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Phenytoin Toxicity Differential Diagnoses

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

Diagnostic Considerations

Drug interactions are an important consideration in patients who are taking other medications in combination with phenytoin. Numerous interactions between phenytoin and other medications are known to exist, and can result in inadvertent toxicity or decreased efficacy.

Phenytoin increases serum levels of toxic metabolites of the following:

  • Acetaminophen
  • Oral anticoagulants
  • Primidone (eg, phenobarbital)

Phenytoin decreases serum levels of the following:

  • Amiodarone
  • Carbamazepine
  • Oral contraceptives
  • Corticosteroids
  • Cyclosporine
  • Disopyramide
  • Doxycycline
  • Furosemide
  • Levodopa
  • Methadone
  • Mexiletine
  • Quinidine
  • Theophylline
  • Valproic acid

Serum levels of phenytoin are increased by the following:

  • Amiodarone
  • Chloramphenicol
  • Cimetidine
  • Disulfiram
  • Ethosuximide
  • Fluconazole
  • Isoniazid
  • Oral anticoagulants
  • Phenylbutazone (long banned in the United States and other countries, but still available in some Latin American countries)
  • Sulfonamides
  • Trimethoprim
  • Valproic acid

Serum levels of phenytoin are decreased by the following:

  • Antineoplastic drugs
  • Calcium
  • Diazepam
  • Diazoxide
  • Ethanol (long-term use),
  • Folic acid
  • Phenobarbital
  • Rifampin
  • Sucralfate
  • Theophylline

Differential Diagnoses

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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