Ventolin^TM Respirator Solution.

Aqueous, colourless to light yellow solution, pH 3.5, providing 5mg/ml of salbutamol (as Salbutamol Sulphate BP).

Solution for nebulisation.

Ventolin Respirator Solution is indicated for use in the routine management of chronic bronchospasm unresponsive to conventional therapy, and in the treatment of acute severe asthma.

Ventolin Respirator Solution is for inhalation use only, to be breathed in through the mouth, under the direction of a physician, using a suitable nebuliser. The solution should not be injected or swallowed. Ventolin Respirator Solution may be administered intermittently or continuously. Salbutamol has a duration of action of 4 to 6 hours in most patients.

Intermittent administration

Adults: Ventolin Respirator solution 0.5ml (2.5mg of salbutamol) should be diluted to a final volume of 2ml with sterile normal saline. This may be increased to 1ml (5mg of salbutamol) diluted to a final volume of 2.5ml. The resulting solution is inhaled from a suitably driven nebuliser until aerosol generation ceases. Using a correctly matched nebuliser and driving source this should take about ten minutes.

Ventolin Respirator Solution may be used undiluted for intermittent administration. For this, 2ml of Ventolin Respirator Solution (10mg of salbutamol) is placed in the nebuliser and the patient allowed to inhale the nebulised solution until bronchodilatation is achieved. This usually takes 3 - 5 minutes. Some adult patients may require higher doses of salbutamol up to 10mg, in which case nebulisation of the undiluted solution may continue until aerosol generation ceases.

Children: The same mode of administration for intermittent administration is also applicable to children. The minimum starting dosage for children under the age of twelve years is 0.5ml (2.5mg of salbutamol) diluted to 2 to 2.5ml with sterile normal saline. Some children may, however, require higher doses of salbutamol up to 5mg. Intermittent treatment may be repeated up to four times daily.

Continuous administration

Ventolin Respirator Solution is diluted with sterile normal saline to contain 50-100 micrograms of salbutamol per ml, (1-2ml solution made up to 100ml with diluent). The diluted solution is administered as an aerosol by a suitably driven nebuliser. The usual rate of administration is 1-2mg per hour.

In infants under 18 months the clinical efficacy of nebulised salbutamol is uncertain. As transient hypoxaemia may occur supplemental oxygen therapy should be considered.

Hypersensitivity.

Threatened abortion.

Ventolin Respirator Solution must only be used by inhalation, to be breathed in through the mouth, and must not be injected or swallowed.

Bronchodilators should not be the only or main treatment in patients with severe or unstable asthma. Severe asthma requires regular medical assessment, including lung-function testing, as patients are at risk of severe attacks and even death. Physicians should consider using the maximum recommended dose of inhaled corticosteroid and/or oral corticosteroid therapy in these patients.

Patients receiving treatment at home should be warned to seek medical advice if treatment with Ventolin Respirator Solution becomes less effective. As there may be adverse effects associated with excessive dosing the dosage or frequency of administration should only be increased on medical advice.

Patients being treated with Ventolin Respirator Solution may also be receiving other dosage forms of short-acting inhaled bronchodilators to relieve symptoms.

Increasing use of bronchodilators, in particular short-acting inhaled β2-agonists, to relieve symptoms, indicates deterioration of asthma control. The patient should be instructed to seek medical advice if short-acting relief bronchodilator treatment becomes less effective, or more inhalations than usual are required. In this situation the patient should be assessed and consideration given to the need for increased anti-inflammatory therapy (e.g. higher doses of inhaled corticosteroid or a course of oral corticosteroid).

Severe exacerbations of asthma must be treated in the normal way.

Cardiovascular effects may be seen with sympathomimetic drugs, including salbutamol. There is some evidence from post-marketing data and published literature of rare occurrences of myocardial ischaemia associated with salbutamol. Patients with underlying severe heart disease (e.g. ischaemic heart disease, arrhythmia or severe heart failure) who are receiving salbutamol 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.

Ventolin Respirator Solution should be used with care in patients known to have received large doses of other sympathomimetic drugs.

Potentially serious hypokalaemia may result from β₂-agonist therapy, mainly from parenteral and nebulised administration. Particular caution is advised in acute severe asthma as this effect may be potentiated by hypoxia and by concomitant treatment with xanthine derivatives, steroids and diuretics. Serum potassium levels should be monitored in such situations.

In common with other β-adrenoceptor agonists, salbutamol can induce reversible metabolic changes such as increased blood glucose levels. Diabetic patients may be unable to compensate for the increase in blood glucose and the development of ketoacidosis has been reported. Concurrent administration of corticosteroids can exaggerate this effect.

Lactic acidosis has been reported in association with high therapeutic doses of intravenous and nebulised short-acting beta-agonist therapy, mainly in patients being treated for an acute asthma exacerbation (see Section 4.8). Increase in lactate levels may lead to dyspnoea and compensatory hyperventilation, which could be misinterpreted as a sign of asthma treatment failure and lead to inappropriate intensification of short-acting beta-agonist treatment. It is therefore recommended that patients are monitored for the development of elevated serum lactate and consequent metabolic acidosis in this setting.

A small number of cases of acute angle-closure glaucoma have been reported in patients treated with a combination of nebulised salbutamol and ipratropium bromide. A combination of nebulised salbutamol with nebulised anticholinergics should therefore be used cautiously. Patients should receive adequate instruction in correct administration and be warned not to let the solution or mist enter the eye.

