Drug Interaction Report

Ibuprofen and Fluconazole: Interaction Details

A pharmacist-reviewed analysis of the Ibuprofen and Fluconazole interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

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

Fluconazole

Diflucan
+

Ibuprofen

Addaprin Addaprin® Advil Caldolor Cedaprin® Counteract IB dvil® Genpril
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close 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 302 documented Ibuprofen interactions, 235 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
probable
Severity
Major

What happens

Increased NSAIDs exposure and an increased risk of NSAIDs-related adverse reactions

Interaction Deep Dive

Exert caution when fluconazole is coadministered with certain NSAIDs that are metabolized by CYP2C9 (e.g., ibuprofen, naproxen, lornoxicam, meloxicam, diclofenac) as it may increase the systemic exposure of these NSAIDs. The Cmax and AUC of flurbiprofen were increased by 23% and 81%, respectively, when coadministered with fluconazole compared to administration of flurbiprofen alone. Similarly, the Cmax and AUC of the pharmacologically active isomer [S-(+)-ibuprofen] were increased by 15% and 82%, respectively, when fluconazole was coadministered with racemic ibuprofen (400 mg) compared to administration of racemic ibuprofen alone. Frequent monitoring for adverse events and toxicity related to NSAIDs is recommended. Adjustment of dosage of NSAIDs may be needed. The enzyme inhibiting effect of fluconazole persists 4 to 5 days after discontinuation of fluconazole treatment due to the long half-life of fluconazole12.

Why it happens (mechanism)

Inhibition of CYP2C9-mediated metabolism by fluconazole

Literature reports

1 report — tap to read

a) The Cmax and AUC of flurbiprofen were increased by 23% and 81%, respectively, when coadministered with fluconazole compared to administration of flurbiprofen alone. Similarly, the Cmax and AUC of the pharmacologically active isomer [S-(+)-ibuprofen] were increased by 15% and 82%, respectively, when fluconazole was coadministered with racemic ibuprofen (400 mg) compared to administration of racemic ibuprofen alone 12.

Common questions

Can I take Ibuprofen and Fluconazole together?

Increased NSAIDs exposure and an increased risk of NSAIDs-related adverse reactions Always confirm with your pharmacist or prescriber before making any change.

How serious is the Ibuprofen and Fluconazole interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

How strong is the evidence for this interaction?

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

Questions for your pharmacist

  • Does my dose of Ibuprofen or Fluconazole 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 a safer alternative to one of these medications for me?

References (2)

  1. Product Information: DIFLUCAN(R) intravenous injection, fluconazole intravenous injection. Roerig (per FDA), New York, NY, 2024. DailyMed
  2. Product Information: DIFLUCAN(R) oral tablets, suspension, fluconazole oral tablets, suspension. Roerig (per FDA), New York, NY, 2024. DailyMed
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Fluconazole

Keep reading about Fluconazole

All Fluconazole interactions (166)
Also serious with: Buprenorphine Glasdegib Bedaquiline Sertraline
Ibuprofen

Keep reading about Ibuprofen

All Ibuprofen interactions (302) Ibuprofen drug information
Also serious with: Ketorolac Ophthalmic Ketorolac Injection Ketorolac Nasal Spray Ketorolac
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:

Fluconazole + Activated Charcoal Beer Siberian Cocklebur Wine Adrafinil Ashwagandha Black Cohosh Boldo + 73 more
Ibuprofen + Activated Charcoal Asarabacca Beer Danshen Piracetam Siberian Cocklebur Wine Aconite + 278 more

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.