From the Guidelines
Dilantin (phenytoin) toxicity should be managed by immediately checking phenytoin levels and discontinuing or reducing the dose as appropriate, with hospitalization necessary for severe cases. Signs of toxicity include nystagmus, ataxia, slurred speech, confusion, and in severe cases, seizures or coma 1. Treatment is primarily supportive, as there is no specific antidote. Factors that increase risk of toxicity include liver disease, hypoalbuminemia, drug interactions (especially with medications that compete for protein binding or inhibit CYP2C9/CYP2C19), and genetic variations affecting metabolism.
Key Considerations
- Phenytoin follows zero-order kinetics at therapeutic doses, meaning small dose increases can cause disproportionate rises in blood levels 1.
- Regular monitoring of drug levels is essential, particularly after dose adjustments or when adding potentially interacting medications.
- Patients should be educated about toxicity symptoms and advised to seek immediate medical attention if they develop.
Management
- For severe toxicity, consider alternative antiepileptic medications such as valproate, which may be given more quickly with fewer adverse effects compared to phenytoin or fosphenytoin 1.
- Be aware of the potential adverse effects of phenytoin, including soft tissue injury with extravasation, hypotension, cardiac dysrhythmias, and purple glove syndrome 1.
From the FDA Drug Label
The lethal dose in adults is estimated to be 2 to 5 grams. The initial symptoms are nystagmus, ataxia, and dysarthria. Other signs are tremor, hyperreflexia, lethargy, slurred speech, nausea, vomiting. Nystagmus, on lateral gaze, usually appears at 20 mcg/mL, ataxia at 30 mcg/mL; dysarthria and lethargy appear when the plasma concentration is over 40 mcg/mL, but as high a concentration as 50 mcg/mL has been reported without evidence of toxicity
Dilantin toxicity symptoms include:
- Nystagmus (usually appears at 20 mcg/mL)
- Ataxia (usually appears at 30 mcg/mL)
- Dysarthria and lethargy (usually appear when the plasma concentration is over 40 mcg/mL)
- Tremor
- Hyperreflexia
- Slurred speech
- Nausea
- Vomiting The estimated lethal dose in adults is 2 to 5 grams 2.
From the Research
Causes of Dilantin Toxicity
- Intentional overdose, dosage adjustments, drug interactions, or alterations in physiology can lead to Dilantin toxicity 3
- Excessive self-medication, misunderstanding of the prescription order, and probable drug interaction are common causes of acute phenytoin intoxication 4
Symptoms of Dilantin Toxicity
- Nausea, central nervous system dysfunction (particularly confusion, nystagmus, and ataxia), with depressed conscious state, coma, and seizures occurring in more severe cases 3
- Unsteady gait, dizziness/vertigo, nausea/vomiting, general weakness, and drowsiness are common presenting symptoms 4
- Cardiovascular complications such as arrhythmias and hypotension are rare in cases of phenytoin ingestion, but may be seen in parenteral administration of phenytoin or fosphenytoin 3, 5
Treatment of Dilantin Toxicity
- The mainstay of therapy for a patient with phenytoin intoxication is supportive care, including attention to vital functions, management of nausea and vomiting, and prevention of injuries due to confusion and ataxia 3
- Temporary withdrawal of phenytoin and supportive care are effective in managing acute phenytoin intoxication 4
- Activated charcoal may be considered if the patient presents early, but its role in multiple-dose administration is controversial 3
- There is no evidence that any invasive method of enhanced elimination (such as plasmapheresis, hemodialysis, or hemoperfusion) provides any benefit 3
Prevention of Dilantin Toxicity
- Nurses should thoroughly familiarize themselves with the properties of phenytoin to practice safely and avoid serious side effects and interactions with numerous other medications 6
- A careful follow-up of heart rhythm and blood pressure is recommended when administering intravenous phenytoin, especially in old patients and patients with cardiovascular co-morbidity 5