What is the management for Phenytoin (Eptoin) toxicity?

Management of Phenytoin (Eptoin) Toxicity

The management of phenytoin toxicity is primarily supportive care with no specific antidote available, focusing on airway protection, vital sign monitoring, and prevention of injury-related complications. 1

Initial Assessment and Stabilization

Immediately assess and secure the airway, ensure adequate oxygenation and ventilation, and establish continuous cardiac monitoring. 2

• Monitor vital signs closely, particularly for hypotension and cardiac arrhythmias, though these are rare with oral ingestion and more common with IV administration 2, 3
• Correct electrolyte abnormalities, ensuring serum potassium is greater than 4 mEq/L to prevent cardiac complications 2
• Obtain baseline phenytoin level, complete metabolic panel, and ECG 4

Clinical Manifestations by Severity

Toxicity manifests in a dose-dependent pattern based on serum levels:

• Mild toxicity (20-30 mcg/mL): Nystagmus on lateral gaze appears first 1
• Moderate toxicity (30-40 mcg/mL): Ataxia, dysarthria, tremor, hyperreflexia, and slurred speech develop 1, 4
• Severe toxicity (>40 mcg/mL): Lethargy, confusion, depressed consciousness, nausea, vomiting, and potentially coma 1, 4
• Life-threatening toxicity: Seizures (paradoxically), respiratory depression, and circulatory collapse may occur 1, 4

Supportive Management

Provide symptomatic treatment as there is no antidote for phenytoin toxicity: 1

• Airway management: Consider intubation for patients with depressed consciousness or respiratory depression 4
• Prevent injury: Implement fall precautions and close observation due to confusion and ataxia 4
• Manage nausea and vomiting: Administer antiemetics as needed 4
• Maintain normothermia: Monitor and control body temperature 4

Gastrointestinal Decontamination

Activated charcoal may be considered only if the patient presents within 1-2 hours of ingestion and has a protected airway. 4

• Single-dose activated charcoal (1 g/kg, maximum 50 g) can be administered if presentation is early 4
• Multiple-dose activated charcoal remains controversial with no proven clinical benefit despite theoretical increased clearance 4
• Do not induce vomiting due to risk of aspiration and CNS depression 4

Cardiac Management

Avoid administering lidocaine or additional phenytoin to treat any phenytoin-induced arrhythmias, as these may worsen toxicity. 2

• Cardiac complications (arrhythmias, hypotension) are uncommon with oral overdose but require monitoring 4, 3
• If hypotension occurs, administer IV fluid boluses (10 mL/kg normal saline) 4
• Maintain continuous cardiac monitoring, especially in elderly patients or those with cardiovascular comorbidities 3

Enhanced Elimination

There is no evidence that invasive methods of enhanced elimination improve outcomes in phenytoin toxicity. 4

• Hemodialysis, hemoperfusion, and plasmapheresis are not recommended as phenytoin is highly protein-bound (90-95%) with a large volume of distribution 1, 4
• Total exchange transfusion has been used in severe pediatric intoxication but lacks evidence of benefit 1

Special Considerations

Phenytoin exhibits zero-order (saturation) kinetics in overdose, resulting in a greatly prolonged half-life and extended duration of symptoms. 4, 5

• Expect prolonged hospitalization due to extended elimination time 4
• Monitor for drug interactions, particularly with clarithromycin, erythromycin, and other medications that can precipitate toxicity 2
• Neonates and young infants have increased toxicity risk due to decreased protein binding and altered pharmacokinetics 2
• Consider co-ingestions, especially CNS depressants and alcohol, which may complicate management 1

Monitoring and Disposition

Serial phenytoin levels should be obtained every 4-6 hours initially, then daily until declining, to guide duration of observation. 4

• Patients with severe toxicity (levels >40 mcg/mL) or CNS depression require ICU admission 4
• Asymptomatic patients with mild elevation may be observed in a monitored setting 4
• Discharge is appropriate only when phenytoin levels are declining, the patient is ambulatory without ataxia, and mental status has normalized 4

Critical Pitfalls to Avoid

• Do not administer more phenytoin or phenytoin-like drugs (including fosphenytoin) to treat paradoxical seizures from toxicity 2
• Avoid rapid IV administration if phenytoin must be given for another indication, as rates >50 mg/min significantly increase mortality risk 3
• Do not assume benign course - deaths can occur from respiratory and circulatory depression, though they are unlikely with oral ingestion alone 1, 4
• Monitor for phenytoin encephalopathy in chronic toxicity, which may cause permanent cognitive impairment and cerebellar syndrome 5