FDA Panel Expresses Safety Concerns about Asthma Drugs
December 22, 2008
(Please note that the following information pertains to Asthma, and is not a COPD issue.)
This week, the FDA held a joint meeting of the Pulmonary Allergy Drug Advisory Committee and Pediatric Advisory Committee to review the safety and efficacy of long-acting beta agonists (LABA) for the treatment of asthma.
The advisory panel voted to remove the asthma indication in all age groups for two single- agent LABA products; salmuterol [should be salmeterol] (produced by GSK as Serevent) and formoterol (produced by Novartis as Foradil). Although the recommendations of the FDA advisory panel of outside experts are not binding, the FDA generally follows the experts’ recommendations.
In related action, the panel voted to maintain the current asthma indication for two inhaled corticosteroids/LABA products: fluticasone propionate/salmeterol (Advair by GSK) for ages > 4, and budesonide/formoterol (Symbicort by AstraZeneca) for ages > 12.
The data that the FDA advisory panel reviewed centered on studies and meta-analyses that suggest that a higher number of severe adverse outcomes are associated with LABA use, including asthma-related hospitalizations and deaths. FDA staff members were divided on how to respond to the safety concerns. Staff in the FDA’s Office of Surveillance and Epidemiology recommended:
- Withdrawing the asthma indication form all LABAs for individuals < 18 years of age
- Removing the asthma indication and contraindicating the use of single entity LABA for all ages
- Removing the asthma indication for combined inhaled corticosteroids/LABAs (Advair and Symbicort) Conversely, staff at the FDA Center for Drug Evaluation and Research – Pulmonary Allergy Products
Division recommended:
- Products containing LABA should continue to be marketed for asthma (both single agent LABA and LABA/ICS products)
- Safety risks should be managed through labeling
ATS member Al Munzer, M.D., presented the comments of the ATS to the FDA advisory committee. The ATS comments were drafted by a panel of asthma experts. The ATS recommended the following:
- Long-acting beta agonists in combination with inhaled corticosteroids should remain on the market for the treatment of asthma
- Single-agent LABA products should remain on the market for asthma
- Any changes or enhancements to the existing black box warning for LABA should be consistent with the NIH/NHLBI-sponsored National Asthma Education and Prevention Program: Expert Panel Report 3 (NAEPP EPR 3) recommendations
- Any changes to the label indications for LABA should be for asthma only.
- Further research is needed on the safety and efficacy of LABAs.