FDA质疑儿童哮喘药安全

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FDA Questions the Safety Of Asthma Drugs for Kids
By JENNIFER CORBETT DOOREN and ANNA WILDE MATHEWS
November 24, 2007

http://online.wsj.com/article/SB ... hoo_hs&ru=yahoo

WASHINGTON -- Food and Drug Administration drug-safety reviewers questioned whether the GlaxoSmithKline PLC asthma drugs Serevent and Advair are appropriate for use in pediatric patients, and said the issue needs further review.
The asthma-drug findings came in documents posted Friday in advance of a meeting of the FDA's pediatric advisory committee. The session, which starts Tuesday, is expected to focus on the safety of a number of drugs, including the influenza medications Tamiflu, from Roche Holding AG, and Relenza, made by Glaxo.
Serevent and Advair, which both contain the active ingredient salmeterol, already carry a strong \"black box\" label warning about a risk of asthma-related death. The agency's reviewers said they hadn't identified side effects unique to children.
While the FDA staff memo said the review was limited by the small number and incomplete nature of some potential side-effect reports, the staffers still \"conclude that salmeterol may have an unfavorable risk-benefit ratio in the treatment of pediatric asthma.\" They wrote that there was evidence inhaled steroid therapy, sometimes taken to protect against possible danger linked to salmeterol, was \"not protective\" in young people taking a similar drug, Novartis AG's Foradil. The reviewers suggested a more in-depth safety review of salmeterol that would also include Foradil.
The FDA staffers found five deaths among nine adverse-event reports in children during its 13-month review period of Serevent. Three of the nine cases were associated with overdoses of Serevent, the FDA documents said. Such reports from the FDA's adverse-event system, however, don't mean a particular drug definitely caused a problem, and asthma itself can cause death.
Glaxo said it believed Serevent and Advair were appropriately labeled to reflect the safety profile of the products. The company also said \"salmeterol continues to exhibit a favorable safety profile in pediatric subjects and the safety profile is similar to that seen in adults.\"
FDA safety reviewers also suggested that both Tamiflu and Relenza should get label updates with information about neuropsychiatric events, such as hallucinations, reported occasionally among users. Tamiflu already has a label precaution about this potential side effect, which drew attention two years ago after reports of 12 deaths and about three dozen neuropsychiatric events in Japan in 2000 to 2005.
More recent reports of similar episodes in young patients still \"provide conflicting evidence as to whether these events are drug related only, disease manifestation alone, or a combination of drug-disease expression,\" the FDA safety reviewers said in a memo. Still, the staffers wrote, it \"seems prudent\" for the labeling of both products to include language about reports of hallucinations, delirium and abnormal behavior.
Roche, in a document also posted to the FDA's Web site, said that the company believes the current labeling language remains appropriate. However, Roche spokesman Terry Hurley said Roche is \"open\" to considering a label change if the FDA thinks more details are needed. Roche also said there's no increased risk of neuropsychiatric events in influenza patients treated with Tamiflu compared with untreated influenza patients.
Glaxo said it didn't see a potential neuropsychiatric signal until a cluster of reports from Japan surfaced in March. However, the company said there's no evidence the events were caused by Relenza, and it doesn't believe a labeling change is needed.
Separately, Glaxo said Friday that new data from a European clinical trial have shown its candidate vaccine Rotarix is effective at preventing rotavirus gastroenteritis during the first two years of life. The company said results from the trial of almost 4,000 infants indicated Rotarix was 79% effective against rotavirus gastroenteritis of any severity, 90% effective against severe forms, and 96% effective against hospitalizations.
Glaxo said the data, published in British medical journal the Lancet, show its vaccine effectively prevented the infection, which causes severe dehydration and diarrhea in infected children.