To date, influenza treatments have consisted only of oral (oseltamivir) or topical (zanamivir) neuraminidase inhibitor formulations, but an intravenous option is also being investigated —the selective neuraminidase inhibitor peramivir. This sialic acid analogue is characterized by a strong affinity for influenza neuraminidase and a low off rate. Researchers recently reported the results of a manufacturer-sponsored, phase II, randomized controlled trial investigating the effect of a single dose of intravenous peramivir on the course of community-acquired influenza in previously healthy individuals during the 2007–2008 influenza season in Japan.

Within 48 hours after onset of typical influenza symptoms, 99 study participants received a 300-mg dose of peramivir, 97 received a 600-mg dose, and 100 received placebo. The clinical effectiveness of peramivir became evident within the first 24 hours after treatment initiation, and, by 36 hours, both the 300-mg and the 600-mg dose groups had significantly higher proportions of afebrile patients than the placebo group. Both peramivir groups also had a significantly shorter time to resumption of usual activities (median duration, 126 hours in the 300-mg group, 127 hours in the 600-mg group, and 169 hours in the placebo group) and to reduction of viral shedding; the three groups had similar viral titers at baseline, but by day 3, the proportion of virus-positive patients was significantly lower in the 300-mg group (37%) and the 600-mg group (26%) than in the placebo group (52%). Tolerability of peramivir was excellent.

Comment: Peramivir appears to be a promising new antiviral in the armamentarium against influenza and has already received FDA emergency-use authorization for the treatment of severe pandemic H1N1 influenza. Its intravenous formulation makes it particularly attractive for treating severely ill patients, but dose-finding trials have not yet been completed in this population. Animal studies indicate that multiple doses of peramivir for up to 15 days might be appropriate for such patients.

— Thomas Glück, MD

Published in Journal Watch Infectious Diseases December 1, 2010