title: Pharmacokinetics and safety of intravenous oseltamivir in infants and children in open-label studies.
abstract: OBJECTIVE
  Critically ill children with influenza may be unable to swallow or absorb oral drugs. An intravenous (IV) formulation of the antiviral oseltamivir was evaluated in two prospective open-label studies.
  
  
  METHODS
  Hospitalized children aged <1 year (NCT01053663) or 1-12 years (NCT01033734) with clinical or laboratory-confirmed influenza, normal renal function, and who are unable to tolerate and/or absorb oral medication were enrolled. Patients received oseltamivir 2-3 mg/kg (age<1 year) or 2.5-3 mg/kg (max. 100 mg; age 1-12 years) by slow IV infusion twice daily for up to 6 days. Blood samples were taken for pharmacokinetics and nasal swabs taken to monitor viral shedding and resistance (by reverse transcriptase polymerase chain reaction (RTPCR) and culture). Adverse events (AEs) were monitored for 30 days from treatment initiation.
  
  
  RESULTS
  17 children were enrolled (9 aged<1 year; 8 aged 1-12 years). On day 1, 11 patients had laboratory-confirmed influenza. Seven patients switched from IV to oral dosing before the 10th dose. Individual plasma oseltamivir carboxylate exposures (AUClast) ranged from 1,700 to 11,500 h x ng/mL. 23 AEs were reported in 10 patients; 2 were considered treatment-related (rash, infusion site erythema). Eight serious AEs (SAEs) were reported in 7 patients, including 3 deaths in patients aged <1 year; none were considered treatment-related. Two SAEs caused treatment withdrawal. Six patients had influenza detected on or after day 11 of treatment. The oseltamivir resistance mutation H275Y was detected in three samples from 1 patient with H1N1pdm09 infection.
  
  
  CONCLUSIONS
  IV oseltamivir was well tolerated in this sample of seriously ill children. The small patient numbers precluded any formal analysis by age group or dose.
authors.forename: Flor M
authors.initials: FM
authors.lastname: Muñoz
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Anderson
authors.forename: Jaime G
authors.initials: JG
authors.lastname: Deville
authors.forename: Barry
authors.initials: B
authors.lastname: Clinch
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Kamal
mesh_terms: D000367:Age Factors; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005260:Female; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007251:Influenza, Human / Q000175:diagnosis / Q000188:drug therapy*; D007262:Infusions, Intravenous; D008297:Male; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D053139:Oseltamivir / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D061214:Patient Safety; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D014481:United States; D019562:Viral Load; D017201:Virus Shedding
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir