FDA Panel Backs Tougher Warning for Tamiflu

FDA Panel Backs Tougher Warning for Tamiflu
A close up of Roche AG's Tamiflu pills, known generically as oseltamivir, are seen at the Center for Disease Control in Bangkok October 21, 2005. The safety of influenza drugs is under scrutiny as advisers to the U.S. Food and Drug Administration on Tuesday analyzed abnormal psychiatric behavior seen in some patients, especially children. Medical experts are reviewing cases of patients taking Roche Holding AG's (Adrees Latif/Reuters)TUESDAY, Nov. 27 (HealthDay News) -- A U.S. Food and DrugAdministration advisory panel recommended Tuesday that the prescriptionflu drug Tamiflu (oseltamivir) should have a stronger warning label toreflect reports of bizarre behaviors and deaths among children who use themedication.
On Wednesday, the drug's manufacturer, Roche, accepted therecommendation, the Associated Press reported.
The FDA's Pediatric Advisory Committee, in a 9-5 vote, said Rocheshould change the drug's prescribing information because it doesn'tadequately explain side effects reported by hundreds of patients in Japanand the United States, according to Bloomberg News.
The drug's label mentions reports of delirium and self-injury,primarily among children in Japan, but the advisory panel said thelanguage should state that several patients died as a result of thesebehaviors, AP reported.
A spokeswoman for Roche said Wednesday that all flu patients, not justthose taking Tamiflu, should be warned that the illness posed a risk ofpsychiatric problems. She stressed there was no causal relationshipbetween Tamiflu and the reported cases of delirium and hallucinations,AP reported.
In addition, the FDA panel recommended that labeling for the flu drugRelenza, (zanamivir), should also reflect reports of abnormal behavior,according to Bloomberg.
The FDA is not obliged to follow its expert panels' recommendation, butit usually does. A safety review released Friday by the FDA's Division ofAntiviral Products urged stronger label warnings for both drugs, includingstricter monitoring of children taking these drugs.
According to the FDA safety review, there have been 596 reported casesof psychiatric behavior associated with Tamiflu use. Most of these caseshappened among patients aged 21 or younger. The majority (75 percent)occurred in Japan.
Fifty-nine of the cases were classified as delirium with impulsivebehavior and self-injury. Delirium, delusions, hallucinations or psychosisaccounted for another 225 cases. In total, five children died "as a resultof falls from windows or balconies or running into traffic," the safetyreview found, and three adults committed suicide. So far, there haven'tbeen any such cases reported in the United States, according to theFDA.
The FDA safety review also reported that in cases involving Relenza,mostly in Japan, there have been 115 reports of "delirium with impulsivebehavior and self-injury in which the patient expressed 'fear' andattempted to flee or expressed a desire to 'jump,'" the agency said. Therewere no deaths associated with Relenza.
During its meeting on Tuesday, the advisory panel said it was unclearwhether the psychiatric problems are a side effect of Tamiflu or the fluitself, AP reported.
At the hearing, representatives of Roche told the panelists that theflu itself, not Tamiflu, caused the bizarre behaviors.
"We feel that the current U.S. prescribing information is an accurateassessment of the current data," Jonathan Solsky, Roche's director of drugsafety risk management, testified, according to Bloomberg.
In a statement released after the meeting, Roche reiterated its faithin the drug. "According to data analyzed from two U.S. claims databases ofmore than 150,000 patients, there is no increased risk forneuropsychiatric events in influenza patients treated with Tamiflucompared to untreated influenza patients," the statement said.
GlaxoSmithKline, the maker of Relenza, also released a statement afterthe meeting. "GSK was pleased to have the opportunity to present safetyinformation on Relenza to the Pediatric Advisory Committee showing noconclusive evidence of a causal association between Relenza andneuropsychiatric events," the statement said.
"We believe the current Relenza U.S. prescribing information accuratelyreflects the safety profile of the drug," the company added.
The FDA first began reviewing Tamiflu in 2005. Since November 2006, thedrug's label has had a warning focused on self-injury and delirium,advising that patients be monitored during treatment. In March, theJapanese Ministry of Health, Labor and Welfare limited Tamiflu use inpatients aged 10 to 19 years old.
One expert believes a new warning is appropriate for Tamiflu. "The ideathat there have been 596 neuropsychiatric events is a reason for the FDAto put a strong warning on the label," said Dr. Marc Siegel, a clinicalassociate professor of medicine at New York University School of Medicinein New York City.
But he is also concerned that the public might overreact.
"I am not a fan of replacing fear of a disease with fear of thetreatment for the disease," said Siegel, speaking before the advisorypanel met. "You don't need to go from one panic to another."
Tamiflu is overused, however, Siegel added. "It's supposed to be usedin a very narrow window, and I am not surprised that there have beenpsychiatric side effects related to this drug," he said. "Maybe the newwarning will lead to less overuse."
Tamiflu is approved both as a preventative and a treatment for flu foradults and children aged 1 year and older.
Relenza is approved as both a flu preventative and a treatment inadults and children aged 5 years old and older.
More information
For more on the flu, visit the U.S. Centers for Disease Control and Prevention.