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 log10copies/mL after 2 days of treatment.Conclusions. Safety, pharmacokinetic and clinical outcome data support further investigation of intravenous zanamivir.Clinical Trials Registration NCT01014988. © 2013 The Author.