Parenteral > General injections > IV:
50 µg per mL in 5 mL ampoule (as sulfate) Respiratory > Inhalation > aerosol:
100 µg per dose (as sulfate) ;
100 µg per dose (as sulfate) metered-dose inhaler Respiratory > Inhalation > solution:
5 mg per mL (as sulfate) for use in nebulizers
Summary of evidence and Expert Committee recommendations
Formulations of salbutamol on the EML were updated, with orally administered formulations removed.
The Committee received a review on the proposed deletion of oral forms of salbutamol. The application was prepared by Dr Shalini Sri Ranganathan.
An expert review was provided by Professor Anita Zaidi. Comments were also provided by Dr Shanthi Mendis, Coordinator, Chronic Diseases Prevention and Management.
The Committee had reviewed the use of oral forms salbutamol in 2009 and had concluded that (1) the inhaled route offers direct delivery to affected tissues and has a quicker onset of action and (2) inhaled salbutamol is effective in smaller doses than oral salbutamol and causes fewer adverse effects. However, it was decided to retain the oral forms with a note stating that such forms should only be used when inhaled treatment is not feasible.
The application focused on affordability of inhaled salbutamol and there were few new clinical data. Five trials and studies that compared oral and inhaled forms date from the 1970s and 1980s. All but one concluded to greater efficacy of the inhaled forms over the oral forms, while acknowledging superiority of oral forms over placebo. Similar efficacy between inhaled and oral forms required higher doses of oral salbutamol, leading to more adverse effects such as tachycardia, decreased oxygen saturation, flushing, hyperactivity, prolonged cough, and tremors. Adverse effects were dose dependent and dose limiting.
All current guidelines recommend inhaled salbutamol (symptom reliever) e.g. the Global Initiative on Asthma (GINA), NICE, SIGN (British Thoracic Society), the US Expert Panel Report 3 for the National Asthma Education and Prevention Program (NAEPP), and Australia, India, and Sri Lanka guidelines (1-9). Two guidelines mention that where inhaled salbutamol is not available, oral forms of salbutamol can be used; but all guidelines recommend the use of inhaled salbutamol as first or only choice. Inhaled salbutamol for symptom relief must be combined with anti-inflammatory treatment, either oral leukotriene antagonists, and/or inhaled steroids (systemically in severe forms) depending on the severity of asthma, to prevent complications and reduce exacerbation frequency or duration.
The Committee reviewed other indications for oral salbutamol. The application includes a selected review of three RCTs and two systematic reviews in children with wheezing and acute respiratory infections. Two trials in India and in Canada showed no difference between salbutamol and placebo for efficacy, but more adverse effects with oral short acting beta-agonists (10, 11), and a small third trial in Turkey showed that salbutamol brought no benefit over placebo in terms of hospitalization (12). Two systematic reviews concluded that bronchodilators were not effective and could not be recommended for routine use in the treatment of bronchiolitis and there was no benefit in bronchitis, with no effect on cough (13, 14).
The Committee acknowledged that salbutamol inhalation via a metered dose inhaler requires technical training to ensure proper use and hand-breathing coordination. In infants and children, the use of a spacer is recommended.
The Committee reviewed availability and cost data but noted that there are no direct comparative data of inhaled and oral forms of salbutamol. A bottle of salbutamol syrup covers only about 5 days of treatment whereas an inhaler delivers about 200 doses, corresponding to about 60 days of treatment and the immediate costs are higher for inhalers. The Committee however considered that short-term use is not in line with effective use of salbutamol in asthma, and that over the long term, inhalers might be more cost effective.
The Committee acknowledged that inhalers and spacers may not be available in resource-poor countries. This was based on data from 14 medical stores of central Africa showing availability of inhalers in 8/14 and of spacers in 1/14, and a higher price in the private sector (US$ 2.07–7.47) than in the public sector (US$ 1.30–7.25) (15). Similarly a survey in India found that inhalers were available in the public sector of 1/5 states and in only 2/20 public health facilities in that state, but cost was not an issue as medicines were delivered free of charge in the public sector. Availability was greater in the private sector (83–100%) and inhalers were available in all 5 states at about 0.86 to 0.96 times the international recommended price. A month’s treatment of inhaled beclomethasone and salbutamol would represent about 2 days’ wages of an unskilled government worker (16). The Committee noted the report on the availability of essential asthma medicines in 36 countries which concluded that availability varies 14–88.4% in the public sector and 47–79% in the private sector (17). The Committee also noted unpublished data showing that inhalers were available in only 3/8 teaching hospitals, but in 96% of private sector pharmacies in Sri Lanka.
The Committee acknowledged the affordability issue of salbutamol inhalers, but considered that oral salbutamol represents insufficient and inappropriate management of asthma and therefore recommended that oral salbutamol be deleted from the EML, with inclusion of a note to the effect that oral dosage forms only be considered in the absence of inhaled alternatives or the means to use them safely and effectively in the management of asthma.
1. Global strategy for the diagnosis and management of asthma in children 5 years and younger. Global Initiative for Asthma, 2009 (http://www.ginasthma.org/guidelines-gina-report-globalstrategy-for-asthma.html, accessed 30 September 2011).
2. GINA report, global strategy for asthma management and prevention. Global Initiative for Asthma, 2010 (http://www.ginasthma.org/guidelines-gina-report-global-strategy-for-asthma.html,accessed 30 September 2011).
3. The British Thoracic Society and the Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: quick reference guide. United Kingdom, 2008.
4. American National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and management of asthma full report, 2007. (http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf, accessed 29 September 2011).
5. Electronic therapeutic guidelines. Australia, 2009, Version 4 (http://www.tg.org.au/index.php?sectionid=49, accessed 21 September 2011).
6. Rai SP et al. Best treatment guidelines for bronchial asthma (India). Medical Journal Armed Forces India, 2007, 63(3): 264–268.
7. Management of asthma – guidelines. Sri Lanka Medical Association, 2006.
8. National best management guidelines – bronchial asthma. Sri Lanka College of Paediatricians, 2007.
8. WHO Pocket book of hospital care for children: guidelines for the management of common illnesses with limited resources. Geneva, World Health Organization, 2005 (http://whqlibdoc.who.int/publications/2005/9241546700.pdf, accessed 30 September 2011).
10. Gupta P et al. Oral salbutamol for symptomatic relief in mild bronchiolitis: a double blind randomized placebo-controlled trial. Indian Pediatrics, 2008, 45(7):547–553.
11. Patel H, Gouin S, Platt RW. Randomized, double-blind, placebo-controlled trial of oral albuterol in infants with mild-to-moderate acute viral bronchiolitis. Journal of Pediatrics, 2003, 142(5):509–514.
12. Cengizlier R et al. Effect of oral and inhaled salbutamol in infants with bronchiolitis. Acta Paediatrica Japonica, 1997, 39(1):61–63.
13. Gadomski AM, Bhasale AL. Bronchodilators for bronchiolitis. Cochrane Database of Systematic Reviews, 2006, (3):CD001266.
14. Smucny J, Becker LA, Glazier R. Beta2-agonists for acute bronchitis. Cochrane Database of Systematic Reviews, 2006, (4):CD001726.
15. Scottish Intercollegiates Guidelines Network (SIGN). Bronchiolitis in children — a national clinical guideline. NHS Quality Improvement Scotland, 2006.
16. Robertson J et al. What essential medicines for children are on the shelf? Bulletin of the World Health Organization, 2009, 87(3):231–237.
17. Kotwani A. Availability, price and affordability of asthma medicines in five Indian states. The International Journal of Tuberculosis and Lung Disease, 2009, 13(5):574–579.