INFORMATION FOR HEALTH PROFESSIONALS
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AIROMIR AUTOHALER contains microcrystalline salbutamol sulphate suspended in a norflurane (HFA-134a) propellant in a pressurised aluminium container closed with a metering valve fitted to a plastic breath activated adaptor. Excipients include oleic acid and ethanol. Each actuation delivers salbutamol sulphate equivalent to 100 mcg ex valve of salbutamol base.
Salbutamol is a relatively selective beta-2 adrenoreceptor stimulant. Administration by inhalation results in direct stimulation of beta-2 receptors in bronchial smooth muscle, and as a result bronchodilation. This is thought to be due to stimulation of adenyl cyclase by salbutamol, resulting in increased levels of cyclic-AMP within cells. This action results in reduction of the entry of calcium ions into the cells and consequent inhibition of smooth muscle contraction. High levels of cyclic-AMP in mast cells also inhibit the release of histamine and SRS-A. It is generally considered that the release of histamine and SRS-A, in response to a Type 1 hypersensitivity reaction, is a primary trigger of allergic asthma.
Patients who have difficulty co-ordinating pressing and breathing in at the same time will gain benefit from the use of an Autohaler. The Autohaler separates these two actions and automatically delivers the prescribed dose to the patient. The Autohaler is breath activated and operates at very low inspiratory flow rates which means it can be used by young children and the elderly.
The Autohaler has been shown to provide a consistent and accurate dose with improved deposition in the lungs compared to metered dose inhalers. The Autohaler has been shown to aid patient confidence and dose perception which has implications for patient compliance in clinical practice in gaining optimal asthma control.
Salbutamol has a 15 minute onset of action on the bronchial smooth muscle and a 6 to 8 hour duration of action. Following administration of salbutamol by aerosol, only 10 to 20% of the dose reaches the lungs, the remainder stays in the mouth, stomach or in the actuator. Salbutamol reaching the lungs acts rapidly and directly on bronchial smooth muscle. Initially salbutamol is undetectable in blood, but after 2 to 3 hours low concentrations are seen, presumably due to the portion of the dose which is swallowed and absorbed from the gastrointestinal system.
The major metabolite of salbutamol, recovered from the urine, has been identified as the 4'-o-sulphate ester and is found after aerosol, oral or intravenous administration. Salbutamol is not metabolised in the lung and the pattern of metabolism and excretion suggests that most of the aerosol is swallowed.
Salbutamol is excreted in the urine either as free salbutamol or its metabolite, although a small fraction is excreted in the faeces. Following inhalation of salbutamol 77 to 97% of the dose is recovered in the urine within 48 hours, with 45 to 60% present as the 4'-o-sulphate ester and the rest as unchanged salbutamol.
As about 60% of orally administered salbutamol is metabolised to an inactive form, impairment of liver function may result in accumulation of unchanged salbutamol. In such patients the dosage may need to be reduced. It is not known whether salbutamol is removed by dialysis. Impairment of renal function may also require a dose reduction to prevent exaggerated or prolonged effects.
AIROMIR AUTOHALER is indicated for the treatment of bronchial asthma and for the treatment of reversible airways obstruction associated with bronchitis and emphysema. It is also suitable for routine maintenance therapy in chronic asthma and chronic bronchitis.
AIROMIR AUTOHALER may be used to relieve attacks of acute dyspnoea and may also be taken before exertion to prevent exercise-induced asthma.
Treatment with AIROMIR AUTOHALER should be in addition to maintenance preventive therapy if this is required.
For the relief of acute bronchospasm, for managing intermittent episodes of asthma, for maintenance of therapy or for prophylactic therapy: one or two inhalations as a single dose. The maximum recommended dose is 16 inhalations a day. For prevention of exercise-induced bronchospasm: two inhalations before exertion.
For the relief of acute bronchospasm, management of episodic asthma or before exercise: one inhalation increasing to two if necessary. The maximum recommended dose is 8 inhalations a day.
The dosage is the same as for other adults.
Initial doses should be reduced to prevent exaggerated or prolonged effects. The dose may then be gradually increased if sufficient bronchodilation is not achieved.
AIROMIR AUTOHALER should be used as directed to gain the full benefit from treatment. Patients should be advised to increase the dose only on medical advice and to report any concerns regarding the appearance of adverse effects. Priming of the inhaler is required for first use by actuating the inhaler to ensure delivery of the stated salbutamol dose. This is not required to be repeated during usual use unless the inhaler is stored and not used for a period longer than two weeks. Patients should be informed of the importance of correct inhaler technique. If necessary, correct technique should be demonstrated to patients, particularly first time users and those with poor coordination. To ensure correct use refer patients to the Consumer Medicine Information accompanying each inhaler.
Management of premature labour and threatened abortion.
Hypersensitivity to salbutamol or other sympathomimetics or any of the inactive ingredients in AIROMIR AUTOHALER.
Failure to obtain relief from AIROMIR may be a medical emergency. The patient should be advised to seek medical advice without delay. The patient should be warned against excessive use of bronchodilator aerosols.
Unwanted stimulation of cardiac adrenergic receptors can occur in patients taking beta-2 agonist therapy. Caution is advised when considering salbutamol treatment for patients with hyperthyroidism or diabetes. Potentially serious hypokalaemia has been reported following parenteral and nebulised beta-2 agonist therapy. Caution is therefore advised with inhaled salbutamol, particularly for acute asthma patients taking concomitant treatment with xanthine derivatives, corticosteroids, diuretics and/or digitalis as these medications can further increase the risk of hypokalaemia. Serum potassium levels should be monitored in these patients and in patients with hypoxia.
