U.S. regulators are studying the deaths of 12 children in Japan who
took Roche AG's flu-fighting drug Tamiflu, officials said on Thursday, but they
said it was difficult to tell whether the drug played a role in any of the cases.
The U.S. Food and Drug Administration said it was "concerning" that
32 psychiatric events, such as hallucinations and abnormal behavior, also had
been reported in children who took Tamiflu, which is in high demand because
it is considered to be one of the best defenses against avian flu in people.
All but one of the psychiatric problems also were reported in Japan, the FDA
The agency will ask for input on the cases from an advisory panel of outside
experts at a public meeting on Friday. Officials said the review was part of
the routine monitoring of the safety of medicines used by children.
In a separate summary posted on the FDA Web site, Roche said: "There is
no increase in deaths and neuropsychiatric events in patients on Tamiflu versus
influenza patients in general."
Roche shares fell 2.7 percent in Swiss trading. Shares of Gilead Sciences Inc.,
which invented the drug and receives royalties on Tamiflu sales, were down 1.6
percent in afternoon Nasdaq trade.
Interest in Tamiflu has risen as experts around the world warn of the possibility
for an H5N1 bird flu pandemic in people. Several countries are stockpiling Tamiflu,
which may be able to lessen symptoms.
Earlier this week Roche reported two possible suicides of Japanese youth who
took Tamiflu but said there was no clear evidence the drug contributed.
"Tamiflu is recognized as causing psychological disturbance, and therefore
the apparent suicidal behavior of these two teenagers has been linked to taking
Tamiflu," analysts at Morgan Stanley Equity Research said in a statement.
The FDA said the 12 deaths it was reviewing included one suicide, four cases
of sudden death and four cases of cardiac arrest. There also were single cases
of pneumonia, asphyxiation and acute pancreatitis.
"The level of detail in these reports was highly variable and determining
the contribution of Tamiflu to the deaths was difficult," the FDA summary
"At this point in time, we cannot make an association between Tamiflu
and the deaths of these children," said Dr. Murray Lumpkin, FDA deputy
commissioner for international and special programs. He said no similar cases
have been seen in the United States.
"But we thought it was very important to talk about these publicly with
our advisory committee," Lumpkin said.
The "most alarming" psychiatric events included two cases in which
a 12-year-old and a 13-year-old jumped out of the second-floor windows of their
homes after receiving two doses of Tamiflu, the FDA summary said.
Warnings about possible skin reactions may need to updated on the Tamiflu label,
the FDA said. Twelve cases have been reported, including one of a severe skin
problem known as Steven-Johnsons syndrome that was reported in a 3-year-old.
The agency said it had requested more information from Roche and Japanese regulatory
authorities and had received preliminary responses.
"We ... conclude that there is virtually no chance of the FDA making any
significant changes to the labeling of Tamiflu as a result of these observations,"
the Morgan Stanley team said.
Roche will present data from three drug databases and a study of Tamiflu use
in young children at the advisory panel meeting, company spokesman Al Wasilewski
"Over the past six years, Tamiflu has been used widely and has set a consistent
safety record in both the United States and Japan," he said.