Phenytoin Toxicity Differential Diagnoses

Updated: Dec 31, 2020
  • Author: Charlene Miller, MD; Chief Editor: David Vearrier, MD, MPH  more...
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DDx

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