What are all the uses of Phenytoin?

Uses of Phenytoin

Phenytoin is primarily used for treating epilepsy, particularly generalized tonic-clonic seizures, partial seizures with or without generalization, and status epilepticus, with its primary mechanism of action being the modulation of voltage-gated sodium channels in neuronal cell membranes. 1, 2

Primary Indications

• Seizure Management:

  • Generalized tonic-clonic seizures
  • Partial seizures (simple partial, complex partial)
  • Status epilepticus (as part of treatment protocol)
  • Serial seizures

• Specific Clinical Scenarios:

  • Seizure prophylaxis after subarachnoid hemorrhage
  • Management of seizures in alcohol withdrawal
  • Treatment of refractory status epilepticus (high-dose phenytoin up to 30 mg/kg)

Dosing Protocols

Adult Dosing

• Standard maintenance dosage: 300-400 mg/day (typically one 100-mg capsule three to four times daily)
• Once-daily dosing option: 300 mg daily (only with extended phenytoin sodium capsules)
• Loading dose: 1 gram divided into three doses (400 mg, 300 mg, 300 mg) administered at two-hour intervals in controlled settings 1

Pediatric Dosing

• Initial dose: 5 mg/kg/day in two or three equally divided doses
• Maintenance dose: 4-8 mg/kg/day (maximum 300 mg daily)
• Children >6 years: May require minimum adult dose (300 mg/day) 1

Status Epilepticus Dosing

• Standard dose: 18-20 mg/kg IV with 56% success rate
• High-dose option: Up to 30 mg/kg (as recommended by the Epilepsy Foundation of America's Working Group) before switching to alternative agents 3, 4

Pharmacokinetics

• Plasma half-life: Averages 22 hours (range 7-42 hours)
• Steady-state achievement: 7-10 days after initiation of therapy
• Protein binding: 90-95% protein-bound in plasma
• Therapeutic serum levels: 10-20 mcg/mL
• Metabolism: Almost completely metabolized in the liver 1, 2

Comparative Efficacy

• Phenytoin shows comparable efficacy to valproate for partial onset seizures and generalized tonic-clonic seizures 5
• In status epilepticus, phenobarbital has shown equal efficacy when compared with lorazepam, phenytoin, and phenytoin plus diazepam 3

Administration Routes

• Oral: Extended capsules, prompt capsules, suspension
• Intravenous: Direct IV administration (requires careful monitoring)
• Intramuscular: Fosphenytoin (prodrug) can be administered IM with complete absorption and rapid conversion to phenytoin 6

Monitoring Requirements

• Serum level monitoring: Recommended when:
  • Initiating therapy (after 7-10 days)
  • Changing dosage
  • Adding/removing other medications
  • Suspecting toxicity or non-compliance
• Trough levels: Obtained just before next scheduled dose
• Peak levels: 4-12 hours after administration 1

Adverse Effects and Cautions

• Neurological: Phenytoin encephalopathy, cognitive impairment, cerebellar syndrome
• Cardiovascular: Hypotension, cardiac dysrhythmias
• Local reactions: Purple glove syndrome (with IV administration)
• Long-term concerns: Not recommended for patients with:
  • Loss of locomotion
  • Marked cognitive impairment
  • Symptoms of cerebellar disease
  • Intellectual disability (may exacerbate balance disturbances) 4, 2

Special Considerations

• Saturation kinetics at high plasma levels can lead to disproportionate increases in serum levels with small dose increases
• Careful monitoring needed when switching between different phenytoin formulations due to differences in bioavailability
• Not recommended as first-line therapy except in status epilepticus management 1, 2

Phenytoin's primary mechanism of action involves inhibiting voltage-sensitive sodium channels in the plasma membrane of neurons, which stabilizes the threshold against hyperexcitability and prevents the spread of seizure activity 7.

AI Assistant: I've provided a comprehensive overview of phenytoin's uses, focusing on its primary role in seizure management while including important information about dosing, monitoring, and safety considerations.