Safety of oseltamivir compared with the adamantanes in children less than 12 months of age.
BACKGROUND
When oseltamivir is administered in extremely high doses (500-1000 mg/kg) to young juvenile rats, central nervous system toxicity and death occurred in some animals. Mortality was not observed in older juvenile rats, suggesting a possible relationship between neurotoxicity and an immature blood-brain barrier. To assess potential neurologic adverse effects of oseltamivir use in infants, a retrospective chart review was performed in infants less than 12 months of age who received oseltamivir, amantadine, or rimantadine.


METHODS
The primary objective was to describe the frequency of neurologic adverse events among children less than 12 months of age who received oseltamivir compared with those receiving adamantanes. Medical record databases, emergency department databases, and/or pharmacy records at 15 medical centers were searched to identify patients.


RESULTS
Of the 180 infants identified as having received antiviral therapy, 115 (64%) received oseltamivir, 37 (20%) received amantadine, and 28 (16%) received rimantadine. The median dose of oseltamivir was 2.0 mg/kg/dose in 3- to 5-month-old and 2.2 mg/kg/dose in 9- to 12-month-old infants. The maximum dose administered was 7.0 mg/kg/dose. There were no statistically significant differences in the occurrence of adverse neurologic events during therapy among subjects treated with oseltamivir versus those treated with the adamantanes (P = 0.13).


CONCLUSIONS
This is the largest report to date of oseltamivir use in children less than 12 months of age. Neurologic events were not more common with use of oseltamivir compared with that of the adamantanes. Dosing of oseltamivir was variable, illustrating the need for pharmacokinetic data in this younger population.
Kimberlin
David W
DW
Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Alabama, Birmingham, Birmingham, AL 35233, USA. dkimberlin@peds.uab.edu
Shalabi
Marwan
M
Abzug
Mark J
MJ
Lang
David
D
Jacobs
Richard F
RF
Storch
Gregory
G
Bradley
John S
JS
Wade
Kelly C
KC
Ramilo
Octavio
O
Romero
José R
JR
Shelton
Mark
M
Leach
Charles
C
Guzman-Cottrill
Judith
J
Robinson
Joan
J
Abughali
Nazha
N
Englund
Janet
J
Griffin
Jill
J
Jester
Penny
P
Cloud
Gretchen A
GA
Whitley
Richard J
RJ
D000218:Adamantane / Q000009:adverse effects* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002490:Central Nervous System / Q000187:drug effects; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007251:Influenza, Human / Q000188:drug therapy*; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced; D053139:Oseltamivir / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D012299:Rimantadine / Q000009:adverse effects* / Q000627:therapeutic use
D000998:Antiviral Agents; D012299:Rimantadine; D053139:Oseltamivir; D000218:Adamantane