eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Phenytoin: Differential Diagnoses & Workup

Author: Charlene A Miller, MD, Consulting Staff, Department of Emergency Medicine, Oakwood Hospital Medical Center
Coauthor(s): Daniel M Joyce, MD, Consulting Staff, Department of Emergency Medicine, Saint Vincent's and Saint Mary's Medical
Contributor Information and Disclosures

Updated: Jul 15, 2009

Differential Diagnoses

Alcohol and Substance Abuse Evaluation
Toxicity, Barbiturate
Encephalitis
Toxicity, Benzodiazepine
Erythema Multiforme
Toxicity, Carbamazepine
Hepatitis
Toxicity, Isoniazid
Hypoglycemia
Toxicity, Sedative-Hypnotics
Shock, Cardiogenic
Toxicity, Valproate
Stevens-Johnson Syndrome
Systemic Lupus Erythematosus
Toxic Epidermal Necrolysis

Workup

Laboratory Studies

  • 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.
  • Aspirin and acetaminophen levels
  • Perform pregnancy tests in women of childbearing age.
  • 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.
  • 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.

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

Other Tests

  • Electrocardiogram
    • 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.

More on Toxicity, Phenytoin

Overview: Toxicity, Phenytoin
Differential Diagnoses & Workup: Toxicity, Phenytoin
Treatment & Medication: Toxicity, Phenytoin
Follow-up: Toxicity, Phenytoin
References
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References

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Further Reading

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Keywords

phenytoin toxicity, phenytoin poisoning, phenytoin exposure, anticonvulsant drug, seizure disorder, phenytoin overdose, elevated phenytoin levels, status epilepticus, phenytoin ingestion, seizure treatment, treatment of seizure

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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.

Medical Editor

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.

Pharmacy Editor

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.

Managing Editor

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.

CME Editor

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, Department of Surgery, Section 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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