Allen & Hanburys Ltd

Ventolin 2mg/5ml Oral Solution

Each 5ml of solution contains 2mg salbutamol as salbutamol sulphate.

Excipients: Contains approximately 5.61mg sodium per 5ml dose.

For a full list of excipients, see section 6.1.

Oral solution.

A clear, colourless to pale straw coloured liquid.

Ventolin Oral Solution is indicated for the relief of bronchospasm such as occurs with asthma, bronchitis and emphysema.

Salbutamol has a duration of action of 4 to 6 hours in most patients.

Increasing use of beta-2 agonists may be a sign of worsening asthma. Under these conditions a reassessment of the patient's therapy plan may be required and concomitant glucocorticosteroid therapy should be considered.

As there may be adverse effects associated with excessive dosing, the dosage or frequency of administration should only be increased on medical advice.

Adults:- The usual total daily dose is 12 to 32mg in three or four divided doses.

Children:-

2 - 6 years: The usual total daily dose is 3 to 8mg in three or four divided doses.

6 - 12 years: The usual total daily dose is 6 to 8mg in divided doses.

Over 12 years: The usual total daily dose is 6 to 16mg in divided doses.

Special patient groups:-

In elderly patients or in those known to be unusually sensitive to beta-adrenergic stimulant drugs, it is advisable to initiate treatment with 5ml of oral solution (2 milligram salbutamol) three or four times per day.

Ventolin Oral Solution is contraindicated in patients with a history of hypersensitivity to sympathomimetics or any component of the preparation.

Although intravenous salbutamol 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 presentations should not be used for threatened abortion.

The management of asthma should normally follow a stepwise programme, and patient response should be monitored clinically and by lung function tests.

Bronchodilators should not be the only or main treatment in patients with severe or unstable asthma. Patients with severe asthma have constant symptoms and frequent exacerbations, with limited physical capacity, and PEF values below 60% predicted at baseline with greater than 30% variability, usually not returning entirely to normal after a bronchodilator. These patients will require high dose inhaled (e.g. >1mg/day beclomethasone dipropionate) or oral corticosteroid therapy. With this primary background corticosteroid treatment, Ventolin provides essential rescue medication for a severe asthmatic in treating acute exacerbations. Failure to respond promptly or fully to such rescue medication signals a need for urgent medical advice and treatment.

Increasing use of short-acting inhaled beta-2 agonists to control symptoms indicates deterioration of asthma control. Under these conditions, the patient's therapy plan should be reassessed. Sudden and progressive deterioration in asthma control is potentially life-threatening and consideration should be given to starting or increasing corticosteroid therapy. In patients considered at risk, daily peak flow monitoring may be instituted

Patients should be warned that if either the usual relief is diminished or the usual duration of action reduced, they should not increase the dose or its frequency of administration, but should seek medical advice.

Salbutamol causes peripheral vasodilation which may result in reflex tachycardia and increased cardiac output. Caution should be used in patients with angina, severe tachycardia or thyrotoxicosis.

Potentially serious hypokalaemia may result from beta-2 agonist therapy mainly from parenteral and nebulised administration. Particular caution is advised in acute severe asthma as this effect may be potentiated by concomitant treatment with xanthine derivatives, steroids, diuretics and by hypoxia. It is recommended that serum potassium levels are monitored in such situations.

In common with other beta-adrenoceptor agonists, Ventolin can induce reversible metabolic changes, for example increased blood sugar levels. The diabetic patient may be unable to compensate for this and the development of ketacidosis has been reported. Concurrent administration of corticosteroids can exaggerate this effect.

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

Salbutamol is not contra-indicated in patients under treatment with monoamine oxidase inhibitors (MAOIs), however the effects of salbutamol may be altered by guanethidine, reserpine, methyldopa and tricyclic antidepressants.

Caution should be exercised in its use with anaesthetic agents such as chloroform, cyclopropane, halothane and other halogenated agents.

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.

Salbutamol has been in widespread use for many years in human beings without apparent ill consequence; this indicates its well-established use in the management of premature labour. However, as with the majority of drugs, there is little published evidence of its safety 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.

During worldwide marketing experience, rare cases of various congenital anomalies, including cleft palate and limb defects have been reported in the offspring of patients being treated with salbutamol. Some of the mothers were taking multiple medications during their pregnancies. Because no consistent pattern of defects can be discerned, and baseline rate for congenital anomalies is 2-3%, a relationship with salbutamol use cannot be established.

As salbutamol is probably secreted in breast milk its use in nursing mothers is not recommended unless the expected benefits outweigh any potential risk.

It is not known whether salbutamol in breast milk has a harmful effect on 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) including isolated reports. Very common and common events were generally determined from clinical trial data. Rare and very rare events were generally determined from spontaneous data.

Symptoms and Signs

The most common signs and symptoms of overdose with salbutamol are transient beta agonist pharmacologically mediated events (see Special Warnings and Precautions for Use and Undesirable Effects).

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.

Treatment

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.

Pharmacotherapeutic group: Selective beta-2-adrenoceptor agonist

ATC code:R03A C02

Salbutamol is a selective beta-2 adrenoceptor agonist. At therapeutic doses it acts on the beta-2 adrenoceptors of bronchial muscle, with little or no action on the beta-1 adrenoceptors of the heart. It is 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'-O-sulphate (phenolic sulphate) which is also excreted primarily in the urine. The faeces are a minor route of excretion. The majority 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 oral administration, salbutamol 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. The bioavailability of orally administered salbutamol is about 50%.

In common with other potent selective beta-2 receptor agonists, salbutamol has been shown to be teratogenic in mice when given subcutaneously. In a reproductive study, 9.3% of foetuses were found to have cleft palate, at 2.5mg/kg, 4 times the maximum human oral dose. In rats, treatment at the levels of 0.5, 2.32, 10.75 and 50mg/kg/day orally throughout pregnancy resulted in no significant foetal abnormalities. The only toxic effect was an increase in neonatal mortality at the highest dose level as the result of lack of maternal care. A reproductive study in rabbits revealed cranial malformations in 37% of foetuses at 50mg/kg/day, 78 times the maximum human oral dose.

Sodium citrate

Citric acid monohydrate

Hypromellose

Sodium benzoate (E211)

Saccharin sodium

Orange flavour IFF 17.42.8187

Sodium chloride

Purified water

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

3 years

Diluted solution: 4 weeks. Discard any unused diluted solution.

Do not store above 25°C.

Store in the original container to protect from light.

For storage of the diluted product, see section 6.3 and protect from light.

It is supplied in Type III amber glass bottles with aluminium screw-caps or HDPE child resistant closures, containing 150ml of Oral Solution.

Not all pack sizes may be marketed.

Salbutamol Oral Solution may be diluted by the pharmacist with an equal volume of Purified Water BP (50% v/v). The resulting mixture contains 1mg/5ml salbutamol. The resulting mixture should be stored in a glass bottle, protected from light and used within 4 weeks. Do not store above 25^oC.

A 50% v/v dilution of salbutamol Oral Solution has been shown to be adequately preserved against microbial contamination.

Admixture of salbutamol Oral Solution with other liquid preparation is not recommended.

GlaxoSmithKline (Ireland) Ltd.,

Stonemasons Way,

Rathfarnham,

Dublin 16.

Trading as: Allen & Hanburys

PA 1077/49/12

1^st April 1980/5^th August 2008

October 2009