Phenytoin toxicity


  • Mortality is extremely rare after intentional overdose if good supportive care is provided
  • Rapid IV dosing carries greatest risk (due to propylene glycol constituent of IV form → myocardia depression & cardiac arrest)
  • 90% protein bound; dialysis ineffective

Clinical Features

Differential Diagnosis


Toxicity symptoms by phenytoin level^

Level Sypmtoms
>10 Usually no symptoms
10-20 Occasional mild nystagmus
20-30 Nystagmus
30-40 Ataxia, slurred speech, Nausea/vomiting
40-50 Lethargy, confusion
>50 Coma, seizure (rare)

^Provides a rough guide only; neither sensitive nor specific

  • Correct for albumin level
    • Free phenytoin concentration determines toxicity
    • Hypoalbuminemia results in higher free phenytoin concentration
  • Other laboratory testing
    • LFTs, hepatic dysfunction increases risk of phenytoin toxicity
    • CBC, frequently show eosinophilia or marked leukocytosis
    • Total CK
    • ECG, may see arrhythmias, AV block, or sinus arrest with junctional or ventricular escape
    • POC glucose, rule out hypoglycemia as cause of AMS
    • Acetaminophen and salicylate levels, rule out common coingestion
    • Urine pregnancy test



  • Cannot base on phenytoin level (erratic absorption after PO overdose)
    • Consider discharge if patient has only mild symptoms and serial phenytoin levels decline

See Also