Intravenous Zanamivir: Experience with 200 Patients
By Amesh A. Adalja, MD, FACP, October 26, 2012
The 2009 H1N1 influenza pandemic and the resulting demand for antivirals exposed a serious gap in the current armamentarium: the lack of intravenous (IV) formulations. All FDA-approved medications for influenza at the time of the pandemic were either oral or inhalational formulations. To mitigate the potential deleterious consequences of suboptimal oral bioavailability or cumbersome inhalational devices, the FDA issued an emergency use authorization (EUA) for IV peramivir and made IV zanamivir available as an emergency investigational new drug (EIND). A team from the FDA and CDC recently published details of the clinical experience with 200 patients who were administered IV zanamivir during the period of April 2009 to April 2011.
The data was culled from an FDA database of information acquired from clinicians who have requested IV zanamivir through an EIND application and then submitted information back to the FDA once the drug was dispensed.
Important characteristics of the 200 patients whose data was analyzed include the following:
- Median age of patients was 47 years, with a range of 6 months to 91 years.
- Pregnancy was noted in 7% of recipients.
- Comorbid conditions were noted for approximately 50% of patients.
- Pneumonia was reported in 36.5%, renal failure in 25%, and shock in 12.5%.
- The majority of requests (88%) were for treatment of patients with influenza A (predominantly 2009 H1N1); 12% were for treatment of patients with influenza B.
Most patients (67%) were receiving mechanical ventilation, with 13.5% receiving extracorporeal membrane oxygenation (ECMO) and 8% on high-frequency oscillating ventilation (HFOV).
Prior to the EIND request, 78.5% of patients had been administered antiviral therapy. The breakdown listed below encompasses all antiviral agents known to be active against influenza:
- Oseltamivir: 76%
- Peramivir 10%
- Zanamivir: 4%
- Ribavirin: 1.5%
- Amantadine: 1.5%
- Rimantadine: 1.5%
The majority of treating clinicians (76.5%) did not report outcome data, so no conclusions can be drawn regarding efficacy.
Prioritize Approval of IV Antivirals
Given that IV peramivir was available during the pandemic via EUA, the demand for IV zanamivir was likely reduced. However, one clinical scenario in which IV zanamivir would be preferred is in the case of oseltamivir resistance, as cross-resistance to peramivir would be expected. Of the 200 requests for intravenous zanamivir, 25% were for confirmed or suspected oseltamivir resistance. This is a phenomenon that became near universal in the seasonal H1N1 viruses that preceded the pandemic virus and suggests that IV zanamivir should become a standard component of the antiviral armamentarium.
The other gap filled by IV formulations is that of assured bioavailability. During critical illness, IV antiviral formulations are essential for patients who cannot take oral antivirals due to gut hypoperfusion. They are also needed because inhalational zanamivir cannot be safely administered via ventilator circuit.
Given the clear need for IV formulations, further development and FDA approval of IV antivirals (zanamivir, peramivir, and oseltamivir) should be priorities.
Chan-Tack KM, Gao A, Himaya AC, et al. Clinical experience with intravenous zanamivir under an emergency IND program in the United States. J Infect Dis 2012. http://jid.oxfordjournals.org/content/early/2012/10/22/infdis.jis637.short?rss=1. Accessed October 24, 2012.