Drug Interaction Report

Fluconazole and Nicardipine: Interaction Details

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Fluconazole

Diflucan
+

Nicardipine

Cardene Cardene® Cardene® SR
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Aug 8, 2026
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Interaction severity
Moderate
Can be significant — usually manageable with monitoring.
How we grade severity & evidence

Severity levels

  • Contraindicated: These should generally not be used together.
  • Major: Potentially serious — often needs a change or close monitoring.
  • Moderate: Can be significant — usually manageable with monitoring.
  • Minor: Usually limited clinical impact.

Evidence grades

  • Established: Well documented — supported by controlled studies or strong clinical data.
  • Probable: Good supporting evidence, though not definitively proven.
  • Suspected: Some evidence suggests this interaction, but it is not well established.
  • Possible: Limited or conflicting evidence; the interaction may occur.
  • Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.

Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.

Of 166 documented Fluconazole interactions, 22 are rated moderate — including this one.
Onset
delayed
Evidence
probable
Severity
Moderate

What happens

Increased niCARdipine serum concentrations and toxicity (dizziness, hypotension, flushing, headache, peripheral edema)

Interaction Deep Dive

Triazole antifungals (itraconazole, fluconazole) and imidazole antifungals (ketoconazole) inhibit hepatic isoenzyme CYP3A4, an enzyme involved in the metabolism of dihydropyridine calcium channel antagonists (nifedipine, niCARdipine, amlodipine, isradipine, felodipine)3. Literature reports have documented substantial peripheral edema and/or elevated calcium antagonist serum concentrations during concurrent use of itraconazole and felodipine, isradipine, or nifedipine 24. Since the other triazole and imidazole antifungals also inhibit CYP3A4, this interaction would be expected to occur with other combinations.

Why it happens (mechanism)

Inhibition of hepatic isoenzyme CYP3A4 resulting in decreased metabolism of the dihydropyridine calcium channel antagonist

Literature reports

2 reports — tap to read

a) A case report of a 68-year-old woman taking nifedipine and atenolol for hypertension was started on itraconazole for pedal onychomycosis reported ankle edema. She apparently had never had ankle edema before. The ankle edema appeared after two to three days of itraconazole and resolved two to three days after itraconazole was discontinued. The ankle edema reappeared with each subsequent course of itraconazole except the final course. Nifedipine trough concentrations were obtained with the last course of therapy. Relative to the itraconazole therapy trough nifedipine trough concentrations were obtained on 4 days prior to and three days during therapy. The mean nifedipine trough concentration prior to therapy was 12.7 nanogram/mL (ng/mL; 36.7 nanomol/L) and 56.1 ng/mL (162 nanomol/L) during itraconazole therapy 1.

b) Peripheral edema and elevated serum felodipine levels were described in two patients receiving combined therapy with felodipine and itraconazole. Swelling of the lower extremities occurred in both cases within 3-7 days and resolved within 2-4 days following discontinuation of one of the agents. Re-challenge in one of the patients resulted in reoccurrence of the edema. In this patient, area under the felodipine plasma concentration-time curve (AUC) was found to be at least four times higher with itraconazole therapy 2. The authors also mention an additional patient who developed ankle swelling when itraconazole was added to isradipine therapy, however, further details were not supplied.

Common questions

Can I take Fluconazole and Nicardipine together?

Increased niCARdipine serum concentrations and toxicity (dizziness, hypotension, flushing, headache, peripheral edema) Always confirm with your pharmacist or prescriber before making any change.

How serious is the Fluconazole and Nicardipine interaction?

It is rated moderate. Can be significant — usually manageable with monitoring.

How quickly could this interaction happen?

The documented onset is "delayed". Effects tend to build up gradually over days to weeks.

How strong is the evidence for this interaction?

The evidence is graded "probable". Good supporting evidence, though not definitively proven.

From our Q&A

Real reader questions about these medications, each personally answered by our pharmacist:

Questions for your pharmacist

  • Does my dose of Fluconazole or Nicardipine need adjusting while I take them together?
  • What symptoms should prompt me to call you or my prescriber right away?
  • Does the timing of my doses matter for this combination?
  • Is there anything you'd monitor while I'm on both?

References (4)

  1. Tailor S, Gupta A, Walker S, et al: Peripheral edema due to nifedipine-itraconazole interaction: a case report. Arch Dermatol 1996; 132:350-352. DOI
  2. Neuvonen PJ & Suhonen R: Itraconazole interacts with felodipine. J Am Acad Dermatol 1995; 33:134-135. PubMed
  3. Gibaldi M: Drug interactions: part I. Ann Pharmacother 1992; 26:709-713. DOI
  4. Tailor S, Gupta A, Walker S, et al: Peripheral edema due to nifedipine-itraconazole interaction: a case report. Arch Dermatol 1996; 132:350-352. DOI
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Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.