MHRA review of formoterol and salmeterol in asthma and chronic obstructive pulmonary disease

29 August 2008

Important clinical research on long-acting beta2 agonists, which are used to treat asthma and chronic obstructive pulmonary disease (COPD), has become available in recent months.  More information on the research can be found under:
› Asthma: Long-acting β2 agonists

In December 2006, the MHRA issued updated information on the use and safety of the two long-acting beta2 agonists, formoterol and salmeterol.  The update also stated that the Commission on Human Medicines (CHM) and its Pharmacovigilance Expert Advisory Group had recommended a full review of the overall balance of risks and benefits of using long-acting beta2 agonists in asthma and COPD.

The review to address the use of long-acting beta2 agonists in asthma and in COPD has drawn on recently completed research.  The initial review of long-acting beta2 agonists in asthma was completed in November 2007.

Formoterol is an ingredient in the following proprietary products: Atimos Modulite, Foradil, and Oxis Turbohaler; it is combined with budesonide in Symbicort Turbohaler and with beclometasone in Fostair. Salmeterol is an ingredient in the following proprietary products: Serevent Accuhaler, Serevent Diskhaler, and Serevent Evohaler; it is combined with fluticasone propionate in Seretide Accuhaler and Seretide Evohaler.

What specifically has the MHRA examined about formoterol and salmeterol?
The MHRA built on the considerable information it already had on formoterol and salmeterol.  A detailed review of safety and appropriate use of these drugs focused specifically on the following issues:

• Identifying new research on the safety and effectiveness of long-acting beta2 agonists.
• In the case of asthma, finding out how inhaled corticosteroid influence the effects of formoterol and salmeterol.
• Determining if there is any difference between formoterol and salmeterol in the way they work.
• How the clinical effects of formoterol and salmeterol change with different doses.
• How these medicines are used in UK clinical practice and how the management of asthma has changed since formoterol and salmeterol were introduced.
• Whether genetic differences significantly affect the response to long-acting beta2 agonists.

Who reviewed the information on formoterol and salmeterol?
The MHRA review was guided by independent clinical and scientific experts from the Commission on Human Medicines and its expert advisory groups.

Manufacturers of long-acting beta2 agonists were asked to supply information on the specific issues being addressed by the review.  Further ongoing research was identified by MHRA assessors.

The MHRA informed the British Thoracic Society (BTS) and the Scottish Intercollegiate Guidelines Network (SIGN) about its review of long-acting beta2 agonists. The BTS/SIGN guidance on asthma has recently been updated. 

What has happened so far?
The updated information issued in December 2006, and the advice issued by the CHM is now reflected in the product information. Following completion of the initial phase of the review the CHM concluded that the data supported the use of LABA in conjunction with inhaled corticosteroids for moderate to severe asthma as recommended by the latest BTS/SIGN guideline on the management of asthma. An article in the Drug Safety Update informed prescribers of the conclusions and reinforced the advice that long-acting beta2 agonists should always be used in conjunction with inhaled corticosteroids.

What will happen next?
The MHRA is now reviewing the use of long-acting beta2 agonists for the management of asthma in children under 12 years of age. The findings of this review will be included in a future issue of Drug Safety Update. The review of long-acting beta2 agonists in COPD will follow completion of the review in asthma.