Government health regulators recommended adding label precautions about neurological problems seen in children who have taken flu drugs made by Roche and GlaxoSmithKline.
The Food and Drug Administration on Friday released its safety review of Roche’s Tamiflu and Glaxo’s Relenza. Next week, an outside group of pediatric experts is scheduled to review the safety of several such drugs when used in children.
FDA began reviewing Tamiflu’s safety in 2005 after receiving reports of children experiencing neurological problems, including hallucinations and convulsions.
Twenty-five patients under age 21 have died while taking the drug, most of them in Japan. Five deaths resulted from children “falling from windows or balconies or running into traffic.”
There have been no child deaths connected with Relenza, but regulators said children taking the drug have shown similar neurological problems.
While FDA said it isn’t clear whether the problems are directly related to the drugs, it recommends adding language about the possible side effects to labeling for physicians who prescribe Tamiflu and Relenza.
In documents prepared for the meeting next week and posted on the FDA's Web site, agency staff recommended that Tamiflu's label be strengthened to note: "In some cases, these behaviors resulted in serious injuries, including death, in adult and pediatric patients."
The FDA staff also reviewed Relenza, a drug in the same class as Tamiflu, recommending its label be changed to note "reports of hallucinations, delirium and abnormal behavior" observed in some patients taking the drug.
The current Relenza label has no label warning related to psychiatric events.
The FDA staff said the evidence is "conflicting" as to whether the events are medication-related, a manifestation of disease or a combination of the two.
Tamiflu has been more widely used in Japan than in the United States, and there is some evidence that the Japanese are more vigilant about reporting side effects, the FDA has said.
Tamiflu, known generically as oseltamivir, is a pill, while Relenza, generically zanamivir, is inhaled.
A Roche spokesman said no causal relationship between Tamiflu and these psychiatric events has been proven.
"Roche has extensively investigated the issue and is conducting ongoing clinical and nonclinical studies. Roche takes all adverse events reports very seriously," spokesman Terence Hurley said in a statement.
Besides being a drug side effect, the agency said the behaviors alternately could result from an unusual strain of flu or a rare genetic reaction to the drug.
About 48 million people have taken Tamiflu worldwide, including 21 million children, since approval in 1999, he said.
A Glaxo spokeswoman said a review of premarketing and post-approval trial data showed no worrying safety signals on patients taking Relenza. The drug is a not a major revenue-generator for UK-based Glaxo.
FDA staff based its recommendations on a review of nearly 600 cases of neuropsychiatric events reported by patients on Tamiflu and 115 cases of such events by patients taking Relenza.
The FDA staff will present the advice to the advisory panel of experts meeting on Tuesday, November 27. The agency typically takes the advice of these panels but is not bound by them.
Japan in March warned against prescribing Tamiflu to those ages 10 to 19 as more than 100 people, mostly young, showed signs of abnormal behavior after taking the drug.
Earlier this year, Japan broadened its probe of Tamiflu to look at flu drugs Relenza and amantadine, after reports of abnormal behavior among young patients.
FDA staff reviewed recent side effect reports on amantadine and rimantadine, another flu drug in amantadine's class, but recommended no label changes. Amantadine already has a strong warning about suicide attempts and an increase in seizures seen in patients on the drug, while rimantadine notes seizure-like activity and hallucinations.
Tamiflu was having lackluster sales as a drug to prevent and treat seasonal flu but got a second life when it was the first drug to show real efficacy in treating and preventing bird flu.