Relenza use cautions by GlaxoSmithKline and FDA

By Eileen McGaurin

The death of a pregnant women who received improper dosage of the antiviral drug Relenza has prompted the FDA and GlaxoSmithKline to issue warnings to health care professionals regarding its use.

Relenza, a powdery inhalant by GSK, was voted against by the FDA's own drug advisory committee and was linked to 22 deaths before its approval, according to a Pulitzer Prize-winning Los Angeles Times article.

In the recent incident, GSK issued a letter to health care professionals saying the powdery drug was misused in treatment of the woman who died.

The drug was taken out of the package, "dissolved in various solutions" and then converted into a fine mist, a process called nebulization. Then it was used in a mechanical ventilator, said officials, and given to the pregnant woman over a course of three days.

"Relenza (zanamivir) Inhalation Powder is not intended to be reconstituted in any liquid formulation and is not recommended for use in any nebulizer or mechanical ventilator," read the GSK statement. "The safety, effectiveness, and stability of zanamivir use by nebulization have not been established."

The death of the woman, which occurred outside the U.S., was attributed to obstruction of the ventilator due to the stickiness of the lactose in the drug, according to the FDA.

The FDA approved Relenza in July of 1999 despite a negative recommendation from its own Anti-viral Drugs Advisory Committee, according to David Willman of the L.A. Times, Pulitzer winner in 2001 for a series of articles about prescription drugs and the FDA.

The committee was so "underwhelmed" by the drug's performance, wrote Willman, that they voted 13 to 4 to reject it. FDA committee members found that Relenza was "no more effective than a placebo in treating common flu symptoms" and that it would "reduce by about one day a patients symptoms."

In July of 2000, one year after its approval, GSK issued revised safety labeling for Relenza to more clearly reflect the serious respiratory adverse events, a concern that was voiced earlier voiced by an FDA director.

In April of 2008, GSK issued new warnings about Relenza when instances of "delirium and abnormal behavior leading to injury" were reported, mostly from Japan.

"These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution," stated the GSK letter. "The contribution of Relenza to these events has not been established."

Relenza is recommended for use by pregnant women who have the flu, although it is classified as "Pregnancy Category C," meaning it has not been studied in pregnant women, according to the CDC.

"The CDC has looked at these issues carefully for pregnant women: because the risks of influenza for pregnant women are serious, CDC believes that the benefits of antiviral therapy outweigh the potential for risks from the drugs."

The CDC added that antiviral drugs are most beneficial if treatment starts within 2 days of the start of flu symptoms and that antiviral therapy does not substitute for vaccination against seasonal and or H1N1 influenza.