What are the symptoms of phenytoin (Dilantin) toxicity?

Symptoms of Phenytoin Toxicity

Phenytoin toxicity primarily manifests as nystagmus, ataxia, and dysarthria, with progression to more severe neurological symptoms as serum levels increase above therapeutic range. 1, 2

Clinical Manifestations by Serum Level

Phenytoin toxicity symptoms correlate with serum drug levels:

• Early/Mild Toxicity (20-30 mcg/mL)

  • Nystagmus (especially on lateral gaze) - first clinical sign 1
  • Dizziness/vertigo 3
  • Drowsiness 3

• Moderate Toxicity (30-40 mcg/mL)

  • Ataxia and unsteady gait 1, 3
  • Slurred speech (dysarthria) 1
  • Decreased coordination 4
  • Tremor 5
  • Hyperreflexia 4

• Severe Toxicity (>40 mcg/mL)

  • Lethargy progressing to confusion 1, 3
  • Severe limb ataxia 5
  • Nausea and vomiting 1, 3
  • Diplopia 4
  • Coma (in extreme cases) 1

Unique and Paradoxical Effects

• Paradoxical seizures - seizures that occur as phenytoin levels rise and decrease when levels drop 6
• Cardiovascular effects - rare with oral phenytoin but may include:
  • Hypotension
  • Cardiac arrhythmias (more common with IV administration) 2

Long-term Complications

• Prolonged exposure to toxic levels may lead to:
  • Cerebellar atrophy
  • Persistent cerebellar ataxia even after drug discontinuation 5

Important Clinical Considerations

• Due to zero-order pharmacokinetics, phenytoin has a greatly increased half-life in overdose, resulting in prolonged symptoms 2
• Toxicity can occur from:
  • Intentional overdose
  • Dosage adjustments
  • Drug interactions
  • Excessive self-medication
  • Misunderstanding of prescription orders 3
  • Hypoalbuminemia, chronic renal failure, and hepatic dysfunction 6

Common Misdiagnoses

• Brainstem or cerebellar stroke (most common misdiagnosis, 14% of cases) 3
• Other neurological disorders due to prominent cerebellar signs

Clinical Pearls

• Phenytoin toxicity is often underdiagnosed in emergency settings 3
• Symptoms may persist for a week or more due to prolonged elimination 4
• The unsteady gait increases risk of falls and injuries 3
• Phenytoin can increase serum levels of other medications, including other phenytoin preparations 7
• Monitoring for toxicity should include visual acuity, red-green color discrimination, and liver function tests 7

The management of phenytoin toxicity primarily involves temporary withdrawal of the medication and supportive care, as there is no specific antidote 2, 3.