INFORMATION FOR HEALTH PROFESSIONALS
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RESPOLIN AUTOHALER is a breath activated metered dose inhaler containing an homogenous aerosol suspension of micronised salbutamol sulphate in fluorocarbon propellants. The suspension is contained within a pressurised 10 ml aluminium canister closed with a metering valve and fitted with a plastic oral adaptor. Each actuation delivers salbutamol sulphate equivalent to salbutamol (as the free base) 100 mcg.
Salbutamol is a relatively selective beta-2-adrenoreceptor agonist. Administration by inhalation results in direct stimulation of beta-2 receptors in bronchial smooth muscle and hence bronchodilation. This is thought to be due to stimulation of adenyl cyclase by salbultamol, resulting in increased levels of cyclic AMP within cells. These are thought to inhibit the entry of calcium ions into the cells, thus inhibiting smooth muscle contraction. High levels of cyclic AMP in mast cells also inhibit the release of histamine and SRS-A.
Data on salbutamol pharmocokinetics is limited and can be regarded only as qualitative, but not quantitative. The following relates to aerosol administration of RESPOLIN AUTOHALER. Following administration of salbutamol by aerosol, only 10 to 20% of the dose reaches the lungs, the remainder stays in the mouth, stomach or on the apparatus. 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, due presumably to the portion of the dose which is swallowed and absorbed by the gut.
The major metabolite of salbutamol, recovered from the urine, has been identified as the 4',o-sulphate ester and is found in man after aerosol, oral or intraveneous 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 after 48 hours, 45 to 60% as the 4',o-sulphate ester and the rest as unchanged salbutamol.
The plasma half-life of salbutamol following aerosol or oral administration is between 2.7 to 5 hours.
As about 60% of orally administered salbutamol (this includes not only tablet and syrup preparations but also swallowed aerosol) 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 or not salbutamol is removed by dialysis.
About 60 to 70% of salbutamol administered by inhalation or intravenous injection is excreted in the urine unchanged. Impairment of renal function may therefore require a reduction in dosage to prevent exaggerated or prolonged effects.
RESPOLIN 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, because of its prolonged action.
RESPOLIN AUTOHALER may be used to relieve attacks of acute dyspnoea and may also be taken before exertion to prevent exercise-induced asthma.
For the relief of acute bronchospasm and for managing intermittent episodes of asthma: one or two inhalations as a single dose.
For chronic maintenance therapy: two inhalations, three or four times daily.
For prevention of exercise-induced bronchospasm: two inhalations before exertion, in addition to maintenance therapy if required.
For the relief of acute bronchospasm, management of episodic asthma or before exercise: one inhalation.
For routine maintenance: one inhalation three or four times a day, increasing if necessary, to two inhalations three or four times daily.
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.
Failure to obtain relief from RESPOLIN AUTOHALER 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 aerosols of sympathomimetic agents.
Caution is advised when salbutamol is administered to patients who are suffering from cardiovascular diseases such as hypertension, coronary artery disease, myocardial insufficiency.
Salbutamol may predispose to or aggravate existing cardiac arrhythmias by direct chronotropic effects on the heart or by producing hypokalaemia. Salbutamol should therefore be used with caution in patients with known arrhythmias and in patients taking digitalis or diuretic medication.
Caution should be exercised in the use of anaesthetic agents that sensitise the myocardium to circulating sympathomimetic amines.
Salbutamol is known to cross the placental barrier in humans. Safety for use in pregnancy has not been demonstrated, therefore salbutamol should not be used in pregnant women, or those likely to become pregnant, unless the expected benefit outweighs any potential risk. However, salbutamol has been used clinically in the treatment of premature labour without adverse effects.
It is not known whether salbutamol is excreted in breast milk nor whether it has a harmful effect on the newborn. Therefore it is not recommended for nursing mothers unless the expected benefits outweigh any potential risk.
As with many other pressurised aerosol formulations, salbutamol metered aerosols contain fluorocarbon propellants. In large doses these propellants can produce cardiac arrhythmia in animals as well as sensitise their hearts to adrenaline induced arrhythmia. Data in humans is meagre. Excessive inhalation of the aerosol should be avoided as this carries a potential hazard both from the propellant and as well from overdosage of salbutamol contained in the formulation.
The incidence and severity of particular side effects depends on the dosage and route of administration.
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. However, such medications should not be used in asthmatic patients as they may increase airway resistance.
Other adrenergic stimulants or sympathomimetic amines such as ephedrine should not be given concomitantly. Salbutamol should not be given to patients who have already received large doses of sympathomimetics.
All of the stated adverse reactions may occur. Significant tachycardia, muscle tremor and superficial vasodilation are common. Arrhythmias, hypotension and sudden death have been reported in cases of overuse of pressurised aerosols. but some of these effects may be due to the aerosol propellant, rather than to salbutamol.
Gastric lavage should be performed in cases of oral overdosage. The specific antidote for salbutamol overdosage is a beta-2 selective adrenoceptor antagonist given by intravenous injection. In general beta-blockers should be used cautiously in patients with a history of bronchospasm.
Store below 30°C, avoiding direct sunlight or heat.
Prescription Medicine
400 doses
RESPOLIN AUTOHALER has been specially formulated using salbutamol sulphate to significantly reduce the fluorocarbon propellant delivered with each dose to 25 microlitres. Patients previously using other salbutamol aerosols will notice a significant decrease in the volume and impact of the aerosol discharge but should be reassured that the dosage of active medication delivered is in fact equivalent.
RESPOLIN AUTOHALER is not contraindicated in patients under treatment with monoamine oxidase inhibitors.
3M Pharmaceuticals
a division of 3M New Zealand Limited
P.O. Box 2201 Shortland Street
AUCKLAND
Telephone: (09) 444 5289
Facsimile: (09) 444 5770
8 September 1997
™RESPOLIN, AUTOHALER and 3M are registered trademarks.