Drug Interaction: Dilantin and Diflucan

64 year old female with a history of seizures, hypertension, and osteoarthritis was diagnosed with a case of recurrent vaginal candidiasis.  Her current medications included:

  • Dilantin
  • Enalapril
  • Amlodipine
  • Ibuprofen as needed

Her previous labs were unremarkable with a total Dilantin (phenytoin) level of 16 and seizure free for well over a period of a year.  She had not been experiencing any signs of toxicity as well.

For treatment of the candidiasis, she was prescribed Diflucan (fluconazole) for a period of 14 days.  Approximately halfway through the treatment period, family was concerned with a change in mentation in the patient.  She had also had a fall and was having trouble walking.  Family was questioning if the patient was having side effects from the newly prescribed Diflucan.

Upon investigation, a Dilantin level was checked, and revealed to be 27.  She was diagnosed with Dilantin toxicity.

When I think of fluconazole, I normally think of all the classic CYP3A4 interactions.  Per Lexicomp, Dilantin and Diflucan interaction is likely caused by fluconazole’s ability to inhibit CYP2C19.

A huge thank you to all of you who helped make this Ebook the #1 Amazon Best Seller in both Pharmacy and Pharmacology!  –  Something I certainly didn’t see coming!

Eric Christianson, PharmD, BCPS, CGP


  1. gk

    Congrats on the book, a pdf version would make it a whole lot more widely read ~ just sayin 🙂

  2. yawen

    I’m considering if the situation happens, what can e suggest? Switch to another anti-seizure medications or titrate the dose of phenytoin? In my own experience, the physician and I prefer switch to valproic acid in substitute.

  3. Mohammed Musawa

    What about amlodipine and Phenytoin ?
    Per Lexicomp there category D drug interaction!!



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Written By Eric Christianson

March 15, 2015

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