Two Food and Drug Administration officials who work in the safety division of the FDA said four popular asthma drugs raise the death risk of users with the highest incidence in children. The four drugs in question are GlaxoSmithKline PLC's Serevent and Advair, Novartis AG's and Schering-Plough Corp.'s Foradil and AstraZeneca PLC's Symbicort. These drugs fall into a class of medications known as long-acting beta-agonists, or LABAs, and have been the subject of an ongoing FDA safety review.

The analysis involved 110 trials and 60,954 patients with the bulk of the patients were from Serevent trials, with about 43,000 patients, the agency said. This was prepared for an advisory committee meeting scheduled next week to discuss the safety of the drugs as a class and the panel will vote on whether the drugs should continue to be marketed for children and adults.

The report examined if the drugs increased a combined measure of asthma-related death, hospitalization and asthma-related intubation, or the placement of a tube in patients' noses or mouths to help them breathe. The agency said there were 20 asthma-related deaths in the studies and of those, 16 were patients on Serevent and four were patients in the non-LABA group.

It is apparent from the Agency memos released along with the analysis that the agency is divided over what course of action to take. The FDA's drug safety division is recommending that the drugs not be marketed for children, and in some cases adults, while the agency's pulmonary division stated that removing the products from the market would be "extreme." Dr. Badrul A. Chowdhury, director of the division of pulmonary and allergy products at the agency, in his own assessment cautioned that the risk of death associated with the drugs was small and that banning their use “would be an extreme approach” that could lead asthmatics to rely on other risky medications. Though irrespective of the agency’s decision the drugs will remain in the market the agency’s drug-safety officials concluded that they were useful in patients suffering from chronic obstructive pulmonary disease, nearly all of whom are elderly. The division said that the drugs already carried a black box warning while the pulmonary division said the asthma-related deaths are "numerically small".

The agency said in an overview its analysis showed "that LABAs were associated with an increased risk of asthma-related events relative to non-LABA treatment as measured by the asthma composite endpoint consisting of asthma-related death, asthma-related intubation and asthma-related hospitalizations."

Dr. Katharine Knobil, global clinical vice president for Glaxo said the agency’s conclusions are “not supported by their own data,” adding that Advair was safe and that Serevent was safe when used with a steroid. Michele Meeker, a spokeswoman for AstraZeneca, said that most studies of Symbicort had been excluded by the F.D.A.’s safety division in its analysis and on reviewing all the information it showed that the drug does not increase the risks of death or hospitalization.

Dr. Daniel Frattarelli, a Detroit pediatrician and member of the American Academy of Pediatrics’s committee on drugs said, “Most of us felt these were pretty good drugs. I’m really looking forward to hearing what the F.D.A. committee decides.”