Federal drug regulators said Friday there was insufficient evidence to tie the flu drug Tamiflu to the deaths of 12 Japanese children or to hallucinations, encephalitis and other symptoms suffered by some Japanese patients.
Food and Drug Administration staff said they don't think it's necessary to update the drug's labeling to reflect those deaths or possible adverse effects. But the staff is recommending adding information to the label about serious skin reactions to Tamiflu.
Unlike other ailments reported in patients who took Tamiflu, the skin reactions don't appear to be related to the influenza the patients were being treated for, officials said in papers prepared for a meeting Friday by an FDA advisory committee.
"Clearly, any time you get a report of a death or a serious occurrence, you want to look into it," said Dr. Murray Lumpkin, deputy commissioner of the U.S. Food and Drug Administration, said prior to the meeting.
The reports are being discussed as part of the annual pediatric safety review of Tamiflu and seven other drugs. The Japanese deaths were detailed in papers released before Friday's meeting. There are no reports of deaths in the United States or Europe associated with Tamiflu.
The FDA sought and received more information from the Swiss pharmaceutical company Roche Holding AG, which makes Tamiflu, and from health authorities in Japan, where use of Tamiflu is more common than in the United States.
The FDA has not yet issued any warnings or initiated any other action, spokeswoman Susan Bro said.
"Based on the information we have right now, we cannot say definitively there is a causal relation between the drug and the children's death," Lumpkin said.
An update by FDA staff also includes reports of 32 "neuropsychiatric events" associated with Tamiflu, all but one experienced by Japanese patients. Those cases included delirium, hallucinations, convulsions and encephalitis.
Roche said several studies in the United States and Canada had shown that the incidence of death in influenza patients who took Tamiflu was far lower than in those who did not.
The company also has supplied the FDA with two additional studies it commissioned that evaluated the safety of Tamiflu in pediatric patients.
Complicating the issue is that many of the Japanese death and adverse reaction reports list symptoms commonly associated with the flu, Lumpkin said.
"It is very difficult, when the underlying disease causes what it is being reported, to figure out: Is it the underlying disease? Is it the drug?" he said.
The popularity of Tamiflu in Japan may explain in part the number of reports from that country: Of 32 million people treated with Tamiflu since its approval in 1999, 24 million were in Japan, according to Roche.
Japan's Health Ministry warned last week that Tamiflu may induce "strange behavior" after reporting that two teenage boys died shortly after taking the medicine.
The Japanese distributor of the Roche-patented drug told health officials it could not rule out a link between Tamiflu and the deaths.
However, Roche said earlier this week that it "carefully reviewed these events and has concluded that a causal link cannot be established."
The U.S. labeling for Tamiflu lists nausea and vomiting as its most serious side effects. Its labeling in Japan includes any adverse effects that have been reported — including impaired consciousness, abnormal behavior and hallucinations — regardless of whether they can be attributed to the drug, according to Roche.
Tamiflu is one of the few drugs believed effective in treating bird flu, which health officials fear could spark a pandemic should it mutate into a form easily passed from human to human.