Pediatric Advisory Committee Recommends Labeling Changes for Flu Drugs

The FDA’s Pediatric Advisory Committee voted 9–5 to recommend changing the label of Roche’s flu medication Tamiflu to reflect the potential for neuropsychiatric adverse events, but it did not specify what changes should be made.

The relationship between Tamiflu (oseltamivir phosphate) and neuropsychiatric adverse events, including suicides, cannot be determined, the FDA said. Committee members proposed including an indication that the adverse events are sometimes fatal and adding language showing the uncertainty over the drug’s causal effect.

The committee also voted to change the labeling of GlaxoSmithKline’s (GSK) Relenza (zanamivir) to reflect an increase in adverse event reports but did not determine what the changes should be or whether the label should be the same as Tamiflu’s.

The meeting was the committee’s third after convening in 2005 to discuss reports of neuropsychiatric adverse events in pediatric patients in Japan who received Tamiflu. Last year, Roche revised its Tamiflu package insert to add warnings about the potential for self-injury and confusion, particularly in pediatric patients.

While it is difficult to determine a direct causal relationship between Tamiflu and the patient deaths, the drug’s contribution “cannot be completely excluded at this time,” Adrienne Rothstein, safety evaluator for the Office of Surveillance and Epidemiology (OSE), said.

Twenty-five patients younger than 21 years old have died while taking Tamiflu, with 21 of the cases occurring in Japan and three in the U.S. Five of the deaths came from children “falling from windows or balconies or running into traffic,” the FDA said.

Roche has not identified any increased risk of neuropsychiatric adverse events in patients taking Tamiflu compared with those not taking the drug, the company’s Drug Safety Risk Management Director Jonathan Solsky said. Tamiflu’s current labeling continues to reflect all available data and should not change, he added.