Phenytoin Toxicity Clinical Presentation

Updated: Jan 26, 2023
  • Author: Charlene Miller, MD; Chief Editor: David Vearrier, MD, MPH  more...
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Establish whether the toxicity is acute or chronic. Important historical elements in acute toxicity are as follows:

  • Time of ingestion
  • Co-ingestants
  • Motivation for ingestion (intentional versus accidental)
  • Medications available in the household

Paramedics or family members may be able to provide additional information (eg, medications, past medical history)

In chronic toxicity, important historical elements are as follows:

  • Duration of phenytoin use
  • Dosing
  • Frequency
  • Compliance (last dose and missed dose)
  • Recent changes in pharmacotherapy

Important elements for patient query are as follows:

  • When symptoms began
  • Severity of symptoms
  • Exacerbating factors
  • Associated problems
  • Relieving factors

Physical Examination

Gingival hyperplasia is the most common adverse effect (20%) seen with chronically elevated serum phenytoin concentrations but is not associated with acute toxicity.

Neurologic findings in phenytoin toxicity may include the following:

  • Hyperreflexia or hyporeflexia
  • Abnormal gait (bradykinesia, truncal ataxia - Ataxia is very typical with elevated phenytoin levels, and may lead to falls and consequent trauma
  • Encephalopathy
  • Meningeal irritation with pleocytosis
  • Tremor (intention)
  • Irritability or agitation
  • Confusion
  • Hallucinations
  • Mental status varies from completely normal to the extremes of stupor and coma, particularly if co-ingestants are present
  • Peripheral neuropathy (long-term use)
  • Priapism
  • Urinary incontinence
  • Choreoathetoid movements
  • Dysarthria
  • Dysphagia
  • Seizures (rare)
  • Death (rare)

Eye examination may reveal the following:

  • Nystagmus (horizontal, vertical)
  • Ophthalmoplegia
  • Diplopia
  • Miosis or mydriasis

Phentyoin has been reported to cause DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), a potentially fatal hypersensitivity reaction. Hypersensitivity reactions, including DRESS syndrome, typically manifest after a delay of 2 - 6 wk after exposure and may include the following:

Cardiovascular findings may include the following:

Skin findings may include the following:

Gastrointestinal/abdomen findings may include the following:

  • Right upper quadrant tenderness
  • Hepatomegaly
  • Splenomegaly
  • Nausea
  • Vomiting

Metabolic findings in patients with chronic phenytoin toxicity include osteomalacia and hypothyroidism.

Fetal hydantoin syndrome

Intrauterine exposure to phenytoin may result in the following physical features:

  • Broad nasal bridge
  • Wide fontanelle
  • Low hairline
  • Cleft lip/palate
  • Epicanthal folds
  • Short neck
  • Microcephaly
  • Low-set ears
  • Small or absent nails
  • Hip dislocation
  • Hypoplasia of distal phalanges
  • Impaired growth
  • Congenital heart defects