Ventolin^TM Solution for Intravenous Infusion 5mg in 5ml (1mg/ml).

Ventolin Solution for Intravenous Infusion 5mg in 5ml (1mg/ml) is presented as ampoules of 5ml, each containing 5mg salbutamol as Salbutamol Sulphate BP in a sterile isotonic solution.

Clear, colourless or pale straw-coloured solution for intravenous infusion.

Ventolin Solution for Intravenous Infusion should be administered under the direction of a physician. It is indicated for two distinct clinical situations:

a) For the relief of severe bronchospasm.

b) In the management of premature labour; to arrest uncomplicated labour between 24 and 33 weeks of gestation in patients with no medical or obstetric contra-indication to tocolytic therapy. Data suggest that the main effect of tocolytic therapy is a delay in delivery of up to 48 hours. This delay may be used to administer glucocorticoids or to implement other measures known to improve perinatal health.

Ventolin Solution for Intravenous Infusion is used to prepare an infusion solution. It should not be injected undiluted. Ventolin Solution for Intravenous Infusion should not be administered in the same syringe or infusion as any other medication.

1) In severe bronchospasm.

Adults: A suitable solution for infusion providing 10 micrograms salbutamol/ml is prepared by diluting 5ml Ventolin Solution for Intravenous Infusion to 500ml with an infusion solution such as Sodium Chloride and Dextrose Injection BP. Other suitable diluents are Water for Injections BP, Sodium Chloride Injection BP or Dextrose Injection BP.

Infusion rates providing 3 to 20 micrograms salbutamol/minute (0.3 to 2ml/minute of the above infusion solution) are usually adequate. Higher doses have been used with success in patients with respiratory failure. Children: There are insufficient data to recommend a dosage regime for routine use.

2. In the management of premature labour.

The infusion, prepared as described below, should be administered as early as possible after the diagnosis of premature labour, and after evaluation of the patient to eliminate any contra-indications to the use of salbutamol (see section 4.3).

During infusion the maternal pulse rate should be monitored and the infusion rate adjusted to avoid excessive maternal heart rate (above 140 beats/minute).

It is essential that the volume of infusion fluid is kept to a minimum to control the level of hydration and so avoid the risk of maternal pulmonary oedema. Treatment discontinuation should be considered should signs of pulmonary oedema or myocardial ischaemia develop (see section 4.8) A controlled infusion device, preferably a syringe pump, should be used.

Infusion rates providing 10 to 45 micrograms salbutamol/minute are generally adequate to control uterine contractions. A starting rate of 10 micrograms/minute is recommended, increasing the rate at 10-minute intervals until there is evidence of patient response shown by diminution in strength, frequency or duration of contractions. Thereafter, the infusion rate may be increased slowly until contractions cease. Careful attention should be given to cardio-respiratory function and fluid balance monitored. Once uterine contractions have ceased the infusion rate should be maintained at the same level for one hour and then reduced by 50% decrements at six hourly intervals. If labour progresses despite treatment the infusion should be stopped. If contractions have been successfully inhibited by the infusion, treatment may be continued orally with Ventolin Tablets 4mg given three or four times daily.

Dilution: The recommended diluent is 5% Dextrose (see section 4.3 for precautions with diabetic patients).

For use in a syringe pump: Prepare a solution providing 200 micrograms salbutamol/ml by diluting 10ml Ventolin Solution for Intravenous Infusion with 40ml diluent. An infusion rate of 10 to 45 micrograms/minute is equivalent to 0.05 to 0.225ml/minute of this solution.

Other infusion methods: Prepare a solution providing 20 micrograms salbutamol/ml by diluting 10ml Ventolin Solution for Intravenous Infusion with 490ml diluent. An infusion rate of 10 to 45 micrograms/minute is equivalent to 0.5 to 2.25ml/minute of this solution.

Instructions to open the ampoule

Ampoules are equipped with the OPC (One Point Cut) opening system and must be opened using the following instructions:

• hold with one hand the bottom part of the ampoule as indicated in Picture 1

• put the other hand on the top of the ampoule positioning the thumb above the coloured point and press as indicated in Picture 2

Picture 1

Picture 2

Although Ventolin Solution for Intravenous Infusion and occasionally salbutamol tablets, are used in the management of premature labour uncomplicated by conditions such as placenta praevia, ante-partum haemorrhage or toxaemia of pregnancy, salbutamol preparations should not be used for threatened abortion.

Ventolin Solution for Intravenous Infusion is contra-indicated in patients with a history of hypersensitivity to any of the components.

Salbutamol should not be used as a tocolytic agent in patients with pre-existing ischaemic heart disease or those patients with significant risk factors for ischaemic heart disease

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.

The dosage or frequency of administration should only be increased on medical advice.

Patients being treated with Ventolin Solution for Intravenous Infusion may also be receiving 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. The use of Ventolin Solution for Intravenous Infusion in the treatment of severe bronchospasm does not obviate the requirement for corticosteroid therapy as appropriate. When practicable, administration of oxygen concurrently with parenteral Ventolin is recommended, particularly when it is given by intravenous infusion to hypoxic patients. In common with other β-adrenoceptor agonists, salbutamol can induce reversible metabolic changes such as hypokalaemia and 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.

