FDA Panel Urges Stronger Warnings on Flu Drugs


GAITHERSBURG, Md., Nov. 28 -- Labeling for two major flu drugs, oseltamivir (Tamiflu) and zanamivir (Relenza), should be strengthened, an FDA panel has recommended.
In an eight-to-six vote, panel members agreed that package inserts do not adequately address safety concerns surrounding neuropsychiatric events, including delirium and self-injury, that have been associated with the medications.
New language should note that deaths have occurred as a result of those events and may note that flu itself may cause such events, although it remains unclear if the drugs contribute to them, the panel said.
Other recommendations by the panel include explanation that such neuropsychiatric events are rare, occur abruptly, and may result in death, and that patients taking either drug should be monitored closely.
The makers of the drugs -- Roche for oseltamivir and GlaxoSmithKline for zanamivir -- argued that the existing language was adequate.
In its own analysis of more than 150,000 patients, Roche experts argued that the drug is not the cause of the neuropsychiatric events.
"The data increasingly points to the role of influenza in these events," Roche product director David Reddy said. He noted that the disease can cause high fevers, which are associated with "delirium and hallucination."
Nevertheless, the company said it would abide by the FDA's ruling. The agency usually follows the advice of its expert panels, but is not obliged to do so.
The two drugs both aim at blocking the viral enzyme neuraminidase, but they are administered differently. Oseltamivir is available both as an oral capsule and as a suspension, while zanamivir is a dry powder administered in an inhaler.
Neuropsychiatric events have been associated with both drugs, but the majority of cases -- including some deaths -- have been linked to oseltamivir and most of those have taken place in Japan, the FDA said.
The FDA's adverse event reporting system found 596 neuropsychiatric events since oseltamivir was approved, including 16 deaths associated with such an event, according to briefing documents presented to the panel.
The neuropsychiatric events generally had a median onset of 24 hours and resolved quickly in a median of six hours, the agency found.
Zanamivir was associated with 115 events -- 74 of them among patients 21 or younger -- but no deaths, the agency said.
The panel agreed that labeling for two other flu drugs -- the M2 inhibitors amantadine hydrochloride (Symmetrel) and rimantadine hydrochloride (Flumadine) -- does not need to be changed.