From Our 2007 Archives

FDA Panel Backs Tougher Warning on Asthma Drugs for Kids

By Steven Reinberg
HealthDay Reporter

TUESDAY, Nov. 27 (HealthDay News) -- A U.S. Food and Drug Administration advisory panel on Wednesday urged that stronger label warnings focused on children be added to the packaging for Serevent and Advair, two widely used asthma drugs.

Both drugs are long-acting beta agonist medications containing salmeterol, and are used as asthma prevention in children and adults age 4 and up.

But last year -- after a 2005 panel investigation focused mainly on the drugs' use by adults -- the FDA added a strong "black box" warning on both medications that they "may increase the risk of asthma-related death."

The FDA's Pediatric Advisory Committee's new recommendation is that this warning be extended specifically to pediatric users of the two drugs, according to Marketwatch, and that it include mention of the fact that the drugs could boost the risk of asthma-linked hospitalizations.

Both drugs are made by GlaxoSmithKline, which said it believed the current black-box warning was sufficient, according to Marketwatch. The FDA says it also plans a new safety review of the two drugs.

Marsha Rappley, chair of the panel, called the recommended label change "an urgent public health issue," according to the Wall Street Journal.

"You need to move forward soon," she told the agency.

The announcement came after the same panel recommended on Tuesday that the prescription flu drug Tamiflu (oseltamivir) should have a stronger warning label to reflect reports of bizarre behaviors and deaths among children who use the medication.

On Wednesday, the drug's manufacturer, Roche, accepted the recommendation, the Associated Press reported.

The panel, in a 9-5 vote, said Roche should change the drug's prescribing information because it doesn't adequately explain side effects reported by hundreds of patients in Japan and 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 the language should state that several patients died as a result of these behaviors, AP reported.

A spokeswoman for Roche said Wednesday that all flu patients, not just those taking Tamiflu, should be warned that the illness posed a risk of psychiatric problems. She stressed there was no causal relationship between Tamiflu and the reported cases of delirium and hallucinations, AP reported.

In addition, the FDA panel recommended that labeling for the flu drug Relenza, (zanamivir), should also reflect reports of abnormal behavior, according to Bloomberg.

The FDA is not obliged to follow its expert panels' recommendation, but it usually does. A safety review released Friday by the FDA's Division of Antiviral Products urged stronger label warnings for both flu drugs, including stricter monitoring of children taking these drugs.

According to the FDA safety review, there have been 596 reported cases of psychiatric behavior associated with Tamiflu use. Most of these cases happened among patients aged 21 or younger. The majority (75 percent) occurred in Japan.

Fifty-nine of the cases were classified as delirium with impulsive behavior and self-injury. Delirium, delusions, hallucinations or psychosis accounted for another 225 cases. In total, five children died "as a result of falls from windows or balconies or running into traffic," the safety review found, and three adults committed suicide. So far, there haven't been any such cases reported in the United States, according to the FDA.

The FDA safety review also reported that in cases involving Relenza, mostly in Japan, there have been 115 reports of "delirium with impulsive behavior and self-injury in which the patient expressed 'fear' and attempted to flee or expressed a desire to 'jump,'" the agency said. There were no deaths associated with Relenza.

During its meeting on Tuesday, the advisory panel said it was unclear whether the psychiatric problems are a side effect of Tamiflu or the flu itself, AP reported.

At the hearing, representatives of Roche told the panelists that the flu itself, not Tamiflu, caused the bizarre behaviors.

"We feel that the current U.S. prescribing information is an accurate assessment of the current data," Jonathan Solsky, Roche's director of drug safety risk management, testified, according to Bloomberg.

In a statement released after the meeting, Roche reiterated its faith in the drug. "According to data analyzed from two U.S. claims databases of more than 150,000 patients, there is no increased risk for neuropsychiatric events in influenza patients treated with Tamiflu compared to untreated influenza patients," the statement said.

GlaxoSmithKline, the maker of Relenza, also released a statement after the meeting. "GSK was pleased to have the opportunity to present safety information on Relenza to the Pediatric Advisory Committee showing no conclusive evidence of a causal association between Relenza and neuropsychiatric events," the statement said.

"We believe the current Relenza U.S. prescribing information accurately reflects the safety profile of the drug," the company added.

The FDA first began reviewing Tamiflu in 2005. Since November 2006, the drug's label has had a warning focused on self-injury and delirium, advising that patients be monitored during treatment. In March, the Japanese Ministry of Health, Labor and Welfare limited Tamiflu use in patients aged 10 to 19 years old.

Tamiflu is approved both as a preventative and a treatment for flu for adults and children aged 1 year and older.

Relenza is approved as both a flu preventative and a treatment in adults and children aged 5 years old and older.

SOURCES: Pediatric Safety Update for Tamiflu, Division of Antiviral Products, U.S. Food and Drug Administration; Nov. 27, 2007, statements, GlaxoSmithKline and Roche; Bloomberg news; Associated Press, MarketWatch

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