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      Growing debate regarding the safety of long-acting beta2 agonists for the treatment of asthma

Recommendations from Europe awaited

16 November 2005
Corrected 8 December 2005

IPCRG POSITION STATEMENT

In 2003 the UK Medicines and Healthcare products Regulatory Agency (MHRA) acknowledged concerns regarding safety of long acting beta2 agonists, and have issued cautionary advice, which has now been incorporated into national guidelines. In 2005 the U.S. Food and Drug Administration (FDA), 'Health Canada' and some pressure groups have commented on the issue, held enquiries and further clarified advice on the appropriate use of these medications. The European Medicines Agency (EMEA) has yet to make comment, and the full EMEA recommendations paper has yet to be published, but the IPCRG felt it important to give this position statement that it will review in the light of any further evidence or policy directive.

An FDA Committee and 'Health Canada' both reviewed the 2003 Salmeterol Multi-centre Asthma Research Trial, known as SMART, which investigated asthma medication containing salmeterol: a long-acting beta2 agonist.

The SMART study of about 30,000 patients in the USA was prematurely halted in January 2003 after early results suggested an increased risk of asthma-related death in patients taking salmeterol (as compared to a placebo) in addition to their usual asthma therapy. Although not conclusive, the study suggests that any risk, if it exists, may be higher in those who were not being treated with inhaled corticosteroids at the start of the study and also in African-American patients. This data is yet to be subject to peer review and until it is we rely on interpretation by the regulatory bodies.

In July 2005 an FDA advisory committee reviewed the data from the SMART trial and voted to keep LABAs on the market. However, they recommended that the FDA require a comparable black-box warning on formoterol's label, to that carried by products containing salmeterol.

As a result of the FDA review, 'Health Canada' issued an advisory statement about the possible increased risks of asthma-related deaths associated with the use of LABAs*:

  • Salmeterol and formoterol can only be used with an appropriate dose of inhaled corticosteroid as determined by a physician.
  • Long-acting beta-2 agonists are not a substitute for inhaled or oral corticosteroids.
  • Serevent, Foradil or Advair should never be used to treat acute or sudden onset of asthma symptoms and attacks.
  • Symbicort is not indicated for the treatment of sudden asthma symptoms and attacks.
  • Oxeze may be used to treat acute, or the sudden onset of asthma symptoms, in patients 12 years and older.
  • Medical attention should be sought if a patient's use of asthma medications becomes less effective, or if more inhalations than usual are required.
  • Patients must not stop or reduce their asthma therapy without first consulting their prescribing physician. Abruptly stopping medications may result in deteriorating asthma control, which can be life-threatening.
  • Patients with asthma who have any questions about their current prescription or treatment should contact their physician or pharmacist directly.

'Health Canada' is engaged in an ongoing review of existing safety data and has also requested that manufacturers of these medications inform physicians of the SMART study findings and of the outcome of the FDA advisory committee meeting. Pending advice from European and other regulatory authorities, health professionals may like to consider following 'Health Canada's' guidelines when using LABAs within the context of local guidelines and regulations and to remember the importance of anti- inflammatory therapy in asthma.

16 November 2005
Corrected 8 December 2005

End

Update
13 December 2005

In November 2005 both the US FDA and the UK's MHRA individually issued statements regarding the safety of the use of LABAs. In light of this practitioners are advised to check licensing arrangements in their own country as there are local differences in regulation. The IPCRG also recommends that local policy makers are approached for guidance where none exists.

For more information refer to:

For further information on the FDA committee enquiry please refer to their website: http://www.fda.gov/ohrms/dockets/ac/05/transcripts/2005-4148T1.htm

For further information on the 'Health Canada' advisory please refer to their website: http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/2005/2005_107_e.html

Committee on Safety of Medicines and Medicines and Healthcare products Regulatory Agency. Current Problems in Pharmacovigilance Salmeterol and formoterol in asthma management. 2005; 29: 5 available from http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&useSecondary=true&ssDocName=CON007449&ssTargetNodeId=368

* Please note that these recommendations apply to the use of beta2 agonists in the treatment of asthma and do not apply to the treatment of COPD.

The IPCRG welcomes comments on its position statements. Please direct any comments to our Secretariat:
Email: tricia@redhotirons.com
Postal address:
 Tricia Bryant
Smithy House
Waterbeck
Lockerbie
Scotland DG11 3EY
United Kingdom

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