Oseltamivir pharmacokinetics, dosing, and resistance among children aged <2 years with influenza
David W Kimberlin1, Edward P Acosta, Mark N Prichard
1Department of Pediatrics, University of Alabama at Birmingham, AL 35233, USA. dkimberlin@peds.uab.edu
Insights
Determining the correct oseltamivir dosage for infants under two years is crucial for preventing severe influenza. This study establishes appropriate oseltamivir doses for infants aged 0-8 months and 9-11 months, improving pediatric influenza treatment.
Area of Science:
- Pediatric Infectious Diseases
- Pharmacokinetics and Drug Dosing
- Virology
Background:
- Infants under two years face significant risks from influenza, including mortality and severe illness.
- Accurate dosing of antiviral medications like oseltamivir is critical but not well-established for this age group.
Purpose of the Study:
- To determine the appropriate weight-based oral oseltamivir dosage for infants and young children under two years of age.
- To achieve targeted systemic exposure of oseltamivir in pediatric populations.
Main Methods:
- An age-de-escalation, adaptive design study was employed by the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.
- Oseltamivir dosing was evaluated in infants aged less than two years, focusing on achieving specific systemic exposure levels.
Main Results:
- A twice-daily dose of 3.0 mg/kg oseltamivir achieved target exposures in infants aged 0-8 months, with higher variability in those under 3 months.
- A dose of 3.5 mg/kg was required for target exposures in infants aged 9-11 months.
- Some older infants (12-23 months) receiving standard doses had sub-therapeutic drug levels, and three subjects developed oseltamivir resistance.
Conclusions:
- The recommended twice-daily oral oseltamivir dose is 3.0 mg/kg for infants up to 8 months old.
- For infants aged 9-11 months, the recommended twice-daily oral oseltamivir dose is 3.5 mg/kg.
- These findings provide crucial dosing guidelines for oseltamivir in young children to optimize influenza treatment and minimize resistance.
Background:
Children <2 years of age are at high risk of influenza-related mortality and morbidity. However, the appropriate dose of oseltamivir for children <2 years of age is unknown.
Methods:
The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group evaluated oseltamivir in infants aged <2 years in an age-de-escalation, adaptive design with a targeted systemic exposure.
Results:
From 2006 to 2010, 87 subjects enrolled. An oseltamivir dose of 3.0 mg/kg produced drug exposures within the target range in subjects 0-8 months of age, although there was a greater degree of variability in infants <3 months of age. In subjects 9-11 months of age, a dose of 3.5 mg/kg produced drug exposures within the target range. Six of 10 subjects aged 12-23 months receiving the Food and Drug Administration-approved unit dose for this age group (ie, 30 mg) had oseltamivir carboxylate exposures below the target range. Virus from 3 subjects developed oseltamivir resistance during antiviral treatment.
Conclusions:
The appropriate twice-daily oral oseltamivir dose for infants ≤8 months of age is 3.0 mg/kg, while the dose for infants 9-11 months old is 3.5 mg/kg.
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