Serum concentrations and safety of rimantadine in paediatric patients.

Rimantadine has been shown to be more active in vitro and less toxic than amantadine in adults with influenza A disease. Because of a lack of studies in pediatric patients, we designed a study to evaluate serum concentrations and adverse effects of rimantadine in infants receiving repeated doses. Fourteen hospitalized infants (ages 1-10 months) were given rimantadine syrup at 3 mg/kg/dose in single daily doses during influenza season. Blood samples were obtained prior to dose and at various intervals up to 8 h after doses on the fifth to ninth days of therapy. Adverse effects were assessed based on clinical status, activity level, hematologic and biochemical parameters during 10-day therapy. Steady-state rimantadine peak serum concentration ranged from 100 to 574 ng/ml and time to achieve peak concentration ranged from 2.5 to 6.0 h after the doses. No adverse effects were seen except hematuria in one infant; this patient had the highest rimantadine concentration and longest treatment duration. Hematuria resolved during a follow-up evaluation on the ninth day after stopping therapy. Our data suggest that rimantadine can be given safely at repeated doses of 3 mg/kg/dose in a convenient once-daily regimen; the steady-state peak serum concentrations and time to achieve peak concentration may vary substantially in infants receiving same oral doses; and possible association of adverse effects and high serum concentration or long treatment duration of rimantadine needs further evaluation in small infants.