Toxicity, Phenytoin Workup

  • Author: Charlene A Miller, MD; Chief Editor: Asim Tarabar, MD   more...
 
Updated: Nov 4, 2010
 

Laboratory Studies

Obtain a serum phenytoin level. The therapeutic range is 10-20 mcg/mL. Plasma levels (mcg/mL) have an association with acute neurological symptoms. Free phenytoin levels range from 1-2 mcg/mL and correlate well with clinical evidence of toxicity (ie, individuals with decreased protein binding may have signs and symptoms of toxicity despite a normal total phenytoin level; however, their free phenytoin level is elevated):

  • 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

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

Obtain aspirin and acetaminophen levels.

Perform pregnancy tests in women of childbearing age.

For acute toxicity:

  • 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.
  • Perform liver function tests for suspected hepatotoxicity or to determine patient's baseline.

For chronic toxicity:

  • Obtain a complete blood count (CBC) to rule out anemia, eosinophilia, atypical lymphocytosis, and pancytopenia.
  • Perform liver function tests (LFTs) to rule out hepatotoxicity.
  • Measure electrolytes to rule out hyperglycemia and hyperosmolar nonketotic coma.

Drug interactions: If prescribing other medications in combination with phenytoin, be very alert to the possibility of inadvertent toxicity or decreased efficacy of the antiepileptic medication. Numerous interactions between phenytoin and other medications are known to exist.

Phenytoin increases serum levels of toxic metabolites of acetaminophen, oral anticoagulants, and primidone (eg, phenobarbital).

Phenytoin decreases serum levels of amiodarone, carbamazepine, contraceptives, corticosteroids, cyclosporine, disopyramide, doxycycline, furosemide, levodopa, methadone, mexiletine, quinidine, theophylline, and valproic acid.

Serum levels are increased by amiodarone, chloramphenicol, cimetidine, disulfiram, ethosuximide, fluconazole, isoniazid, oral anticoagulants, phenylbutazone, sulfonamides, trimethoprim, and valproic acid.

Serum levels are decreased by antineoplastic drugs, calcium, diazepam, diazoxide, ethanol (chronic), folic acid, phenobarbital, rifampin, sucralfate, and theophylline.

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Imaging Studies

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

Evaluate patient with the history of ataxia and consequent fall(s) for any traumatic injury

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Other Tests

Electrocardiography

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

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

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

Disclosure: Nothing to disclose.

Coauthor(s)

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

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

Disclosure: Nothing to disclose.

Specialty Editor Board

Lance W Kreplick, MD, MMM, FAAEM, FACEP  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, MMM, FAAEM, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physician Executives

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD  Regional Director of Pharmacy, Sacred Heart & 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  Chair, Department of Emergency Medicine, Director of Medical Toxicology, Allegheny General Hospital; Associate Professor, Department of Emergency Medicine, Drexel University College of Medicine

Disclosure: Nothing to disclose.

John D Halamka, MD, MS  Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center

John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

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.

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