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Developmental aspects of phenobarbital dosage requirements in newborn infants with seizures
M C Nahata1, T Masuoka, R C Edwards
1College of Pharmacy, Ohio State University, Columbus 43210.
Insights
New dosage guidelines for phenobarbital in newborns with seizures are established. Premature infants (≤35 weeks) require 3.5-4.5 mg/kg/d, while those >35 weeks need 4.0-5.0 mg/kg/d for therapeutic levels.
Area of Science:
- Neonatal pharmacology
- Pediatric neurology
Background:
- Phenobarbital is a common antiepileptic drug for neonatal seizures.
- Current dosage guidelines lack specificity for varying gestational ages in neonates.
Purpose of the Study:
- To develop age-specific phenobarbital dosage guidelines for newborn infants.
- To determine optimal maintenance doses based on gestational age for seizure control.
Main Methods:
- Studied 51 infants (27 premature, 24 term) during their first month of life.
- Administered phenobarbital doses ranging from 3 to 6 mg/kg/d.
- Monitored serum phenobarbital concentrations throughout therapy.
Main Results:
- Therapeutic phenobarbital levels (15-40 mcg/mL) achieved in 99/114 measurements with doses of 3.5-4.5 mg/kg/d.
- Infants >35 weeks gestation required higher doses (4.0-5.0 mg/kg/d) for therapeutic concentrations.
- Term infants with asphyxia showed higher serum concentrations than those without.
Conclusions:
- Recommended initial phenobarbital maintenance doses: 3.5-4.5 mg/kg/d for infants ≤35 weeks gestation and 4.0-5.0 mg/kg/d for infants >35 weeks.
- Phenobarbital serum concentrations decrease over time, necessitating frequent monitoring.
- Dosage adjustments are crucial for effective seizure management in neonates.
Abstract:
Although phenobarbital is the most widely used drug to control seizures, dosage guidelines are not available for infants of varying gestational ages. The primary objective of this study was to develop age specific dosage guidelines for phenobarbital in newborn infants with seizures. Fifty-one patients (27 premature infants, gestational ages 27 to 38 weeks; 24 term infants) receiving phenobarbital, 3 to 6 mg/kg/d were studied during the first month of life. Multiple serum concentrations were determined in each patient during extended therapy. Trough serum concentration of phenobarbital ranged from 12.5 to 50.2 mcg/mL. Phenobarbital serum concentrations were within therapeutic range (15 to 40 mcg/mL) in 99 of 114 measurements at a maintenance dose of 3.5 to 4.5 mg/kg/d. The remaining 15 measurements were made in infants, greater than 35 weeks' gestation and required phenobarbital doses of 4.0 to 5.0 mg/kg/d to achieve therapeutic serum concentration. These data suggest that the initial maintenance dose of phenobarbital during the first month of life should be 3.5 to 4.5 mg/kg/d in infants less than or equal to 35 weeks and 4.0 to 5.0 mg/kg/d in those greater than 35 weeks' gestation. Term infants with asphyxia had higher trough serum concentration than those without asphyxia (P less than 0.005). In nine infants, trough serum concentration normalized for dose decreased substantially during a 3-weeks period (P less than 0.0005). This suggests that phenobarbital serum concentration should be monitored frequently during the first month of life.