[Fluticasone propionate in children and infants with asthma].
The known efficacy of fluticasone propionate in adults, comparable at half-dosage of corticosteroids has been validated by the market authorization (MA) and by the national and international guidelines for beclomethasone. This could be partly explained by its pharmacological properties, affinity for glucocorticosteroid receptors, lung deposition and lipophilicity. The limited systemic adverse events is due to its low bioavailability, optimal hepatic clearance, high plasma protein binding. The efficacy in asthmatic children has been confirmed in clinical studies showing a "plateau" efficacy between 100 and 200 microg/d for the majority of children. Most children are controlled by such dosages: the added value of increasing posology on asthma control exists but is small. A high off-label posology does not allow more quickly asthma control and therefore is not justified. A twice daily dosing is more efficient, particularly for initiation of maintenance therapy, than a once daily dosing. A literature survey confirms that, at MA recommended daily doses in children (100-200 microg), fluticasone propionate has no clinically significant effect either on hypothalamic-pituitary-adrenal (HPA) axis (basal function or stimulation tests), bone or growth velocity. However, high daily doses (higher to 500 microg/day) for long periods expose to systemic adverse effects with measurable consequences on growth rate, bone density (decreasing biochemical makers of bone formation) and HPA function. Several cases of adrenal insufficiency that may have led to acute adrenal crisis have been reported in 4- to 10-year-old children receiving fluticasone propionate in doses between 500 to 2000 microg daily. In case of surgery or infection, a preventive treatment of adrenal insufficiency with hydrocortisone should be proposed for children treated for more than 6 months with such high daily doses. Such children need definitely an advice from paediatricians specialized in chest diseases as well as in endocrinology. It is important to recall that the clinical benefit of daily doses of inhaled corticosteroids higher than recommended is low and that the good use of inhaled corticosteroids particularly in children lays on the careful search of the minimal efficient daily doses.
Marchac
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V
Service de pneumologie et d'allergologie pédiatrique, hôpital Necker-Enfants-Malades, Assistance publique-Hôpitaux de Paris, 149 rue de Sèvres, 75743 Paris cedex 15, France. v.marchac@cmsea.com
Foussier
V
V
Devillier
P
P
Le Bourgeois
M
M
Polak
M
M
D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001249:Asthma / Q000097:blood / Q000188:drug therapy*; D001507:Beclomethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001682:Biological Availability; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000068298:Fluticasone; D006801:Humans; D007223:Infant; D017410:Practice Guidelines as Topic
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D000068298:Fluticasone; D001507:Beclomethasone