Peramivir: Another Tool for Influenza Treatment?

During the 2009 influenza A (H1N1) (pH1N1) pandemic, young persons and groups with certain health conditions, including pregnant women, were disproportionately affected, although illnesses and influenza-related complications were seen in all age groups [1, 2]. Vaccine was not available until after the peak of the fall pH1N1 wave in the Northern Hemisphere, after the peak of pH1N1 circulation in the Southern Hemisphere, and not until early 2010 in many developing countries [3]. Thus, influenza antiviral drugs were the primary influenza-specific pharmacologic tools available to minimize severe illness and death, and there were limited treatment options for severely ill persons, especially those receiving mechanical ventilation. One year after the pandemic and as the annual influenza season looms for the Northern Hemisphere, this is a salient time to think about the tools at hand and in development to mitigate severe illness from influenza infection. Currently, 2 classes of antiviral drugs are approved by the US Food and Drug Administration (FDA) and widely available for the treatment of influenza: neuraminidase inhibitors (NAIs) and adamantanes [4, 5]. However, only NAIs are recommended for treatment of influenza A and B because of a high level of resistance to adamantanes among influenza A viruses, including pH1N1, and because adamantanes are not effective against influenza B [4, 5]. NAIs target the influenza A and B virus neuraminidase and, by inhibiting enzyme activity, prevent the release of new virions, thereby stopping virus replication. Adamantanes target the influenza A virus M2-protein and block virus replication by inhibiting H1 flow across the M2 protein channel. Since April 2009, pH1N1 viruses have been inherently resistant to adamantanes because of the presence of asparagine at amino acid 31 in the M2 protein and, except for rare instances, are susceptible to NAIs [5–7]. Although only 2 NAIs (oral oseltamivir and inhaled zanamivir) are licensed and approved for use [4, 5], 2 investigational intravenous NAIs (peramivir and zanamivir) were available in the United States by FDA emergency investigational new drug (eIND) request from the manufacturer during the pH1N1 pandemic [8,9]. Peramivir was available in the United States by Emergency Use Authorization (EUA) from 23 October 2009 through 23 June 2010 [8, 9]. In addition, intravenous peramivir has had market authorization in Japan since January 2010 and South Korea since August 2010 and is otherwise available only through clinical trials in several countries, including the United States [9]. In this issue of Clinical Infectious Diseases, Hernandez et al [9] describe a convenience sample of 31 hospitalized patients in the United States who received peramivir under eIND during the pH1N1 pandemic. There were no specified criteria for receipt of peramivir under the eIND, but most appeared to be severely ill. Among 31 patients receiving daily intravenous peramivir for a duration of 2–15 days, none were reported to have a serious adverse event. Forty percent of patients had acute renal failure and required renal replacement therapy, and the drug was effectively cleared without any adverse events. In addition, 2 pregnant women recovered from their influenza infections and delivered healthy infants without immediate adverse events noted from either oseltamivir or peramivir; long-term follow-up of these infants would be useful. One-third of patients were children, the majority of whom were 10–17 years of age; all tolerated peramivir without significant adverse events. The EUA required mandatory reporting of selected adverse events by clinicians to FDA via the FDA Adverse Event Reporting System (AERS) [8]. The FDA received AERS reports on 237 patients (19 children and 218 adults), from 1250 peramivir releases under the EUA through 12 March 2010, most of whom were critically ill and with comorbidities Received 15 November 2010; accepted 4 January 2011. Correspondence: Seema Jain, MD, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, MS A32, Atlanta, GA 30333 (bwc8@cdc.gov). Clinical Infectious Diseases 2011;52(6):707–709 Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2011. 1058-4838/2011/526-0001$37.00 DOI: 10.1093/cid/cir010