What is the treatment for phenytoin (antiepileptic) overdose?

From the Guidelines

The treatment for phenytoin overdose involves immediate discontinuation of the drug, supportive care, and specific interventions based on severity, with a focus on cardiac monitoring, blood pressure support, and respiratory support as needed. The management of phenytoin overdose is crucial to prevent morbidity and mortality. For acute ingestions, activated charcoal should be administered within 1-2 hours of ingestion (typically 1g/kg orally) to reduce absorption. Supportive care includes cardiac monitoring for arrhythmias, blood pressure support if hypotension occurs, and respiratory support as needed. Intravenous fluids may be required to maintain hemodynamic stability.

Seizures resulting from phenytoin toxicity should be treated with benzodiazepines such as lorazepam (2-4mg IV) or diazepam (5-10mg IV). For severe cases with significant cardiotoxicity, sodium bicarbonate (1-2 mEq/kg IV) may help reverse cardiac conduction abnormalities by displacing phenytoin from sodium channels, as suggested by the American Heart Association guidelines 1. However, the use of lidocaine or phenytoin as a class Ib antidysrhythmic is not recommended as a first-line therapy for phenytoin overdose, but rather for other sodium channel blocker poisonings 1.

Hemodialysis is generally ineffective due to phenytoin's high protein binding. Regular monitoring of phenytoin levels, complete blood count, and liver function is essential during treatment. The management focuses on supporting vital functions while the drug is naturally eliminated, as phenytoin has a long half-life (typically 12-36 hours) that can be extended in overdose situations. Key interventions include:

• Immediate discontinuation of phenytoin
• Activated charcoal administration for acute ingestions
• Supportive care with cardiac monitoring, blood pressure support, and respiratory support
• Benzodiazepines for seizure management
• Sodium bicarbonate for severe cardiotoxicity
• Regular monitoring of phenytoin levels and vital functions.

From the FDA Drug Label

The lethal dose in pediatric patients is not known. 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. The patient may become comatose and hypotensive. Death is due to respiratory and circulatory depression Treatment is nonspecific since there is no known antidote. The adequacy of the respiratory and circulatory systems should be carefully observed and appropriate supportive measures employed Hemodialysis can be considered since phenytoin is not completely bound to plasma proteins. Total exchange transfusion has been used in the treatment of severe intoxication in pediatric patients.

The treatment for phenytoin overdose is nonspecific and supportive. Key measures include:

• Careful observation of the respiratory and circulatory systems
• Employment of appropriate supportive measures
• Consideration of hemodialysis since phenytoin is not completely bound to plasma proteins
• Total exchange transfusion may be used in severe intoxication in pediatric patients 2.

From the Research

Treatment Overview

The treatment for phenytoin overdose is primarily supportive care, focusing on managing symptoms and preventing further complications.

• The mainstay of therapy includes attention to vital functions, management of nausea and vomiting, and prevention of injuries due to confusion and ataxia 3.
• There is no antidote for phenytoin overdose, and methods of gastrointestinal decontamination or enhanced elimination have limited evidence of improving outcomes 3, 4.

Supportive Care

Supportive care is crucial in managing phenytoin overdose, as it helps alleviate symptoms and prevents secondary complications.

• Meticulous supportive care, including ventilation if necessary, should provide a good clinical outcome 4.
• Activated charcoal may be considered if the patient presents early, but its role in multiple-dose administration is controversial 3, 4.

Enhanced Elimination Methods

Various methods have been explored to enhance the elimination of phenytoin in overdose situations, with mixed results.

• Hemodialysis has been shown to be effective in removing phenytoin from the body, especially in severe cases 5, 6, 7.
• Hemoperfusion, often used in combination with hemodialysis, can also help reduce phenytoin levels 5, 7.
• Other methods like plasmapheresis and peritoneal dialysis have been reported but are not widely recommended due to limited evidence of their effectiveness 5.

Specific Considerations

Certain patient factors and overdose characteristics may influence the choice of treatment.

• In patients with a high free fraction of phenytoin, high-flux dialysis may be a valuable alternative or adjuvant to hemoperfusion 5.
• The use of extracorporeal therapies like hemodialysis and hemoperfusion should be considered in severe cases of phenytoin intoxication, especially when there is significant impairment of renal function or when the patient is critically ill 6, 7.