Mental side-effect warnings sought for flu drugs

WASHINGTON — Food and Drug Administration (FDA) experts are recommending new label warnings about possible dangerous psychiatric side effects of influenza drugs Tamiflu and Relenza, documents show.

The FDA documents, posted Friday on the agency's Web site, were prepared for a meeting Tuesday of the FDA's Pediatric Advisory Committee.

Studies revealed 596 cases in which patients who took Tamiflu experienced "neuropsychiatric events" such as delirium, delusions or hallucinations. The episodes sometimes led to impulsive behavior and self-injury. Tamiflu is made by Roche Holdings.

The problems tended to occur within 24 hours of first taking the drug, and the majority were in patients younger than 21, mostly in Japan, according to the documents. In five cases involving pediatric patients, the reported delirium resulted in death, and there were three reports of suicide in adults.

"In the remaining reports of delirium with impulsive behavior and self-injury, patients were attempting to flee or escape from windows or balconies and were unsuccessful in their efforts," the FDA documents say.

Tamiflu, available in pill and syrup form, can treat the symptoms of seasonal influenza. In a bird-flu pandemic, many experts think the drug could help reduce the length and severity of symptoms.

Safety concerns about Tamiflu arose two years ago after reports of 12 deaths and 32 cases of psychiatric problems in children in Japan. Labeling for Tamiflu in the United States notes that self-injury and delirium have occurred, primarily among pediatric patients.

Now FDA regulators are recommending that U.S. labeling be updated to note that "fatalities have occurred in adult and pediatric patients in Japan, the onset may be abrupt, and fatal events have occurred even while the patient was being monitored."

Regulators cautioned that no causal link has been established between the drug and the abnormal behavior, and that delirium and other problems can be complications of influenza.

Roche spokesman Terry Hurley said reports of abnormal behavior were "infrequent."

Regarding Relenza, an antiviral drug made by GlaxoSmithKline that is in the same class as Tamiflu, FDA experts said studies turned up 115 cases of psychiatric problems, including 74 cases in patients younger than 21. Seventy percent were in Japan. No potentially related deaths were reported.

Because Relenza, which is inhaled by mouth, is not easily absorbed, experts said the problems probably were related to the influenza rather than the treatment.

Nevertheless, they recommended updating Relenza's label to note that "postmarketing reports of hallucinations, delirium and abnormal behavior have been observed in patients" receiving the drug for treatment of influenza. The label does not warn of psychiatric side effects.

Glaxo spokesman Jeff McLaughlin said, "A review of clinical trial data and postmarketing reports demonstrated no evidence of a causal association between Relenza and neuropsychiatric adverse events."

William Schaffner, chairman of the Department of Preventive Medicine at Vanderbilt University School of Medicine in Nashville, Tenn., said the proposed warnings are "prudent and appropriate."