Management overview for phenytoin poisoning

Phenytoin is a broad-spectrum antiepileptic drug. Toxicity following ingestion typically involves dose-related ataxia, confusion and sedation, which resolve gradually over several days. Coma and seizures are rare, even following massive ingestions, and cardiotoxicity is not anticipated.

Phenytoin toxicity may occur as a result of:

• acute large ingestion
• escalation of the dose or repeated supratherapeutic ingestions, in the context of chronic therapy
• co-ingestion with drugs that inhibit the cytochrome P450 enzymes, CYP2C9 and CYP2C19
• patients with a slow-metabolism phenotype; in these patients, the half-life of phenytoin can be up to 10 days.

Phenytoin metabolism is saturable and, in the above scenarios, the half-life of phenytoin is likely to be prolonged. Resolution of toxicity may take days or, in patients with slow phenytoin metabolism, weeks.

Most patients are anticipated to survive phenytoin toxicity with supportive care and the prevention of falls. Electrocardiographic monitoring is not required if the patient is conscious. If possible, stop any drugs that that interact with phenytoin.

Rapid intravenous administration of large doses of phenytoin can cause bradycardia, hypotension and ventricular arrhythmias. This relatively short-lived toxicity is likely mediated by the propylene glycol diluent rather than phenytoin itself, and treatment is supportive care.