Caution is advised when salbutamol is administered to patients who are suffering from cardiovascular diseases such as hypertension, coronary artery disease and myocardial insufficiency.
Salbutamol may predispose patients to or aggravate existing cardiac arrhythmias by direct chronotropic effects on the heart or as a result of hypokalaemia. Salbutamol should therefore be used with caution for patients with known arrhythmias and for patients taking digitalis or diuretic medication.
Caution should be exercised in the use of anaesthetic agents which sensitise the myocardium to circulating sympathomimetic amines.
Since approximately 50% of salbutamol is excreted renally, adjustment of the dose will be necessary if renal function is markedly impaired.
Salbutamol is known to cross the placental barrier in humans. Safety for use in pregnancy has not been demonstrated. In animal studies there has been evidence of some harmful effects on the foetus at very high dose levels. Studies of the propellant administered to pregnant and lactating rats and rabbits have not revealed any special hazard.
In common with other potent selective beta-2 agonists, salbutamol has been shown to be teratogenic in mice when given subcutaneously. Salbutamol should therefore not be used in pregnant women, or those likely to become pregnant, unless the expected benefit outweighs any potential risk. Salbutamol has, however, been used clinically in the treatment of premature labour without adverse effects. Salbutamol causes a rise in blood glucose which is usually of no consequence except in the pregnant diabetic.
It is not known whether salbutamol is excreted in breast milk or has a harmful effect on the newborn. It is therefore not recommended for nursing mothers unless the expected benefits outweigh any potential risk.
Safety studies with this product showed few adverse effects. These occurred at high doses and were consistent with the known effects of salbutamol when administered by inhalation. Since salbutamol is not entirely specific in its effects, it has some stimulant effects on cardiac sensitivity, on the central nervous system and on carbohydrate and fat metabolism. These only become troublesome with relative overdosage or in particularly susceptible subjects.
Overuse of salbutamol preparations may produce significant tachycardia, arrhythmias and hypotension (See Overdosage).
No reported interactions with food or alcohol.
Adrenergic blocking agents inhibit the bronchodilator action of salbutamol and other sympathomimetic bronchodilators. Such medications should not be used in asthmatic patients as they may increase airway resistance.
The risk of hyperglycaemia or hypokalaemia will be increased if oral corticosteroids are given simultaneously. The risk of hypokalaemia may be enhanced during concomitant xanthine or diuretic therapy.
Salbutamol has additive effects with other sympathomimetics and theophylline. Salbutamol should not be given to patients who have already received large doses of sympathomimetics.
Treatment with bendrofluazide augments the hypokalaemic and cardiac effects of high-dose inhaled salbutamol. The arrhythmogenic potential of this interaction may be important in patients with acute exacerbations of chronic airflow obstruction, who have concomitant hypoxaemia and ischaemic heart disease.
Caution is advised if salbutamol is administered concomitantly with tricyclic anti-depressants, digitalis preparations or monoamine oxidase inhibitors (MAOIs).
High doses of salbutamol prior to or shortly after administration of inhaled anaesthetic agents sensitise the myocardium to the effects of sympathomimetic agents and may increase the risk of severe ventricular arrhythmias.
The symptoms of overdosage are the same as the adverse effects of salbutamol, the most significant being tachycardia and/or muscle tremor.
In severe overdosage the use of cardioselective beta-adrenergic antagonist may be necessary, although these agents are likely to decrease airways compliance in asthmatics. It should be noted that beta-blockers may induce bronchospasm in some sensitive patients. Serum potassium levels should also be monitored in the event of overdose. In the case of oral overdosage, gastric lavage should be performed.
AIROMIR AUTOHALER should be stored below 30°C, avoiding direct sunlight or heat and protected from frost. As the canister is pressurised, no attempt should be made to puncture or dispose of it by burning.
Prescription Medicine
200 doses
AIROMIR AUTOHALER has been specially formulated to provide for the aerosol administration of salbutamol with a CFC-free propellant. This inhaler has a different feel and taste to CFC containing inhalers that patients may be using or have used in the past however the clinical efficacy and safety is equivalent. This formulation has been designed to comply with the Montreal Agreement, that requires the phasing out of CFC based aerosol inhalers with the minimum disruption to the dose regimen of the patient. To this end, the new propellant has undergone extensive toxicity, safety and efficacy trials to ensure that the treatment available to the patient is not compromised, and that the dosage of active medication delivered is equivalent to that from other salbutamol aerosol inhalers.
AIROMIR AUTOHALER contains norflurane propellant. In animal studies, norflurane has been shown to have no significant pharmacological effects other than at very high exposure concentrations, where narcosis and a relatively weak cardiac sensitising effect were found. The potency of cardiac sensitisation is less than that of CFC-11 (trichlorofluoromethane). There are no reasons to consider norflurane as a potential mutagen, clastogen or carcinogen judged from in vitro and in vivo studies including long-term administration by inhalation in rodents.
The AIROMIR AUTOHALER adaptor should be cleaned every week by removing the mouthpiece cover then wiping the mouthpiece with a clean, dry cloth or tissue.
3M Pharmaceuticals
a division of 3M New Zealand Limited
P O Box 2201 Shortland Street
AUCKLAND
Telephone: (09) 444 5289
Facsimile: (09) 444 5770
Hoechst Marion Roussel (NZ) Limited
P O Box 12851 Penrose
AUCKLAND
Telephone: (09) 526 4102
Facsimile: (09) 526 4109
Toll Free: 0800 467 467
29 January 1999
™AIROMIR, AUTOHALER and 3M are registered trademarks.