Therefore, diabetic patients and those concurrently receiving corticosteroids should be monitored frequently during intravenous infusion of Ventolin so that remedial steps (e.g. an increase in insulin dosage) can be taken to counter any metabolic change occurring. For these patients it may be preferable to dilute Ventolin Solution for Intravenous Infusion in Sodium Chloride Injection BP rather than in diluents containing dextrose.

Cardiovascular effects may be seen with sympathomimetic drugs, including salbutamol. There is some evidence from post-marketing data and published literature of myocardial ischaemia associated with salbutamol.

Tocolysis

Salbutamol should be used with caution in tocolysis and supervision of cardiorespiratory function, including ECG monitoring, should be considered. Treatment should be discontinued if signs of myocardial ischaemia (such as chest pain or ECG changes) develop. Salbutamol should not be used as a tocolytic agent in patients with significant risk factors for or pre-existing heart disease (see section 4.3).

Respiratory indications

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.

Salbutamol should be administered cautiously to patients suffering from thyrotoxicosis.

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.

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.

As maternal pulmonary oedema and myocardial ischaemia have been reported during or following treatment of premature labour with β₂-agonists, careful attention should be given to fluid balance and cardio-respiratory function, including ECG, should be monitored. If signs of pulmonary oedema or myocardial ischaemia develop, discontinuation of treatment should be considered (see 4.2 and 4.8). In patients being treated for premature labour by intravenous infusion of salbutamol, increases in maternal heart rate of the order of 20 to 50 beats per minute usually accompany the infusion. The maternal pulse rate should be monitored and not normally allowed to exceed a steady rate of 140 beats per minute. Maternal blood pressure may fall slightly during the infusion; the effect being greater on diastolic than on systolic pressure. Falls in diastolic pressure are usually within the range of 10 to 20mmHg. The effect of infusion on fetal heart rate is less marked, but increases of up to 20 beats per minute may occur. In the treatment of premature labour, before Ventolin Solution for Intravenous Infusion is given to any patient with known heart disease, an adequate assessment of the patient's cardiovascular status should be made by a physician experienced in cardiology. In order to minimise the risk of hypotension associated with tocolytic therapy, special care should be taken to avoid caval compression by keeping the patient in the left or right lateral positions throughout the infusion.

Ventolin Solution for Intravenous Infusion should not be administered in the same syringe or infusion as any other medication.

Salbutamol and non-selective β-blocking drugs such as propranolol, should not usually be prescribed together.

Administration of drugs during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the fetus. 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 fetus 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 ß₂-agonist therapy.

Unknown: Lactic acidosis(see section 4.4)

Nervous system disorders

Very common: Tremor.

Common: Headache.

Very rare: Hyperactivity.

Cardiac disorders

Very common: Tachycardia.

Common: Palpitations.

Unknown: Myocardial ischaemia* (see section 4.4)

Rare: Cardiac arrhythmias including atrial fibrillation, supraventricular tachycardia and extrasystoles.

* In the management of pre-term labour with salbutamol solution for infusion.

Vascular disorders

Rare: Peripheral vasodilatation.

Respiratory, thoracic and mediastinal disorders

Uncommon: Pulmonary oedema.

In the management of pre-term labour, Ventolin Solution for Intravenous Infusion has uncommonly been associated with pulmonary oedema. Patients with predisposing factors including multiple pregnancies, fluid overload, maternal infection and pre-eclampsia may have an increased risk of developing pulmonary oedema.

Gastrointestinal disorders

Unknown: Nausea, vomiting.

In the management of premature labour, intravenous infusion of Ventolin has very rarely been associated with nausea and vomiting.

Musculoskeletal and connective tissue disorders

Common: Muscle cramps.

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.

Nausea, vomiting and hyperglycaemia have been reported, predominantly in children and when salbutamol overdose has been taken via the oral route.

Consideration should be given to discontinuation of treatment and appropriate symptomatic therapy such as cardio-selective 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 which acts on the β₂-adrenoceptors of the bronchi and uterus.

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%.

No additional preclinical safety data are included here.

Sodium chloride, sodium hydroxide, sulphuric acid and Water for Injections.

None stated.

36 months.

24 hours after mixing with infusion fluids.

Store below 30°C and keep container in the outer carton.

Clear, neutral glass ampoules, available in boxes of 10 ampoules or 5 ampoules.

Ventolin Solution for Intravenous Infusion must be diluted before use. The recommended diluents are Water for Injections BP, Sodium Chloride Injection BP, Sodium Chloride and Dextrose Injection BP and Dextrose Injection BP (see section 4.2).

All unused admixtures of Ventolin Solution for Intravenous Infusion with infusion fluids should be discarded twenty-four hours after preparation.

Glaxo Wellcome UK Ltd,

trading as Allen & Hanburys,

Stockley Park West,

Uxbridge,

Middlesex,

UB11 1BT.

PL 10949/0087

11 September 2000

31 July 2009

Ventolin™ is a trade mark of the Glaxo Wellcome Group of Companies