Phenytoin Toxicity Clinical Presentation

Updated: Dec 05, 2018
  • 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



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:

  • Hypotension, bradycardia [6] , myocardial depression, ventricular fibrillation, asystole, and tissue necrosis [7] all have been associated with the IV formulation.

  • Phlebitis, necrosis, even gangrene

  • "Purple glove syndrome," comprising distal limb edema, discoloration, and pain after IV administration, usually occurs in elderly patients and after massive/multiple doses

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