Phenytoin Toxicity

Aka: Phenytoin Toxicity, Dilantin Toxicity, Phenytoin Overdose, Phenytoin Poisoning

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II. Causes

  1. Intentional Overdose
  2. Excessive dosing (or Drug Interactions interfering with clearance)

III. Mechanism

  1. Phenytoin is a Class 1B Antiarrhythmic, blocking voltage dependent Sodium channels

IV. Pharmacokinetics

  1. See Phenytoin
  2. Acute oral toxic dose: >20 mg/kg
  3. Phenytoin Half-Life is typically 22 to 24 hours
    1. However, very long Half-Life (zero order elimination) at toxic concentrations (>40 mcg/ml)

V. Signs

  1. Phenytoin level 20 to 30 mcg/ml
    1. Nystagmus on lateral gaze
    2. Smooth Extraocular Movements lost
    3. Sedation
    4. Nausea and Vomiting
  2. Phenytoin level >30 mcg/ml
    1. Vertical Nystagmus
    2. Diplopia
    3. Ataxia or lurching gait
    4. Coarse extremity Tremor
    5. Slurred speech
    6. Altered Level of Consciousness
  3. Phenytoin Level >95 mcg/ml
    1. Lethal (deaths have occurred as low as 50 mcg/ml)
    2. Cardiovascular effects are rare (outside of Intravenous Phenytoin use)

VI. Differential Diagnosis

  1. Posterior fossa tumor
  2. Acute viral cerebellitis
  3. Guillain-Barre Syndrome
  4. Botulism
  5. Anxiety Disorder

VII. Labs: Serial levels

  1. See Unknown Ingestion
  2. Serum Total Phenytoin Level
    1. Although, serum free Phenytoin is available, total Phenytoin level is typically used
  3. Serum Glucose
  4. Serum Creatinine
  5. Urinalysis
  6. Electrocardiogram
  7. Liver Function Tests

VIII. Management

  1. Manage Hypotension
  2. Gastric Decontamination
    1. Activated Charcoal if presents within first 1-2 hours of ingestion
  3. Treat complete Heart Block (rare)
    1. See Symptomatic Bradycardia
    2. See Emergency Cardiac Pacing
  4. Treat Seizures (rare)
    1. See Status Epilepticus
    2. Diazepam 0.1 to 0.3 mg/kg IV to 20 mg/dose
    3. May repeat Diazepam dosing in 20 minutes
  5. Disposition
    1. May discharge home if decreasing serum concentrations, and no Ataxia

IX. References

  1. Tomaszewski (2024) Crit Dec Emerg Med 38(1): 37
  2. Ellenhorn (1997) Medical Toxicology, p. 605-8
  3. Katzung (1989) Pharmacology, p. 289-91

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