IV Zanamivir Addresses 'Critical Unmet Need' for Hospitalized Children with Severe Flu
NEW ORLEANS, LA—For children hospitalized with severe flu, intravenous (IV) zanamivir may be the answer for those at high risk of complications who cannot tolerate enteral therapy, a study presented at IDWeek has found.
Citing “a critical unmet need” for an effective parenteral anti-influenza for this population, Jeffrey Blumer, MD, PhD, Department of Pediatrics, University of Toledo, Toledo, OH, and colleagues examined the safety, tolerability, and pharmacokinetics (PK) of IV zanamivir in 71 patients from 5 countries.
Zanamivir is a neuraminidase inhibitor in development for treatment of hospitalized patients with severe flu.
The investigators selected doses that would provide comparable exposures to 600mg in adults. Hospitalized, symptomatic children with laboratory-confirmed flu who presented within 7 days of onset of illness were treated with IV zanamivir twice daily for 5–10 days at 14mg/kg if 0.5–<6 years of age, or 12mg/kg (max 600mg) if 6–<18 years, with doses adjusted for renal function. Median time from onset of flu symptoms to IV zanamivir was 4 days (range, 0–7 days).
Median patient age was 7 years (range, 0.6–17 years). A total of 69% had received prior oseltamivir (median, 2 days), and 56% had chronic medical conditions. At baseline, 59% of the patients had an infiltrate on chest X-ray; 34% required mechanical ventilation; and 6%, extracorporeal membrane oxygenation. During the study, 65% required treatment in the intensive care unit. The 14-day cumulative mortality was 4% and the 28-day cumulative mortality, 7%.
“Safety, PK, clinical outcomes, and virology were assessed for up to 23 days post-treatment,” Dr Blumer reported.
Mean serum zanamivir AUCs from 34 patients with normal renal function who received 12mg/kg, 14mg/kg, or 600mg of the agent ranged from 64.5–110 h*mg/mL, generally consistent with that seen in adults, 82.9–90.3 h*mg/mL, they reported.
Among the 71 patients, influenza subtypes were A/untyped, A/N1N1 pdm09, A/H3N2, B, B + A/H3N2 and unknown. For the 77% of patients who were PCR-positive for flu at baseline, the change in viral load was similar for all subtypes from baseline (Day 1) to Day 5.
“A treatment emergent resistance substitution, E119G, was detected in a Day 5 H1N1 isolate from an immunocompetent patient who improved clinically while on IV zanamivir,” Dr. Blumer noted. “No phenotype data were available, as the sample could not be cultured.”
A total of 72% of patients experienced adverse events (AEs) and 21% had serious AEs, including 5 deaths; however, no serious AEs were identified by the investigator to be drug-related and no pattern of AEs or serious AEs attributable to IV zanamivir were identified. No clinically significant findings were observed in laboratory tests, vital signs, or ECGs.
“Dose selection based on age, weight, and renal function provided exposure similar to adults, confirming an appropriate pediatric dosing regimen,” the investigators concluded.