What are the symptoms of Dilantin (phenytoin) toxicity?

Symptoms of Dilantin (Phenytoin) Toxicity

The primary symptoms of phenytoin toxicity include nystagmus, ataxia, dysarthria, confusion, and lethargy, with more severe cases progressing to coma, hypotension, and respiratory depression. 1

Neurological Symptoms (Most Common)

Neurological symptoms typically appear in a dose-dependent progression:

• Early signs (at levels around 20 mcg/mL):

  • Nystagmus (involuntary eye movement), particularly on lateral gaze 1
  • Dizziness
  • Tremor

• Moderate toxicity (at levels around 30 mcg/mL):

  • Ataxia (loss of coordination) 1
  • Slurred speech (dysarthria)
  • Hyperreflexia 2

• Severe toxicity (at levels over 40 mcg/mL):

  • Confusion and altered mental status 1
  • Lethargy progressing to coma
  • Paradoxical seizures (seizures that occur as phenytoin levels rise) 3

Gastrointestinal Symptoms

• Nausea and vomiting 1, 2
• Constipation 1

Cardiovascular Symptoms

• Hypotension (in severe cases) 1
• Cardiac arrhythmias (rare with oral ingestion, more common with IV administration) 2

Psychiatric/Behavioral Symptoms

• Depression with vegetative symptoms (changes in mood, sleep, and appetite) 4
• Irritability 1
• Nervousness 1

Dermatological Symptoms

• Rash 1
• In chronic toxicity: gingival hyperplasia, hirsutism, coarsening of facial features 5

Rare but Serious Manifestations

• Cerebellar atrophy (with prolonged toxicity) 6
• Persistent cerebellar ataxia even after drug discontinuation 6
• Respiratory depression (in severe overdose) 1

Monitoring for Toxicity

Phenytoin toxicity correlates with serum levels, though individual susceptibility varies:

• Therapeutic range: 10-20 mcg/mL
• Toxic effects typically begin: >20 mcg/mL
• Severe toxicity: >40 mcg/mL 1

Risk Factors for Toxicity

• Dosage adjustments
• Drug interactions (particularly with drugs that inhibit phenytoin metabolism)
• Hypoalbuminemia
• Hepatic dysfunction
• Chronic renal failure 3
• Alcohol consumption (increases risk of hepatotoxicity) 7

Management of Toxicity

1. Discontinue phenytoin or reduce dosage
2. Provide supportive care (no specific antidote exists) 1, 2
3. Monitor respiratory and circulatory systems
4. Consider activated charcoal for recent ingestions
5. In severe cases, hemodialysis may be considered (though phenytoin is protein-bound) 1

Important Pitfalls to Avoid

1. Missing paradoxical seizures: Increased seizure activity can actually be a sign of phenytoin toxicity, not treatment failure 3

2. Overlooking psychiatric symptoms: Depression with vegetative symptoms may be the primary presentation of toxicity in some patients 4

3. Confusing withdrawal with toxicity: Abrupt discontinuation can cause withdrawal seizures; taper medication when discontinuing 1

4. Alcohol interactions: Advise patients that alcohol can increase the risk of toxicity and enhance CNS depression 7

5. Delayed recognition of cerebellar damage: Severe or prolonged toxicity can cause permanent cerebellar damage 6