Asthma Management Handbook

Considering other regular treatments in children 6 years and over

Recommendations

Do not routinely prescribe theophyllines (aminophylline or theophylline) for children aged 6 years and over.

Note: Theophyllines are sometimes prescribed by specialists for children with difficult-to-control asthma.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Ipratropium is not recommended for the regular management of asthma in children.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available), with particular reference to the following source(s):

  • McDonald et al. 20031

More information

Ipratropium for children

Cochrane systematic reviews concluded that, overall, clinical trial evidence does not support the regular use of muscarinic antagonists (anticholinergic bronchodilators) in the maintenance treatment of asthma in children (i.e. outside the context of acute asthma).1

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Inhaled corticosteroid/long-acting beta-2 agonist combinations for children: 6 years and over

Available combinations

Three combinations of inhaled corticosteroid and long-acting beta2 agonist in a single inhaler are currently available:

  • The combination of fluticasone propionate and salmeterol xinafoate in a single inhaler is registered for use in children aged 4 years and over.2
  • The combination of budesonide and formoterol in a single inhaler is registered for use in children aged 12 years and older.3
  • The combination of fluticasone propionate and formoterol in a single inhaler is TGA-registered for use in children aged 12 years and older.4

Role of combination therapy in children

Evidence from clinical trials does not support the use of combination therapy with a long-acting beta2 agonist plus an inhaled corticosteroid as initial preventer treatment in children who are not already taking inhaled corticosteroids.56

Combination therapy is a step-up option for some children whose asthma is not well controlled by low-dose inhaled corticosteroids alone.

Beta2 receptor regulation

Clinical response to long-acting beta2 agonists partly depends on genetics. A beta2 receptor genotype  (Arg16 polymorphism in the beta2 receptor gene) pre-disposes children with asthma to down-regulation of the beta2 receptor and increased susceptibility to flare-ups during regular treatment with long-acting beta2 agonists.7 However, routine genetic testing to tailor asthma therapy is not yet available in clinical practice.

Systematic reviews and meta-analyses have led to concern about the possibility that the use of long-acting beta-agonists (even in combination with inhaled corticosteroids) might even increase the risk of flare-ups that require treatment with oral steroids or hospital admission, or of severe flare-ups.8, 9, 10  A meta-analysis by the US Food and Drug Administration found that the use of long-acting beta2 agonists was associated with increased risk of severe asthma-associated adverse events (both overall and among the subset of people using concomitant inhaled corticosteroid and long-acting beta2 agonist), and that this risk was greatest in children aged 4–11 years.10

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References

  1. McDonald N, Bara A, McKean MC. Anticholinergic therapy for chronic asthma in children over two years of age. Cochrane Database Syst Rev. 2003; Issue 1: CD003535. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003535/full
  2. GlaxoSmithKline Australia Pty Ltd. Product Information: Seretide (fluticasone propionate; salmeterol xinafoate) Accuhaler and MDI. Therapeutic Goods Administration, Canberra, 2013. Available from: https://www.ebs.tga.gov.au/
  3. AstraZeneca Pty Ltd. Product Information: Symbicort (budesonide and eformoterol fumarate dihydrate) Turbuhaler. Therapeutic Goods Administration, Canberra, 2010. Available from: https://www.ebs.tga.gov.au/
  4. Mundipharma Pty Ltd. Product Information: Flutiform (fluticasone propionate and eformoterol fumarate dihydrate). Therapeutic Goods Administration, Canberra, 2013. Available from: https://www.ebs.tga.gov.au
  5. Ni Chroinin M, Greenstone I, Lasserson TJ, Ducharme FM. Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults and children. Cochrane Database Syst Rev. 2009; Issue 4: CD005307. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005307.pub2/full
  6. Ducharme FM, Ni Chroinin M, Greenstone I, Lasserson TJ. Addition of long-acting beta2-agonists to inhaled steroids versus higher dose inhaled steroids in adults and children with persistent asthma. Cochrane Database Syst Rev. 2010; Issue 4: CD005533. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005533.pub2/full
  7. Lipworth BJ, Basu K, Donald HP, et al. Tailored second-line therapy in asthmatic children with the Arg(16) genotype. Clin Sci (Lond). 2013; 124: 521-528. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23126384
  8. van Asperen PP, Mellis CM, Sly PD, Robertson C. The role of corticosteroids in the management of childhood asthma. The Thoracic Society of Australia and New Zealand, 2010. Available from: http://www.thoracic.org.au/clinical-documents/area?command=record&id=14
  9. van Asperen PP. Long-acting beta agonists for childhood asthma. Aust Prescr. 2012; 35: 111-3. Available from: http://www.australianprescriber.com/magazine/35/4/111/3
  10. McMahon AW, Levenson MS, McEvoy BW, et al. Age and risks of FDA-approved long-acting β2-adrenergic receptor agonists. Pediatrics. 2011; 128: e1147-1154. Available from: http://pediatrics.aappublications.org/content/128/5/e1147.long