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Phenytoin dosing and serum concentrations in paediatric patients requiring 20 mg/kg intravenous loading

Joe D Piper1, Daniel B Hawcutt2, George K Verghese1

  • 1Department of Neurology, Alder Hey Children's Hospital, Liverpool, UK.

Archives of Disease in Childhood
|January 17, 2014
PubMed

Insights

The new 20 mg/kg intravenous loading dose of phenytoin for pediatric status epilepticus can lead to supra-therapeutic serum concentrations due to inaccurate weight estimations. This highlights potential safety concerns and dosing inaccuracies in clinical practice.

Area of Science:

  • Pediatric pharmacology
  • Clinical pharmacy
  • Neurology

Background:

  • Phenytoin exhibits complex pharmacokinetics, necessitating precise dosing.
  • The intravenous loading dose for pediatric status epilepticus was recently raised to 20 mg/kg.
  • Limited data exist on the clinical effectiveness and safety of this updated phenytoin dosage.

Purpose of the Study:

  • To audit the use of intravenous loading doses of phenytoin.
  • To evaluate the pharmacokinetic, clinical, and toxic effects of the new 20 mg/kg dose in pediatric patients.
  • To compare serum phenytoin concentrations with weight-adjusted doses and time post-infusion.

Main Methods:

  • Retrospective and prospective audit of phenytoin loading doses over 27 months.
  • Measurement of serum phenytoin concentrations in children.
  • Comparison of measured concentrations against dose (weight-adjusted) and time.

Main Results:

  • Serum phenytoin concentrations were measured in 41 children; 24 were within 60-180 minutes post-infusion.
  • Weight estimations resulted in doses ranging from 78% to 138% of the expected dose.
  • Supra-therapeutic concentrations (>20 µg/mL) occurred in 20.1% of patients, with associated adverse effects in three cases.

Conclusions:

  • While most serum phenytoin concentrations were therapeutic, weight estimation inaccuracies are common.
  • The 20 mg/kg intravenous loading dose can lead to significantly higher than recommended doses in children.
  • Dosing inaccuracies necessitate careful consideration of weight-based calculations for phenytoin in pediatric status epilepticus.
Abstract

Keywords:
Accident & EmergencyAuditNeurologyPharmacologyTherapeutics

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