Salbutamol 2mg/Ml Nebuliser Solution
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Salbutamol 2mg/ml Nebuliser Solution
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each nebule contains 5mg / 2.5ml salbutamol (as sulphate).
For full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Nebuliser Solution (for use via a nebuliser).
Plastic ampoule containing 2.5 ml of a clear sterile solution containing 5mg salbutamol (as sulphate) in normal saline.
4. CLINICAL PARTICULARS
4.1. Therapeutic indications
Salbutamol nebuliser solutions are indicated in adults, adolescents and children aged
4 years to 11 years., For babies and children under 4 years of age, see section 4.2.
Salbutamol is a selective p2-agonist providing short-acting (4-6 hour) bronchodilation with a fast onset (within 5 minutes) in reversible airways obstruction.
Salbutamol nebuliser solutions are indicated for use in the routine management of chronic bronchospasm unresponsive to conventional therapy, and in the treatment of acute severe asthma.
4.2. Posology and method of administration
Posology
Adults (including the elderly): 2.5mg to 5mg salbutamol up to four times a day. Up to 40mg per day can be given under strict medical supervision in hospital.
Paediatric Population
Children aged 12 years and over: Dose as per adult population.
Children aged 4 - 11 years: 2.5mg to 5mg up to four times a day.
Other pharmaceutical forms may be more appropriate for administration in children under 4 years old.
Infants under 18 months old: Clinical efficacy of nebulised salbutamol in infants under 18 months is uncertain. As transient hypoxia may occur, supplemental oxygen therapy should be considered.
Salbutamol nebulisers solutions are intended to be used undiluted. However, if prolonged delivery time (more than 10 minutes) is required, the solution may be diluted with sterile normal saline.
Method of administration
Salbutamol nebuliser solutions are 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.
4.3. Contraindications
Hypersensitivity to salbutamol or to any of the excipients listed in section 6.1.
Non-IV formulations of salbutamol must not be used to arrest uncomplicated premature labour or threatened abortion.
4.4. Special warnings and precautions for use
Salbutamol nebuliser solution must only be used by inhalation, to be breathed in through the mouth, and must not be injected or swallowed.
Potentially serious hypokalaemia has been reported in patients taking P-2-agonist therapy. Particular caution is advised in patients with severe asthma as hypokalaemia may be potentiated in hypoxic patients and those treated with xanthine derivatives, steroids, diuretics. In these groups of patients serum potassium levels should be monitored.
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 or even death. Physicians should consider using the maximum recommended dose of inhaled corticosteroid and/or oral corticosteroid therapy in these patients.
Patients being treated with salbutamol nebuliser solution may also be receiving other dosage forms of short-acting inhaled bronchodilators to relieve symptoms. Increasing use of bronchodilators, in particular short-acting p2- agonists to relieve symptoms indicates deterioration of asthma control. The patients 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 patients 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.
Salbutamol should be administered cautiously to patients suffering from thyrotoxicosis.
Salbutamol nebuliser solutions should be used with care in patients known to have received large doses of other sympathomimetic drugs.
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 or chest pain, as they may be of either respiratory or cardiac origin.
In common with other P- 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 eyes.
Patients receiving treatment at home should seek medical advice if treatment with salbutamol nebuliser solutions becomes less effective. The dosage or frequency of administration should only be increased on medical advice.
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.
Salbutamol nebuliser solutions should be discontinued, and if necessary a different fast-acting bronchodilator instituted for on-going use.
4.5. Interactions with other medicinal products and other forms of interaction
Salbutamol and non-selective P-blocking drugs such as propranolol, should not usually be prescribed together.
4.6. Fertility, pregnancy and lactation
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.
Breast-feeding
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.
Fertility
There is no information on the effects of salbutamol on human fertility. There were no adverse effects on fertility in animals (see section 5.3).
4.7 Effects on ability to drive and use machines
None reported.
4.8. Undesirable effects
Adverse reactions are listed 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); 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: Headache, tremor.
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.
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
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9. Overdose
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. Lactic acidosis has been reported in association with high therapeutic doses as well as overdoses of short-acting beta-agonist therapy, therefore monitoring for elevated serum lactate and consequent metabolic acidosis (particularly if there is persistence or worsening of tachypnea despite resolution of other signs of bronchospasm such as wheezing) may be indicated in the setting of overdose.
5. PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic properties
Pharmacotherapeutic group: Andrenergics, inhalants. Selective p2-andrenoreceptor agonists
ATC code: R03A C02
Salbutamol is a selective p2-agonist providing short-acting (4-6 hour) bronchodilation with a fast onset (within 5 minutes) in reversible airways obstruction. At therapeutic doses it acts on p2-adrenoceptors of bronchial muscle. With its fast onset of action, it is particularly suitable for the management and prevention of attack in asthma.
5.2. Pharmacokinetic properties
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-sulfate (phenolic sulfate) 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 between10 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 sulfate.
The swallowed portion of an inhaled dose is absorbed from the gastrointestinal tract and undergoes considerable first-pass metabolism to the phenolic sulfate. Both unchanged drug and conjugate are excreted primarily in the urine.
5.3. Preclinical safety data
In an oral fertility and general reproductive performance study in rats at doses of 2 and 50 mg/kg/day, with the exception of a reduction in number of weanlings surviving to day 21 post partum at 50 mg/kg/day, there were no adverse effects on fertility, embryofetal development, litter size, birth weight or growth rate.
6.1 List of excipients
Sodium chloride Sulphuric acid to adjust pH Water for injection
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years unopened.
3 months after opening the foil over-wrap.
6.4 Special precautions for storage
Store in the original package.
The ampoules should be protected from light after removal from the foil over-wrap.
6.5 Nature and contents of container
Plastic polyethylene ampoules in strips of 5 ampoules, with a protective foil over-wrap. Available in boxes containing 20 ampoules
6.6 Special precautions for disposal
Nebulisers should be used in a well ventilated room as it is usual for some nebulised drug to be released into the local environment.
Dilution: May be diluted with sterile sodium chloride solution, (normal saline) if required.
For instructions on the use of this product refer to the Patient Information Leaflet.
7 MARKETING AUTHORISATION HOLDER
Cipla (EU) Limited
Hillbrow House
Hillbrow Road
Esher
Surrey
KT10 9NW
8 MARKETING AUTHORISATION NUMBER(S)
PL 36390/0036
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
06/06/2011
10 DATE OF REVISION OF THE TEXT
27/01/2016