Salbutamol should be administered cautiously to patients suffering from thyrotoxicosis.

Should not normally be prescribed with non-selective β-blocking drugs such as propranolol.

Administration of drugs during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus. As with the majority of drugs, there is little published evidence of the safety of salbutamol in the early stages of human pregnancy, but in animal studies there was evidence of some harmful effects on the foetus at very high dose levels.

As salbutamol is probably secreted in breast milk, its use in nursing mothers requires careful consideration. It is not known whether salbutamol has a harmful effect on the neonate, and so its use should be restricted to situations where it is felt that the expected benefit to the mother is likely to outweigh any potential risk to the neonate.

None reported.

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 (1/1000 and <1/100), rare (1/10,000 and <1/1000) and very rare (<1/10,000). Very common and common events were generally determined from clinical trial data. Rare, very rare and unknown events were generally determined from spontaneous data.

Immune system disorders

Very rare: Hypersensitivity reactions including angioedema, urticaria, bronchospasm, hypotension and collapse

Metabolism and nutrition disorders

Rare: Hypokalaemia.

Potentially serious hypokalaemia may result from beta₂ agonist therapy.

Unknown: Lactic acidosis (see section 4.4)

Nervous system disorders

Common: Tremor, headache.

Very rare: Hyperactivity.

Cardiac disorders

Common: Tachycardia.

Uncommon: Palpitations

Very rare: Cardiac arrhythmias including atrial fibrillation, supraventricular tachycardia and extrasystoles

Unknown: Myocardial ischaemia* (see section 4.4)

Vascular disorders

Rare: Peripheral vasodilatation.

Respiratory, thoracic and mediastinal disorders

Very rare: Paradoxical bronchospasm.

As with other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with an alternative presentation or a different fast-acting inhaled bronchodilator. Ventolin Respirator Solution should be discontinued immediately, the patient assessed, and, if necessary, alternative therapy instituted.

Gastrointestinal disorders

Uncommon: Mouth and throat irritation.

Musculoskeletal and connective tissue disorders

Uncommon: Muscle cramps.

* reported spontaneously in post-marketing data therefore frequency regarded as unknown

The most common signs and symptoms of overdose with salbutamol are transient beta agonist pharmacologically mediated events, including tachycardia, tremor, hyperactivity and metabolic effects including hypokalaemia and lactic acidosis (see sections 4.4 and 4.8).

Hypokalaemia may occur following overdose with salbutamol. Serum potassium levels should be monitored.

Consideration should be given to discontinuation of treatment and appropriate symptomatic therapy such as cardioselective beta-blocking agents in patients presenting with cardiac symptoms (e.g. tachycardia, palpitations). Beta-blocking drugs should be used with caution in patients with a history of bronchospasm.

Salbutamol is a selective β2-agonist providing short-acting (4-6 hour) bronchodilatation with a fast onset (within 5 minutes) in reversible airways obstruction. At therapeutic doses it acts on the β₂-adrenoceptors of bronchial muscle. With its fast onset of action, it is particularly suitable for the management and prevention of attack in asthma.

Salbutamol administered intravenously has a half-life of 4 to 6 hours and is cleared partly renally and partly by metabolism to the inactive 4'-0-sulphate (phenolic sulphate) which is also excreted primarily in the urine. The faeces are a minor route of excretion. Most of a dose of salbutamol given intravenously, orally or by inhalation is excreted within 72 hours. Salbutamol is bound to plasma proteins to the extent of 10%.

After administration by the inhaled route between 10 and 20% of the dose reaches the lower airways. The remainder is retained in the delivery system or is deposited in the oropharynx from where it is swallowed. The fraction deposited in the airways is absorbed into the pulmonary tissues and circulation, but is not metabolised by the lung. On reaching the systemic circulation it becomes accessible to hepatic metabolism and is excreted, primarily in the urine, as unchanged drug and as the phenolic sulphate.

The swallowed portion of an inhaled dose is absorbed from the gastrointestinal tract and undergoes considerable first-pass metabolism to the phenolic sulphate. Both unchanged drug and conjugate are excreted primarily in the urine.

No additional preclinical safety data are included here.

Preservative: Benzalkonium chloride. Sulphuric acid if required to adjust to pH 3.5.

Purified water.

None known.

Unopened: 3 years. Following opening for the first time: 28 days.

Store below 25^oC. Protect from light. Discard any contents remaining one month after opening the bottle.

Screw-capped 10ml amber glass bottle.

Screw-capped 20ml amber glass bottle.

Inhalation use only, using a suitable nebuliser.

The nebulised solution may be inhaled through a face mask, “T” piece or via an endotracheal tube. Intermittent positive pressure ventilation (IPPV) may be used, but is rarely necessary. When there is a risk of anoxia through hypoventilation, oxygen should be added to the inspired air.

As many nebulisers operate on a continuous flow basis, it is likely that nebulised drug will be released into the local environment. Ventolin Respirator Solution should therefore be administered in a well ventilated room, particularly in hospitals when several patients may be using nebulisers at the same time.

Glaxo Wellcome UK Ltd

trading as Allen & Hanburys

Stockley Park West

Uxbridge

Middlesex UB11 1BT.

PL 10949/0244

06 July 2000

02 July 2009