title: Safety and pharmacokinetics of intravenous zanamivir treatment in hospitalized adults with influenza: an open-label, multicenter, single-arm, phase II study.
abstract: BACKGROUND
  Intravenous zanamivir is a neuraminidase inhibitor suitable for treatment of hospitalized patients with severe influenza.
  
  
  METHODS
  Patients were treated with intravenous zanamivir 600 mg twice daily, adjusted for renal impairment, for up to 10 days. Primary outcomes included adverse events (AEs), and clinical/laboratory parameters. Pharmacokinetics, viral load, and disease course were also assessed.
  
  
  RESULTS
  One hundred thirty patients received intravenous zanamivir (median, 5 days; range, 1-11) a median of 4.5 days (range, 1-7) after onset of influenza; 83% required intensive care. The most common influenza type/subtype was A/H1N1pdm09 (71%). AEs and serious AEs were reported in 85% and 34% of patients, respectively; serious AEs included bacterial pulmonary infections (8%), respiratory failure (7%), sepsis or septic shock (5%), and cardiogenic shock (5%). No drug-related trends in safety parameters were identified. Protocol-defined liver events were observed in 13% of patients. The 14- and 28-day all-cause mortality rates were 13% and 17%. No fatalities were considered zanamivir related. Pharmacokinetic data showed dose adjustments for renal impairment yielded similar zanamivir exposures. Ninety-three patients, positive at baseline for influenza by quantitative polymerase chain reaction, showed a median decrease in viral load of 1.42 log10 copies/mL after 2 days of treatment.
  
  
  CONCLUSIONS
  Safety, pharmacokinetic and clinical outcome data support further investigation of intravenous zanamivir.
  
  
  BACKGROUND
  NCT01014988.
authors: Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts.
authors: Francisco M
authors: FM
authors: Marty
authors: Choy Y
authors: CY
authors: Man
authors: Charles
authors: C
authors: van der Horst
authors: Bruno
authors: B
authors: Francois
authors: Denis
authors: D
authors: Garot
authors: Rafael
authors: R
authors: Mánez
authors: Visanu
authors: V
authors: Thamlikitkul
authors: José A
authors: JA
authors: Lorente
authors: Francisco
authors: F
authors: Alvarez-Lerma
authors: David
authors: D
authors: Brealey
authors: Henry H
authors: HH
authors: Zhao
authors: Steve
authors: S
authors: Weller
authors: Phillip J
authors: PJ
authors: Yates
authors: Amanda F
authors: AF
authors: Peppercorn
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D005260:Female; D006760:Hospitalization; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000302:isolation & purification; D007251:Influenza, Human / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D019562:Viral Load; D053243:Zanamivir / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*
chemical_list: D000998:Antiviral Agents; D053243:Zanamivir
keywords: A/H1N1pdm09; Influenza; hospitalized; intravenous zanamivir; pandemic influenza; safety; zanamivir
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