Phenytoin toxicity may result from intentional overdose, dosage adjustments, drug interactions, or alterations in physiology. Intoxication manifests predominantly as
nausea, central nervous system dysfunction (particularly
confusion, nystagmus, and
ataxia), with depressed conscious state,
coma, and
seizures occurring in more severe cases. Cardiac complications such as arrhythmias and
hypotension are rare in cases of
phenytoin ingestion, but they may be seen in parenteral administration of
phenytoin or
fosphenytoin. Deaths are unlikely after
phenytoin intoxication alone. A greatly increased half-life in overdose due to zero-order pharmacokinetics can result in a prolonged duration of symptoms and thus prolonged hospitalization with its attendant complications. The mainstay of
therapy for a patient with
phenytoin intoxication is supportive care. Treatment includes attention to vital functions, management of
nausea and
vomiting, and prevention of
injuries due to
confusion and
ataxia. There is no
antidote, and there is no evidence that any method of gastrointestinal decontamination or enhanced elimination improves outcome.
Activated charcoal should be considered if the patient presents early; however, the role of multiple-dose
activated charcoal is controversial. Experimental studies have proven increased clearance rates, but this effect has not been translated into clinical benefit. There is no evidence that any invasive method of enhanced elimination (such as
plasmapheresis,
hemodialysis, or
hemoperfusion) provides any benefit. This article provides an overview of
phenytoin pharmacokinetics and the clinical manifestations of toxicity, followed by a detailed review of the various treatment modalities.