What is the use of phenytoin (antiepileptic medication) in neonates (newborns)?

Phenytoin Use in Neonates

In neonates with seizures, phenobarbital should be used as first-line treatment rather than phenytoin, as phenytoin has an increased risk of toxicity in neonates due to decreased protein binding. 1

Indications and Dosing

Phenytoin may be used in neonates primarily as a second-line agent for status epilepticus when first-line therapy fails. The recommended dosing is:

• Status epilepticus in neonates: 10 mg/kg IV 1
• Recommended infusion time: 10-20 minutes
• Maximum infusion rate: 1 mg/kg per minute

Administration Considerations

When administering phenytoin to neonates, several important precautions must be taken:

• Phenytoin must be diluted in normal saline (not glucose-containing solutions) to avoid precipitation 1
• Monitor heart rate continuously during infusion; reduce infusion rate if heart rate decreases by 10 beats per minute
• Be prepared to provide respiratory support due to increased risk of apnea, especially when combined with other sedative agents 1
• Monitor oxygen saturation throughout administration

Efficacy and Safety Concerns

Phenytoin has limited efficacy in neonatal seizures:

• In direct comparison studies, phenytoin controlled seizures in only 45% of neonates, similar to phenobarbital's 43% efficacy 2
• The International League Against Epilepsy (ILAE) Task Force on Neonatal Seizures recommends phenobarbital as first-line treatment for neonatal seizures 3
• Phenytoin should only be considered first-line if a channelopathy is the likely cause of seizures 3

Safety Concerns Specific to Neonates

• Neonates have increased risk of toxicity due to decreased protein binding 1
• May cause hypotension and cardiac arrhythmias, especially with rapid infusion 1
• If available, fosphenytoin is preferred due to lower risk of adverse cardiac effects 1
• FDA labeling notes significant risks during pregnancy including fetal hydantoin syndrome, which can cause craniofacial anomalies, nail and digital hypoplasia, growth deficiency, and neurodevelopmental deficiencies 4

Alternative Agents

When considering treatment options for neonatal seizures:

1. First-line agent: Phenobarbital (evidence-based recommendation) 3
2. Second-line options (if seizures persist):
   • Phenytoin
   • Levetiracetam
   • Midazolam
   • Lidocaine 3

For neonates with cardiac disorders, levetiracetam may be the preferred second-line agent 3.

Practical Algorithm for Neonatal Seizure Management

1. First seizure episode: Start with phenobarbital (not phenytoin)
2. If seizures continue after adequate phenobarbital dosing:
   • For most neonates: Consider phenytoin at 10 mg/kg IV
   • For neonates with cardiac disorders: Consider levetiracetam instead
   • For suspected channelopathy: Consider phenytoin or carbamazepine as first-line 3
3. If seizures remain uncontrolled: Consider combination therapy or alternative agents like midazolam or lidocaine 5
4. After acute seizure control: Discontinue antiseizure medications before discharge home if seizures were acute provoked events without evidence of neonatal-onset epilepsy 3

Common Pitfalls to Avoid

• Never mix phenytoin with glucose-containing solutions (causes precipitation)
• Avoid rapid infusion in neonates due to increased risk of cardiac complications
• Do not continue phenytoin long-term after acute provoked seizures without evidence of epilepsy
• Be aware of drug interactions as phenytoin is metabolized by the liver and can affect metabolism of other medications

Phenytoin should be used cautiously in neonates, with phenobarbital remaining the preferred first-line agent for most neonatal seizures due to safety considerations.