Neuropsychiatric Symptoms, Deaths Prompt Labeling Changes for Relenza

By Charles Bankhead
PHILADELPHIA, April 2 -- Reports of neurologic symptoms and abnormal behavior, including some deaths, in patients using neuraminidase inhibitors, prompted an update of the package insert for zanamivir (Relenza), GlaxoSmithKline announced in a letter to healthcare professionals.
The postmarketing reports, primarily from Japan, cited symptoms that included seizures, hallucinations, delirium, and abnormal behavior, GSK medical director Judith Ng-Cashin, M.D., said in the letter.
In November, an FDA panel recommended labeling changes for zanamivir and oseltamivir (Tamiflu), saying that package inserts did not adequately address safety concerns surrounding the neuropsychiatric events (See: FDA Panel Urges Stronger Warnings on Flu Drugs).
The new language should note that deaths have occurred as a result of those events, the panel said, and could note that the flu itself may cause such events and that it remains unclear if the drugs contribute to them.
The new Warnings and Precautions section of the zanamivir package insert now includes a subsection called "Neuropsychiatric Events," providing that information and guidance to clinicians.
The new subsection includes the following:
Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made, but they appear to be uncommon based on usage data for Relenza. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of Relenza to these events has not been established.
The company also added cautionary information about neurologic and behavioral symptoms to the side effects section of the patient information for Relenza.
In November, the FDA's adverse event reporting system found 115 events associated with zanamivir, 74 of them among patients 21 or younger, but no deaths.