Inhaled corticosteroids and adrenal suppression in adults and children

In adults (1):

• adrenal suppression due to systemic absorption with high doses - greater than 1500 mcg beclomethasone diproprionate or equivalent per day
  • marked adrenal suppression occurs with doses >1500 micrograms/day (>750 micrograms/day for fluticasone), although there is a considerable degree of inter-patient susceptibility (2)
• treatment with systemic steroids should be considered during periods of stress or elective surgery in patients who have had prolonged therapy with high dose inhaled steroids

In children (3):

• prescribers are warned that the presenting of symptoms of adrenal suppression and crisis are non-specific and include anorexia, abdominal pain, weight loss, nausea, headached, vomiting, decreased level of consciousness, hypogylcaemia and seizures. Situations which may potentially trigger acute adrenal crisis include trauma, infection, surgery or any rapid reduction in dosage
• all inhaled steroids are associated with an increased risk of adrenal crisis when used at higher than licensed doses but prescribers are reminded that fluticasone shold normally be used at half thedose of beclomethasone (CFC containing) or budesonide because of its greater potency
  
  
  
• the British Guideline on the Management of Asthma recommends that  
  • in children under five years (4)
    • the dose of ICS should not exceed 400mcg/day beclometasone dipropionate (BDP) or equivalent (e.g. 400mcg/day budesonide, or 200mcg/day fluticasone propionate)
  • in children aged five to 12 years
    • the dose should not exceed 400mcg/day BDP or equivalent, unless the patient's asthma remains uncontrolled despite add-on therapy (initially a long-acting ß2-agonist, followed by trials of other therapies e.g. a leukotriene receptor antagonist or sustained-release theophylline)
      • in such cases the dose may be increased to 800mcg/day BDP or equivalent
      • however, higher, unlicensed doses of ICS should only be initiated and supervised by specialists, and therapy should be reviewed regularly and titrated down to the lowest dose at which effective control of asthma is maintained
  • steroid treatment cards should be issued routinely for patients, including children, who require prolonged, high, unlicensed doses of ICS, because they may need corticosteroid cover during an episode of stress (e.g. an operation) (5)
• prescribers are reminded that:
• it is important to review therapy regularly and titrate down to the lowest dose at which effective control of asthma is maintained
• if a doctor considers that a child's asthma is not controlled on the maximum licensed dose of their inhaled corticosteroid, despite the addition of other therapies, the child should be referred to a specialist inn the management of paediatric asthma

Notes:

• MeReC note that (2)
  • in children, high doses of ICSs >=400 micrograms/day (>=200 micrograms/day for fluticasone) may be associated with systemic side effects, including growth failure and adrenal suppression
  • dose of ICS required to put a child at risk of clinical adrenal insufficiency is unknown, but this is likely to occur at >=800 micrograms/day (>=400 micrograms/day for fluticasone)
  • majority of cases of clinical adrenal insufficiency have related to fluticasone and although rare, this adverse effect is serious and potentially life threatening
  • children treated with >=800 micrograms/day (>=400 micrograms/day for fluticasone) should be under the care of a specialist paediatrician for the duration of high dose treatment and their asthma management plan should include specific advice about steroid replacement during severe intercurrent illness
  • for children under 5 years of age, referral to a specialist paediatrician should be considered at lower ICS doses

Reference:

• (1) Drug and Therapeutics Bulletin (2000), 38(1),1-5.
• (2) MeReC Bulletin 2008; 13(2).
• (3) Current Problems in Pharmacovigilance (2002), 28,7.
• (4) Scottish Intercollegiate Guidelines Network/The British Thoracic Society. British Guideline on the Management of Asthma. Revised edition November 2005.
• (5) MeReC Extra March 2007.