Fatal respiratory events caused by zanamivir nebulization.

To the Editor—GlaxoSmithKline was very concerned to learn of the fatality of a 25-year-old pregnant woman with severe H1N1 influenza A following nebulized administration by means of mechanical ventilation of zanamivir solution, described in the letter by Kiatboonsri et al [1]. This solution had been made by the treating hospital pharmacy from the lactose powder formulation of zanamivir, marketed as Relenza Diskhaler. As highlighted in GlaxoSmithKline’s communication to health care professionals, this formulation is not intended to be reconstituted in any liquid formulation for administration by nebulization and is not approved for this use [2]. GlaxoSmithKline wishes to distinguish between the lactose powder solution administered to the patient described in the letter [1] and the aqueous saline solution of zanamivir that was used in early studies of nebulized zanamivir and that is currently in clinical development for intravenous administration in patients with severe influenza. The aqueous saline solution of zanamivir does not contain lactose, the presumed cause of ventilator occlusion in this case. The safety and effectiveness of zanamivir aqueous saline solution have not yet been established, and this formulation has not been approved by the US Food and Drug Administration or any other regulatory agency. Limited safety data have not identified safety concerns when this formulation has been administered by means of nebulization to healthy volunteers and subjects hospitalized with influenza, some of whom have received zanamivir aqueous solution by means of nebulization through the global compassionate use program [3, 4]. The company has no information about the administration of nebulized zanamivir aqueous saline solution administered to patients who are undergoing mechanical ventilation. GlaxoSmithKline strongly discourages nebulization of the lactose powder formulation, which is intended only for oral inhalation by means of Diskhaler as packaged, in accordance with approved product labeling.