FDA panel to review Tamiflu's effect on brain

USA Today | November 28, 2007
By Anita Manning

A Food and Drug Administration panel on Tuesday will review reports of abnormal behavior and other brain effects in more than 1,800 children who had taken the flu medicine Tamiflu since its approval in 1999, including 55 in the USA.

Twenty-two of the U.S. reports were considered "serious," with symptoms such as convulsions, delirium or delusions, says Terry Hurley, spokesman for drugmaker Roche Laboratories.

None of the U.S. cases resulted in death. But in Japan, Hurley says, five deaths have been reported in children under 16 as a result of neurological or psychiatric problems. "Four were fatal falls, and one was encephalitis in a patient with leukemia," he says.

In addition, in people ages 17 to 21, there were two deaths in Japan, one a "fatal accident with abnormal behavior," Hurley says, and the second as a result of encephalopathy, a brain infection. Seven adult deaths attributed to neuropsychiatric problems also have been reported in Japan.

But Hurley says there is no evidence Tamiflu caused the episodes and notes that similar symptoms have been reported in flu patients who had not taken Tamiflu. He says clinical studies have found no increased risk for psychiatric or neurologic disturbances, and the company's evaluation of scientific data found no "potential mechanisms for Tamiflu to cause (central nervous system) effects." He says the company is doing further studies.

The possible association between Tamiflu and neuropsychiatric effects was first reported in Japan, and in March, the Japanese government issued a safety warning restricting the drug's use in adolescents.

Japan has been the major market for Tamiflu, accounting for 75% of the 48 million prescriptions written. The drug's Japanese distributor, Chugai Pharmaceutical Co., announced this month that it would cut by half the supply it had been planning to sell this winter, from 12 million to 6 million courses of treatment.

In a statement, the company says demand dropped after reports in February that "several teenage patients with influenza who were also taking Tamiflu had fallen from buildings after taking the drug."

Hurley said in an e-mail that 1,745 of the 1,808 reports of problems associated with Tamiflu are in Japan. He said 81% of all reports were "defined as non-serious."

In the USA, Hurley said, 2.85 million Tamiflu prescriptions have been written since 1999. A year ago Roche added a warning to its package insert label saying "people with the flu, particularly children, may be at an increased risk of self-injury and confusion shortly after taking Tamiflu," and their behavior should be monitored.

The anti-viral medication, stockpiled in the millions by countries around the world for use in a flu pandemic, is licensed to treat or prevent flu in patients older than 1 year.