Clinical experience with intravenous zanamivir under an Emergency IND program in the United States (2011-2014)

Antivir Ther. 2015;20(5):561-4. doi: 10.3851/IMP2944. Epub 2015 Feb 10.

Abstract

Background: Since the emergence of 2009 H1N1 virus, intravenous (IV) zanamivir has been authorized as an investigational treatment for patients with serious and life-threatening influenza through an Emergency Investigational New Drug application (EIND). This review encompasses the FDA's EIND database from May 2011 to June 2014.

Methods: This is a retrospective descriptive review of patient clinical data in the FDA's IV zanamivir EIND database from May 2011 to June 2014.

Results: Of 364 IV zanamivir EIND requests, most (83%) patients were aged 18-64 years, 8 (2%) were pregnant, and 29 (8%) were children. 234 (64%) patients had ≥1 comorbidity reported. The majority (87%) were receiving oseltamivir when IV zanamivir was requested, and 33% had suspected (n=120; no improvement or worsening on oseltamivir) H275Y oseltamivir resistance. Influenza A was reported for 300 patients: confirmed 2009 H1N1 (n=163), suspected 2009 H1N1 (n=8), confirmed H3N2 (n=4) and not subtyped (n=125). Influenza B was reported for 25 patients. Many patients (87%) required invasive mechanical ventilation, 23 (6%) received high frequency oscillatory ventilation, and 74 (20%) received extracorporeal membrane oxygenation (ECMO). 289 (79%) patients had ≥1 complication such as renal failure (n=124; 77/124 required dialysis), bacteraemia (n=18), shock (n=95) or pneumonia (n=159). Of 134 (37%) patients with available outcome data, 83 died and 51 survived.

Conclusions: IV zanamivir EIND authorizations were for treatment of critically ill adult patients with 2009 H1N1, including a substantial number with suspected oseltamivir resistance. Data from prospective, randomized controlled trials are needed and are ongoing to assess the safety and efficacy of IV zanamivir for treatment of hospitalized patients with severe influenza.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H3N2 Subtype / drug effects
  • Influenza B virus / drug effects
  • Influenza, Human / drug therapy*
  • Investigational New Drug Application*
  • Male
  • Middle Aged
  • Oseltamivir / therapeutic use
  • Pregnancy
  • Retrospective Studies
  • United States
  • Young Adult
  • Zanamivir / administration & dosage
  • Zanamivir / adverse effects
  • Zanamivir / therapeutic use*

Substances

  • Antiviral Agents
  • Oseltamivir
  • Zanamivir