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Phenytoin Toxicity Clinical Presentation

  • Author: Charlene Miller, MD; Chief Editor: Asim Tarabar, MD  more...
Updated: Apr 25, 2016


Establish if 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


See the list below:

  • Phenytoin may cause a febrile reaction, hypotension (during intravenous infusion), or bradycardia.
  • Mouth -Gingival hyperplasia is the most common adverse effect (20%) with long-term use
  • Neurologic
    • Hyperreflexia or hyporeflexia
    • Abnormal gait (bradykinesia, truncal ataxia - Ataxia is very typical with elevated phenytoin levels, and may lead to falls and consequent trauma
    • Respiratory distress
    • 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)
  • Eyes
    • Nystagmus (horizontal, vertical)
    • Ophthalmoplegia
    • Diplopia
    • Miosis or mydriasis
  • Hypersensitivity reactions (usually 1-4 wk after exposure)
  • Cardiovascular
    • 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"
      • Distal limb edema, discoloration, and pain after IV administration
      • Usually in elderly and after massive/multiple doses
  • Skin
  • GI/abdomen
    • Right upper quadrant tenderness
    • Hepatomegaly
    • Splenomegaly
    • Nausea
    • Vomiting
    • Hepatitis
  • Metabolic - Osteomalacia and hypothyroidism may result from chronic toxicity

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
Contributor Information and Disclosures

Charlene Miller, MD Consulting Staff, Department of Emergency Medicine, Oakwood Hospital Medical Center

Charlene Miller, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.


Daniel M Joyce, MD Consulting Staff, Department of Emergency Medicine, Saint Vincent's and Saint Mary's Medical Center

Daniel M Joyce, MD is a member of the following medical societies: American College of Emergency Physicians, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Fred Harchelroad, MD, FACMT, FAAEM, FACEP Attending Physician in Emergency Medicine, Excela Health System

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Lance W Kreplick, MD, FAAEM, MMM Medical Director of Hyperbaric Medicine, Fawcett Wound Management and Hyperbaric Medicine; Consulting Staff in Occupational Health and Rehabilitation, Company Care Occupational Health Services; President and Chief Executive Officer, QED Medical Solutions, LLC

Lance W Kreplick, MD, FAAEM, MMM is a member of the following medical societies: American Academy of Emergency Medicine, American Association for Physician Leadership

Disclosure: Nothing to disclose.

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