FDA advisers back stronger flu drug warnings

By Kim Dixon

GAITHERSBURG, Maryland (Reuters) - U.S health advisers recommended on Tuesday stronger warnings on the labels of flu drugs made by Roche Holding AG and GlaxoSmithKline Plc, amid reports of abnormal and, in the case of the Roche drug, sometimes fatal psychiatric behavior.

The U.S. Food and Drug Administration advisory panel reviewed the small but rising number of cases, mostly in Japan, of patients taking Roche's Tamiflu and Glaxo's Relenza who have experienced hallucinations and delirium.

In the case of Tamiflu, some cases of erratic behavior, including jumping from buildings, resulted in deaths.

Although no direct link with the antiviral drugs has been established, the advisory panel recommended adding the new case reports to the drugs' labels. The FDA typically takes the advice of its advisory panels.

The meeting was the third public review of flu drug safety, originally prompted by reports two years ago of a dozen deaths, including suicide, of children in Japan who took Tamiflu.

"The public expects to be made aware. I never hear on the public side, that they are getting too much information," said Dr. Michael Fant, a pediatric expert at the medical school at the University of Texas, and panel member.

"If we're still wrestling with it, to me even though we don't have anything definitive, that in and of itself warrants conveying those concerns to the public."

In March, Japan warned against prescribing Tamiflu to those aged 10 to 19 after reports of mostly young people showing signs of strange and erratic behavior after taking the drug.

FDA staffers have recommended a stronger label warning for Tamiflu to note patient deaths. For Relenza, addition of a warning about hallucinations and delirium is recommended.

Several panel members said that noting the fatalities in patients taking Tamiflu was appropriate in a new label, although a formal vote on that issue was not taken. The panel voted to generally note the newly reported cases of neuropsychiatric behavior seen with Relenza.

LINK UNCLEAR

Many of the experts said it should be noted that some unusual behavior was observed in flu patients who did not take the drugs, suggesting a possible link to the disease itself.

FDA staffers described reports of about 700 cases of psychiatric adverse events for both drugs, and 25 cases of pediatric deaths in patients taking Tamiflu, reported to the agency through May 2007. No fatalities were reported for Relenza.

Three of the deaths occurred in the United States, and causes included complications of flu.

Glaxo and Roche officials said they opposed label changes and cited data showing no causal link between the drugs and adverse events. It is "very difficult to differentiate drug from disease," Dr. Jonathan Solsky of Roche told the panel.

About 48 million people worldwide have taken Tamiflu since it was approved in 1999, according to Roche. Relenza has been used by about 4 million people since its launch in 1999.

The flu virus is a major cause of death and illness in the United States. Complications from the illness kill about 36,000 Americans a year, a government expert told the panel. Children and the elderly are especially at risk.

One panel member said the benefits of Tamiflu are slim compared with the risks, however rare and uncertain.

"When we give Tamiflu to children who have influenza, we shorten (the duration of flu) by one day, a day and a half," said Dr. Keith Kocis, a pediatric care doctor at the North Carolina Women's Hospital, and an advisory panel member. "To me (the benefit is) relatively minor."

Dr. David Kimberlin of the University of Alabama in Birmingham was in the minority when he warned against scaring the public, given the uncertainty about cause and effect.

"People are going to hear death" and assume causality, he said. "I think it's allowing an overstatement."

(Reporting by Kim Dixon; editing by Andre Grenon and Tim Dobbyn)