Ventolin^TM Accuhaler^TM

Ventolin Accuhaler is a plastic inhaler device containing a foil strip with 60 regularly spaced blisters each containing a mixture of 200 micrograms of microfine salbutamol (as sulphate) and larger particle lactose.

Multi-dose dry powder inhalation device.

Ventolin Accuhaler is indicated in adults, adolescents and children aged 4 to 11 years.

Ventolin Accuhaler can be used in the management of asthma, bronchospasm and/or reversible airways obstruction.

Ventolin Accuhaler is particularly suitable for the relief of asthma symptoms. It should be used to relieve symptoms when they occur, and to prevent them in those circumstances recognised by the patient to precipitate an asthma attack (e.g. before exercise or unavoidable allergen exposure).

Ventolin Accuhaler is particularly valuable as relief medication in mild, moderate or severe asthma, provided that reliance on it does not delay the introduction and use of regular inhaled corticosteroid therapy.

Ventolin Accuhaler is for inhalation use only. Ventolin Accuhaler is suitable for many patients including those who cannot use a metered-dose inhaler successfully.

Adults (including the elderly): For the relief of acute bronchospasm, 200 micrograms as a single dose. The maximum daily dose is 200 micrograms four times a day.

To prevent allergen- or exercise-induced symptoms, 200 micrograms should be taken 10-15 minutes before challenge.

Paediatric Population

Relief of acute bronchospasm

Children aged 4 to 11 years 200 micrograms as required.

Children aged 12 years and over: Dose as per adult population.

Prevention of allergen or exercise-induced bronchospasm

Children aged 4 to 11 years 200 micrograms before challenge or exertion.

Children aged 12 years and over: Dose as per adult population.

Chronic therapy

Children aged 4 to 11 years 200 micrograms four times a day.

On-demand use of Ventolin Accuhaler should not exceed four times daily. Reliance on such frequent supplementary use, or a sudden increase in dose, indicates poorly controlled or deteriorating asthma (see section 4.4).

Children aged 12 years and over: Dose as per adult population.

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, inhaled salbutamol preparations are not appropriate for managing premature labour. Salbutamol preparations should not be used for threatened abortion.

Ventolin Accuhaler is contra-indicated in patients with a history of hypersensitivity to any of the components (see section 6.1).

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.

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.

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.

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

Pregnancy: 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.

Lactation: 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) including isolated reports. 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.

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 Accuhaler 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 (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 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-adrenoceptor agonist. At therapeutic doses it acts on the β₂-adrenoceptors of bronchial muscle, with little or no action on the β₁-adrenoceptors of cardiac muscle.

Salbutamol provides short-acting (4-6 hour) bronchodilation with a fast onset (within 5 minutes) in reversible airways obstruction.

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. 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. Almost all 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%.

In common with other potent selective β₂-receptor agonists, salbutamol has been shown to be teratogenic in mice when given subcutaneously. In a reproductive study, 9.3% of fetuses 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 fetal 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 fetuses at 50mg/kg/day, 78 times the maximum human oral dose.

Lactose (which contains milk protein)

None reported.

24 months.

Do not store above 30°C. Keep in the original container

The powder mix of salbutamol (as sulphate) and lactose is filled into a blister strip consisting of a formed base foil with a peelable foil laminate lid. The foil strip is contained within the Accuhaler device.

The powdered medicine is inhaled through the mouth into the lungs.

The Accuhaler device contains the medicine in individual blisters which areopened as the device is manipulated.

For detailed instructions for use refer to the Patient Information Leaflet in every pack.

Glaxo Wellcome UK Ltd,

trading as Allen & Hanburys,

Stockley Park West,

Uxbridge, Middlesex,

UB11 1BT.

10949/0252

December 1995

13 December 2011