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I read with interest the article Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom by Todd et al and the accompanying editorial in the December issue of Archives.
In the reported cases, the children had been administered substantially (up to 5 times) higher than the Glaxo SmithKline (GSK) Core Data Sheet recommended Flixotide dose of 400 mcg/day and use of fluticasone (FP) at such doses is certainly not endorsed by GSK. Within the recommended doses, there are a wealth of data from controlled clinical trials that Flixotide is a well tolerated and effective drug in adults and children.1–5 There are a number of recent studies in children which identified no cases of adrenal crisis and no effect on growth following 12 months treatment with FP at licensed doses.6–8
There are also a number of methodological deficiencies in this survey, the most important being that the survey is not case-controlled and lacks information on true incidence against the overall FP use or exposure. In addition, it is unclear from the survey what attempts were made to closely monitor any adrenal suppression with increasing doses of FP or whether patients were down-titrated to the lowest effective FP dose, as routinely recommended.
The survey data also imply that fluticasone has been implicated in the great majority of cases of adrenal failure even though it is the least frequently prescribed form of inhaled corticosteroid. Prescribing data in relation to fluticasone from the UK DINLINK (Doctors Independent Network) database, shows that it is in fact the most commonly prescribed inhaled corticosteroid in children with moderate and severe asthma.9 DINLINK is an amalgamated database of the anonymised computer records of a panel of 300 general practitioners spread across the UK selected to represent the demographic population of the UK.
In addition, the authors’ contention that adrenal effects with FP are due to its greater lipophilicity and hence accumulation over prolonged periods is misconceived and inaccurate. There are studies to show that there is no accumulation of FP at a steady state.10 It is the clearance value which determines the amount of FP in the body at steady state, and lipohilicity per se in not a relevant factor.11
I also wanted to take this opportunity to comment on the editorial by Dr Russell. The last line of the editorial recommends that if high dose inhaled corticosteroid is considered necessary, that it is advisable not to use fluticasone. The recent publication by the CSM “Current Problems in Pharmacovigilance”12 states that adrenal suppression is a dose related class effect of inhaled steroids, and that all inhaled corticosteroids are associated with an increased risk of adrenal crisis when used at higher than licensed doses.
In conclusion, inhaled corticosteroids have an important place in asthma management throughout the world, and this paper by Todd et al should be reviewed in this context. Any inhaled corticosteroid used at such high doses has the potential to cause systemic effects, and paediatricians should be encouraged to treat their patients using the lowest effective dose, down-titrating as appropriate.
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