Intravenous Zanamivir in Hospitalized Patients With Influenza

Pediatrics. 2017 Nov;140(5):e20162727. doi: 10.1542/peds.2016-2727.

Abstract

Background: Children with severe influenza infection may require parenteral therapy if oral or inhaled therapies are ineffective or cannot be administered. Results from a study investigating intravenous (IV) zanamivir for the treatment of hospitalized infants and children with influenza are presented.

Methods: This phase II, open-label, multicenter, single-arm study assessed the safety of investigational IV zanamivir in hospitalized children with influenza. Safety outcomes included treatment-emergent adverse events (TEAEs), clinical laboratory measurements, and vital signs. Clinical outcomes, pharmacokinetics, and virologic efficacy data were collected as key secondary outcomes.

Results: In total, 71 children received treatment with investigational IV zanamivir (exposure comparable to 600 mg twice daily in adults). TEAEs and serious TEAEs (STEAEs) were reported in 51 (72%) and 15 (21%) patients, respectively. The mortality rate was 7%, and median durations of hospital and ICU stays were 6 and 7.5 days, respectively. No STEAEs or deaths were considered related to IV zanamivir treatment, and no patterns of TEAEs, laboratory abnormalities, or vital signs were observed. The mean zanamivir exposures from 34 patients with normal renal function who received 12 mg/kg, 14 mg/kg, or 600 mg of IV zanamivir ranged from 64.5 to 110 hour·µg/mL. The median change from baseline in the viral load was -1.81 log10 copies per mL after 2 days of treatment.

Conclusions: The safety profile of IV zanamivir was favorable, with no drug-related STEAEs reported. The majority of children experienced virologic response and clinical improvement during the treatment course. Systemic zanamivir exposures in children were consistent with adults.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adolescent
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Child
  • Child, Preschool
  • Female
  • Hospitalization / trends*
  • Humans
  • Infant
  • Influenza, Human / diagnosis*
  • Influenza, Human / drug therapy*
  • Influenza, Human / epidemiology
  • Infusions, Intravenous
  • Male
  • Neutropenia / chemically induced
  • Viral Load / drug effects
  • Viral Load / physiology
  • Zanamivir / administration & dosage*
  • Zanamivir / adverse effects

Substances

  • Antiviral Agents
  • Zanamivir