Bird Flu: Science and Policy

[Biowatch]

Monitor Children on Flu Drug, F.D.A. Urges

[Apparently Tamiflu use is much higher in Japan than elsewhere, so adverse events would show up there sooner.]
http://www.nytimes.com/2006/11/14/health/policy/14tamiflu.html?_r=1&oref=slogin

By THE ASSOCIATED PRESS
Published: November 14, 2006

WASHINGTON, Nov. 13 (AP) — Doctors and parents should watch for signs of bizarre behavior in children treated with the flu drug Tamiflu, federal health officials suggested on Monday in citing an increasing number of such cases from overseas.

Food and Drug Administration officials do not know whether 103 cases recently reported, including three deaths from falls, are linked to the drug or to the flu virus, or to a combination. Most of the cases involved children.

Still, F.D.A. staff members suggested updating the Tamiflu label to recommend that all patients, especially children, be closely monitored while using the drug. They also acknowledged that stopping treatment with Tamiflu could harm influenza patients if the virus were the cause of delirium, hallucinations and other abnormal behavior like aggression and suicidal thoughts.

The pediatric advisory committee of the drug agency is to discuss the recommendation on Thursday. The agency is not required to follow the advice of its outside panels but usually does. A spokeswoman for the agency did not immediately return a call for comment.

A year ago, the same panel rejected linking Tamiflu to reports of 12 deaths in Japanese children since 2000 and voted against changing the drug label to suggest such a concern. At that time, however, the committee recommended that the drug agency continue to monitor the drug’s safety and return a year later with an update.

The panel decision after reviewing the update is likely to be closely watched because Tamiflu could have an important role in an outbreak of avian flu. The drug does not prevent flu but can reduce the length and severity of its symptoms.

Most of the 103 recent cases of bizarre behavior are from Japan, where the number of Tamiflu prescriptions is about 10 times that in the United States, with more than twice the population. The cases occurred from Aug. 29, 2005, to July 6, 2006.

The Japanese Tamiflu label now warns that disturbances in consciousness, abnormal behavior, delirium, hallucinations, delusions and convulsions may occur. It also recommends patients be carefully monitored and the drug be stopped if any abnormality is observed.

Even though severe flu cases of the flu can set off those conditions, the number and nature of the cases — along with comments from doctors who believed that the abnormal behavior was associated with the drug — have kept the drug agency from ruling out Tamiflu as the cause, according to agency documents.

The agency staff called the proposed changes prudent, because American use of Tamiflu could jump to Japan’s levels. The current American label mentions only “seizure and confusion” seen in some patients.

Tamiflu is made by the Swiss pharmaceutical company Roche Holding. A spokesman for Roche did not immediately return messages for comment. Previously, Roche has cited studies from the United States and Canada that show the death rate of influenza patients who took Tamiflu to be far below those who did not.
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FDA Urges Caution on Flu Drug
By PATRICIA KOWSMANN
November 14, 2006; Page B2

WASHINGTON -- Food and Drug Administration staff recommended that the label for Roche Holding AG's flu drug Tamiflu be updated to include a precaution related to possible psychiatric problems in patients who take it.

The move follows a 10-month review that found 103 cases of "neuropsychiatric adverse events," including the death of a 14-year-old boy who fell after climbing on a balcony railing.

Of the cases, 67% were in children and 95% occurred outside the U.S., mostly in Japan, Tamiflu's biggest consumer. Two other related deaths by people who took Tamiflu were reported, including an adult who left a suicide note.

The officials still don't know if the new cases, reported from August 2005 to July, are linked to the drug, to the flu virus, or a combination of the two.

In Japan, Tamiflu's label already carries information on such events.

"Roche continuously reviews post-marketing safety information, and as a result, has agreed with the FDA that the Tamiflu label be revised to include reports of neuropsychiatric events such as self-injury and delirium in patients with influenza," a Roche statement said.

Write to Patricia Kowsmann at [e-mail]
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