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Antiepileptic — Status Epilepticus (Second-Line) Pregnancy: Avoid if possible — teratogenic (fetal hydantoin syndrome); register with UK Epilepsy and Pregnancy Register

Phenytoin / Fosphenytoin

Brand names: Epanutin (phenytoin), Pro-Epanutin (fosphenytoin)

Adult dose

Dose: Phenytoin: 15-18 mg/kg IV at max 50 mg/min. Fosphenytoin: 15-18 mg PE/kg IV at max 150 mg PE/min
Route: Intravenous
Frequency: Single loading dose
Max: 1500 mg (phenytoin); 1500 mg PE (fosphenytoin)
NICE NG217 / APLS: Second-line in established status epilepticus after two benzodiazepine doses have failed. Fosphenytoin is prodrug of phenytoin — faster infusion rate, less cardiac toxicity, can be given IM. Dilute phenytoin in normal saline only (precipitates in glucose)

Paediatric dose

Dose: 18-20 mg/kg IV (phenytoin); 18-20 mg PE/kg (fosphenytoin) mg/kg
Route: IV (slow) / IM (fosphenytoin only)
Frequency: Single loading dose
Max: 1500 mg total
Child any age: 18-20 mg/kg IV at max 1 mg/kg/min (phenytoin); 18-20 mg PE/kg fosphenytoin at max 2-3 mg PE/kg/min. Continuous ECG monitoring mandatory

Dose adjustments

Renal

Fosphenytoin: free phenytoin fraction increases in renal impairment — monitor levels

Hepatic

Reduce dose and monitor carefully in hepatic impairment

Paediatric weight-based calculator

Child any age: 18-20 mg/kg IV at max 1 mg/kg/min (phenytoin); 18-20 mg PE/kg fosphenytoin at max 2-3 mg PE/kg/min. Continuous ECG monitoring mandatory

Clinical pearls

  • Fosphenytoin (Pro-Epanutin) is preferred over phenytoin in ED — can be infused 3x faster, given IM, and causes less cardiac toxicity and injection site reactions; dosed in phenytoin equivalents (PE)
  • Purple glove syndrome: phenytoin extravasation causes ischaemia, oedema, and tissue necrosis — use large vein or central line; fosphenytoin avoids this complication
  • Cardiac monitoring mandatory during infusion — rate-related bradycardia and hypotension; slow infusion or stop if arrhythmia develops
  • Phenytoin saturates metabolism at therapeutic levels (zero-order kinetics above 10 micromol/L) — small dose increases cause disproportionate rises in plasma levels; narrow therapeutic index
  • Current NICE NG217 preference: levetiracetam IV or valproate IV are alternatives to phenytoin with comparable evidence and better tolerability

Contraindications

  • Sinus bradycardia or second/third degree heart block
  • Sinoatrial block
  • Porphyria

Side effects

  • Cardiac arrhythmias (if infused too fast — bradycardia, heart block)
  • Hypotension (IV infusion)
  • Purple glove syndrome (phenytoin extravasation — tissue necrosis)
  • CNS depression
  • Nystagmus
  • Ataxia
  • Gingival hyperplasia (chronic)

Interactions

  • Extensive interactions — CYP inducer: reduces levels of warfarin, oral contraceptives, valproate, carbamazepine, steroids, ciclosporin
  • Valproate (increases free phenytoin — toxicity risk)
  • Amiodarone (increases phenytoin levels)

Monitoring

  • ECG (continuous during infusion)
  • Blood pressure
  • Serum phenytoin levels
  • Respiratory rate
  • Neurological status

Reference: BNFc; BNF 90; NICE NG217 (Epilepsy); APLS Guidelines; RCPCH Status Epilepticus Pathway. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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