What are the uses of Phenytoin (antiepileptic drug)?

Uses of Phenytoin

Phenytoin is primarily used as an antiepileptic drug for treating generalized tonic-clonic seizures, partial seizures with or without generalization, and convulsive status epilepticus. 1, 2

Primary Indications

• Seizure Disorders:
  • Generalized tonic-clonic seizures
  • Partial onset seizures (simple partial, complex partial)
  • Secondary generalized tonic-clonic seizures
  • Status epilepticus (particularly as a second-line agent after benzodiazepines)

Mechanism of Action

Phenytoin works by:

• Inhibiting the spread of seizure activity in the motor cortex 1
• Promoting sodium efflux from neurons, stabilizing the threshold against hyperexcitability
• Reducing posttetanic potentiation at synapses
• Blocking voltage-gated sodium channels in neuronal cell membranes 2
• Reducing activity in brain stem centers responsible for tonic-clonic seizures

Administration in Status Epilepticus

For status epilepticus, phenytoin is administered as follows:

• Adults: Loading dose of 18-20 mg/kg IV at maximum rate of 50 mg/minute 3
• Children: 20 mg/kg IV (maximum initial dose: 1000 mg) 3
• Neonates: 10 mg/kg IV 3

Important administration considerations:

• Must be diluted in normal saline (not dextrose solutions)
• Requires continuous monitoring of ECG, blood pressure, and respiratory function
• Infusion rate should be reduced if heart rate decreases by 10 beats per minute 3
• Fosphenytoin (a prodrug of phenytoin) can be administered at 18 PE/kg IV at a maximum rate of 150 PE/min with lower risk of adverse cardiac effects 3, 4

Therapeutic Monitoring

• Therapeutic range: 10-20 mcg/mL 3
• Steady-state levels achieved after 7-10 days (5-7 half-lives) of therapy 1
• Peak serum levels occur 4-12 hours after oral administration 1
• Trough levels should be measured to confirm compliance and effective serum range
• After dose adjustment, allow 7-10 days to reach steady state before rechecking levels 3

Alternative Uses in Dermatology

Though primarily an antiepileptic, phenytoin has been used in dermatology for:

• Treatment of ulcers
• Management of epidermolysis bullosa
• Various inflammatory skin conditions 5
• Wound healing promotion (topical application, though requires further research) 5

Comparative Efficacy

• Phenytoin and valproate show similar efficacy for partial onset and generalized tonic-clonic seizures 6
• For status epilepticus, valproate 30 mg/kg IV is as effective as phenytoin (88% resolution in both groups) but with lower risk of hypotension (0% vs 12%) 3
• Levetiracetam 30 mg/kg IV has similar efficacy to valproate in refractory status epilepticus 3

Important Adverse Effects

Phenytoin has several significant adverse effects:

• Neurological: Ataxia, nystagmus, tremor, somnolence, cognitive impairment 2
• Cardiovascular: Hypotension (12% of patients) and bradycardia, especially with rapid infusion 3
• Dermatological: Gingival hyperplasia, hirsutism, rash, Stevens-Johnson syndrome (rare) 5
• Hematological: Altered clotting function 5
• Metabolic: Altered vitamin and mineral levels 5

Special Considerations

• Protein binding: Normally 90-95% protein-bound; free levels may be altered in patients with different protein binding characteristics 1, 2
• Metabolism: Almost completely metabolized in the liver; exhibits saturable kinetics at high plasma levels 1
• Drug interactions: Concomitant use with enzyme-inducing drugs (phenobarbital, carbamazepine) shortens half-life 2
• Special populations: Requires dose adjustments in renal insufficiency, hepatic insufficiency, and pregnancy 3

Clinical Pearls

• Chronotherapeutic dosing (administering most/all daily dose at 8:00 PM) may improve efficacy and reduce toxicity in some patients 7
• Due to its potential adverse effects, phenytoin is generally not recommended as first-line therapy for epilepsy except in status epilepticus 2
• Fosphenytoin offers improved tolerability over phenytoin with fewer injection site reactions and cardiac complications 4
• Phenytoin is not recommended for long-term use in patients with intellectual disability, loss of locomotion, cognitive impairment, or cerebellar disease 2