Inadequacy of FDA Dosing Guidelines for Theophylline Use in Neonates

Abstract

The efficacy of the FDA guidelines for theophylline dosing in newborns was evaluated retrospectively in 224 patients who had clearance data available. Mean projected post loading dose serum concentration was 4.1 ± 1.0 mg/L in 160 patients. Mean projected steady-state concentration was 4.8 ± 1.6 mg/L in 189 patients receiving intravenous aminophylline and 4.2 ± 1.3 mg/L in 35 patients on oral therapy. Projected serum concentrations were subtherapeutic (<6.0 mg/L) in 181 of the 224 patients analyzed. There was a statistically significant difference in serum concentrations between asphyxiated and nonasphyxiated patients (p<0.001). There was no significant difference in mean projected serum concentrations between patients age 26–41 weeks (postconceptional age). This study suggests that the FDA dosing guidelines for theophylline in infants is inadequate and results in subtherapeutic (<6.0 mg/L) serum concentrations in the majority of newborns.