboratory findings: Hypokalaemia, hyperglycaemia and metabolic acidosis sometimes occur.

ii) Treatment:

Mild and moderate cases: Reduce the dose.

Severe cases: Gastric lavage, administration of activated charcoal (where suspected that significant amounts have been swallowed). Determination of acid-base balance, blood sugar and electrolytes, particularly serum potassium levels. Monitoring of heart rate and rhythm and blood pressure. Metabolic changes should be corrected. A cardioselective beta-blocker (e.g. metoprolol) is recommended for the treatment of arrhythmias causing haemodynamic deterioration. The beta-blocker should be used with care because of the possibility of inducing bronchoconstriction: use with caution in patients with a history of bronchospasm. If the beta₂-mediated reduction in peripheral vascular resistance significantly contributes to the fall in blood pressure, a volume expander should be given.

Pharmaco-therapeutic group: selective beta₂-agonist, terbutaline, ATC code: R03A C03.

Terbutaline sulphate is a selective beta₂-adrenoceptor agonist, thus producing relaxation of bronchial smooth muscle, inhibition of the release of endogenous spasmogens, inhibitions of oedema caused by endogenous mediators, increased mucociliary clearance and relaxation of the uterine muscle.

Pharmacokinetic data from terbutaline inhaled from a pressurised aerosol reveal that less than 10% of the dose is absorbed from the airways. The remaining 90% is swallowed but is largely prevented from entering the systemic circulation due to extensive first pass metabolism.

Data suggest that inhaled terbutaline acts topically in the airways.

The major toxic effect of terbutaline, observed in toxicological studies in rats and dogs at exposures in excess of maximum human exposure, is focal myocardial necrosis. This type of cardiotoxicity is a well known pharmacological manifestation seen after the administration of high doses of beta₂-agonists.

In rats, an increase in the incidence of benign uterine leiomyomas has been observed. This effect is looked upon as a class-effect observed in rodents after long term exposure to high doses of beta₂-agonists.

None

None known.

24 months

Do not store above 30°C.

Bricanyl Turbohaler consists of a number of assembled plastic details, the main parts being the dosing mechanism, the drug substance store, the desiccant store and the mouthpiece. The inhaler is protected by an outer tubular cover screwed onto a bottom plate.

Each inhaler contains 100 doses.

None.

AstraZeneca UK Ltd.,

600 Capability Green,

Luton, LU1 3LU, UK.

PL 17901/0117

4^th June 2002 / 12^th May 2007

28^th October 2011