UMEM Educational Pearls

Category: Toxicology

Title: Acute Phenytoin Toxicity

Keywords: Dilantin, Ataxia (PubMed Search)

Posted: 3/16/2017 by Kathy Prybys, DO
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Phenytoin is a first line anticonvulsant agent for most seizure disorders with the exception of absence and toxin-induced seizures. It has erratic gastrointestinal absorption with peak serum levels occurring anywhere from 3-12 hours following a single oral dose. 90% of circulating phenytoin is bound to albumin but only the unbound free fraction is active to cross cell membranes and exert pharmacological effect. Measured serum phenytoin levels reflect the total serum concentration of both the free and protein bound portions. Therapeutic range is between 10-20 mg/L. Free phenytoin levels are not often measured but are normally between 1-2 mg/L. Individuals with decreased protein binding (elderly, malnourished, hypoalbuminemia, uremia, and competing drugs) may have clincial toxicity despite a normal total phenytoin level. Toxicity consists of predominantly ocular and neurologic manifestations involving the vestibular and cerebellar systems:

Plasma level, µg/mL    Clinical manifestations
<10     Usually none
10-20     Occasional mild nystagmus
20-30     Nystagmus
30-40     Ataxia, slurred speech, extrapyramindal effects 
40-50     Lethargy, confusion
>50     Coma, rare seizures

Treatment of overdose is primarily supportive with serial drug level testing and neurologic exams. There is no evidence that gastrointestinal decontamination improves outcome. Routine cardiac monitoring is not necessary for overdose following oral ingestions. Cardiac toxicity is rarely seen and only with parenteral administration. 


Phenytoin posisoning. Craig S. Neurocrit Care. 2005;3(2): 161-70. 

Severe oral phenytoin overdose does not cause cardiovascular morbidity. Wyte CD, et al. Annals of EM. 1997; 20(5). 508-512.

Cardiac Monitoring after phenytoin overdose. Evers M, et al. Heart & Lung. 1997; 26:325-328.