What do I need to know when prescribing a long-acting beta2-agonist?
- The long-acting beta2-agonists (LABAs), salmeterol and formoterol, are well tolerated and have few adverse effects.
- There has been concern regarding LABAs and an increase in asthma-related adverse events. On the basis of current evidence, the Medicines and Healthcare products Regulatory Agency has issued the following recommendations [MHRA, 2005]:
- Long-acting beta2-agonists (LABAs) should not be prescribed for someone who is not already using an inhaled corticosteroid.
- Inhaled corticosteroid treatment should not be stopped whilst the person is using a LABA.
- People with acutely deteriorating asthma should not be started on LABA therapy.
- People should be monitored closely, especially during the first 3 months of treatment.
- Treatment with LABAs should be continued only if they have shown benefit.
- Stepping-down therapy should be considered when good long-term asthma control has been achieved.
- Salmeterol has a slower onset of action than salbutamol or terbutaline and should not be used to relieve an acute exacerbation of asthma [BNF 53, 2007].
- A daily dose of 24 micrograms formoterol should be sufficient for most children, particularly younger age groups. Higher doses should be used rarely, and only when control is not maintained on the lower dose [MHRA, 2010].
Basis for recommendation
- There has been concern regarding the safety of long-acting beta2-agonist (LABA) therapy.
- The Salmeterol Multi-Centre Asthma Research Trial (SMART) [Nelson et al, 2006] was a large randomized controlled trial (n = 26,355) that compared salmeterol with placebo in older children and adults. The study was stopped prematurely because the incidence of asthma-related adverse effects (such as severe asthma exacerbations and asthma-related deaths) was higher in people who had used salmeterol without an inhaled corticosteroid (ICS):
- The risk of adverse effects was higher in African-American people than in the white population.
- The authors could not determine whether the negative outcomes in the trial were due to the physiological effect of the drug, genetic factors, behavioural factors, or combinations of these factors.
- A meta-analysis pooled the results from 19 trials (n = 33,826 including the SMART study), and similarly concluded that LABA therapy increases severe and life-threatening asthma exacerbations, and risk of asthma-related death [Salpeter et al, 2006].
Using a long-acting beta2-agonist
- Advise people who are starting treatment with a long-acting beta2-agonist (LABA) to report any deterioration in symptoms [BNF 53, 2007].
- Advise people using a LABA that they must not stop using their inhaled corticosteroid (ICS).
- Advise people who have been prescribed salmeterol that they should not use it to relieve an acute asthma attack.
- Advise people who are inhaling terbutaline using a turbohaler to rinse their mouth after each use. A fraction of the dose will always be deposited in the mouth and rinsing the mouth will minimize the amount of terbutaline absorbed systemically [ABPI Medicines Compendium, 2011b].