Phenytoin Toxicity Workup

Updated: Jan 26, 2023
  • Author: Charlene Miller, MD; Chief Editor: David Vearrier, MD, MPH  more...
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Laboratory Studies

Obtain a serum phenytoin level. The therapeutic range is 10-20 mcg/mL. Total phenytoin levels (mcg/mL) and typical corresponding signs and symptoms are as follows:

  • Lower than 10 - Rare
  • Between 10 and 20 - Occasional mild nystagmus
  • Between 20 and 30 - Nystagmus
  • Between 30 and 40 - Ataxia, slurred speech, nausea, and vomiting
  • Between 40 and 50 - Lethargy and confusion
  • Higher than 50 - Coma and seizures

Following an acute overdose, serial serum phenytoin concentrations should be obtained due to unpredictable absorption patterns. Zero-order pharmacokinetics at elevated serum phenytoin concentrations may result in prolonged elevated concentrations lasting days to weeks.

Normally, approximately 90% of circulating phenytoin is bound to albumin. Therapeutic free phenytoin levels are 1 - 2 mcg/mL. Individuals with decreased protein binding may have clincial toxicity despite a normal total phenytoin level; however, their free phenytoin level is elevated. Free phenytoin levels thus may be more accurate than total levels in patients with hypoalbuminemia; alternatively, in such cases the total phenytoin level can be corrected, using the Sheiner-Tozer formula (see Phenytoin level). [9] However, the predictive performance of such formulas has been called into question. [10]

In the intentional overdose setting, immediately perform a dextrose fingerstick test in any patient with altered mental status.

Obtain aspirin and acetaminophen levels in cases of self-injurious or exploratory ingestions when there is a possibility for co-ingestion of those medications. Consider measurement of other drugs the patient is taking, in view of the possibility of drug interactions with phenytoin (see Diagnostic Considerations).

Perform pregnancy tests in women of childbearing age.

For acute toxicity, do the following:

  • Measure ethanol level for multiple ingestions or altered mental status

  • Measure electrolyte levels for questionable clinical presentation, elderly persons, or patients with multiple medical problems

For patients with hypersensitivity reactions, including possible DRESS syndrome, do the following:

  • Obtain a complete blood count (CBC) to rule out anemia, eosinophilia, atypical lymphocytosis, and pancytopenia
  • Perform liver function tests (LFTs) to rule out hepatotoxicity


Imaging Studies

Obtain a CT scan of the head for patients with unexplained altered mental status.

Evaluate patients with a history of ataxia and consequent fall(s) for any traumatic injury.



Oral phenytoin overdose rarely causes cardiac toxicity. Check for evidence of dysrhythmia, severe clinical presentation, or multiple medication ingestion. Most cardiovascular complications have occurred with rapid (>50 mg/min) intravenous administration.