What is the recommended dosage and administration of Phenytoin (antiepileptic medication) for seizure control?

Phenytoin Dosing and Administration for Seizure Control

For status epilepticus in adults, phenytoin should be administered intravenously at 20 mg/kg (maximum 1000 mg) infused over 10-20 minutes at a rate not exceeding 1 mg/kg/min, with potential for a repeat dose of 10 mg/kg if needed after 15 minutes. 1

Adult Dosing Regimens

Status Epilepticus

• IV loading dose: 20 mg/kg (maximum 1000 mg)
• Infusion rate: Not to exceed 1 mg/kg/min (typically over 10-20 minutes)
• Repeat dose: May give additional 10 mg/kg if seizures persist after 15 minutes (maximum total dose: 30 mg/kg) 1

Maintenance Therapy

• Oral dosing (divided): 100 mg three times daily initially, adjusted to 300-400 mg/day in 3-4 divided doses 2
• Once-daily dosing: 300 mg once daily (only recommended with extended phenytoin sodium capsules after seizure control is established with divided doses) 2
• Oral loading dose: 1 gram divided into three doses (400 mg, 300 mg, 300 mg) administered at two-hour intervals, followed by normal maintenance dosing 24 hours later (only in monitored settings) 2

Pediatric Dosing

• Status epilepticus: 20 mg/kg IV (10 mg/kg for neonates) 1
• Maintenance: Initially 5 mg/kg/day in 2-3 divided doses, typically 4-8 mg/kg/day maintenance (maximum 300 mg/day) 2
• Children over 6 years may require minimum adult dose (300 mg/day) 2

Administration Considerations

Intravenous Administration

• Dilute in normal saline only (incompatible with glucose-containing solutions) 1
• Monitor heart rate during infusion; reduce rate if heart rate decreases by 10 beats/min 1
• Monitor blood pressure continuously with arterial line if possible 1
• If 50% QRS widening or hypotension occurs, hold remaining dose 1

Safety Precautions

• Fosphenytoin is preferred when available due to lower risk of adverse cardiac effects 1
• IV phenytoin can cause hypotension, arrhythmias, purple glove syndrome, and tissue necrosis 1
• Parenteral phenytoin contains propylene glycol (40%) and ethanol (10%) with pH of 12, contributing to adverse effects 1

Therapeutic Monitoring

• Target serum concentration: 10-20 mcg/mL 2, 3
• Steady-state levels typically achieved in 7-10 days; avoid dosage changes at intervals shorter than 7-10 days 2
• Monitor serum levels when changing between different phenytoin formulations (sodium salt vs. free acid) 2
• When serum concentration reaches 5-10 μg/mL, make small dose adjustments (approximately 25 mg) due to non-linear pharmacokinetics 3

Special Considerations

Formulation Differences

• Extended phenytoin sodium capsules contain sodium salt of phenytoin
• Suspension and infatabs contain free acid form (8% higher drug content)
• Dosage adjustments and serum monitoring necessary when switching between forms 2

Chronotherapeutic Dosing

• Administering most or all daily dose at 8:00 PM may improve seizure control and reduce toxicity in patients with subtherapeutic levels or experiencing toxicity 4

Potential Adverse Effects

• Dose-related: ataxia, nystagmus, tremor, somnolence 1
• IV administration: hypotension, cardiac arrhythmias, phlebitis 1
• Rare but serious: paradoxical seizures with rapid IV infusion, blood dyscrasias 5

Common Pitfalls and Caveats

• Avoid rapid IV infusion (>1 mg/kg/min) which increases risk of cardiac complications and paradoxical seizures 1, 5
• Do not mix phenytoin with glucose-containing solutions (causes precipitation) 1
• Be aware of non-linear pharmacokinetics - small dose increases may cause disproportionate rises in serum levels 3
• Once-daily dosing should only be used with extended phenytoin sodium capsules, not with other phenytoin products 2
• Patients with renal or liver disease should not receive oral loading regimens 2
• Valproate may be more effective than phenytoin for refractory status epilepticus with fewer adverse effects 1

By following these guidelines, phenytoin can be safely and effectively administered for seizure control while minimizing the risk of adverse effects and optimizing therapeutic outcomes.