Drug Interaction Report

Azithromycin and Fluconazole: Interaction Details

A pharmacist-reviewed analysis of the Azithromycin 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 Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Fluconazole

Diflucan
+

Azithromycin

AzaSite Zithromax Zithromax® Zithromax® Single Dose Packets Zithromax® Tri-Paks® Zithromax® Z-Paks® Zmax®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Jul 11, 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 299 documented Azithromycin interactions, 264 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
theoretical
Severity
Major

What happens

An increased risk of QT interval prolongation

Interaction Deep Dive

Consider the risk of QT prolongation which can be fatal when initiating azithromycin in patients taking drugs that may prolong the QT interval12 like fluconazole, as this may result in additive effects on QT interval prolongation and an increased risk of serious cardiovascular effects, including torsade de pointes 34.

Why it happens (mechanism)

Additive QT interval prolongation

Literature reports

1 report — tap to read

a) Case reports have described QT prolongation and torsades de points associated with fluconazole 56.

Common questions

Can I take Azithromycin and Fluconazole together?

An increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.

How serious is the Azithromycin 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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

  • Does my dose of Azithromycin 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 (6)

  1. Product Information: ZMAX(R) oral extended-release suspension, azithromycin oral extended-release suspension. Pfizer Inc (per FDA), New York, NY, 2021. DailyMed
  2. Product Information: ZITHROMAX(R) oral tablets, oral suspension, azithromycin oral tablets, oral suspension. Pfizer Labs (per FDA), New York, NY, 2017. DailyMed
  3. Product Information: DIFLUCAN(R) oral tablets, suspension, fluconazole oral tablets, suspension. Roerig (per FDA), New York, NY, 2024. DailyMed
  4. Product Information: DIFLUCAN(R) intravenous injection, fluconazole intravenous injection. Roerig (per FDA), New York, NY, 2024. DailyMed
  5. Khazan M & Mathis AS: Probable cause of torsades de pointes induced by fluconazole. Pharmacotherapy 2002; 22(12):1632-1637.
  6. Wassmann S, Nickenig G, & Bohm M: Long QT syndrome and torsade de pointes in a patient receiving fluconazole. Ann Intern Med 1999; 131:797. PubMed
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Fluconazole

Keep reading about Fluconazole

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

Keep reading about Azithromycin

All Azithromycin interactions (299) Azithromycin drug information
Also serious with: Pimozide Mesoridazine Levoketoconazole Colchicine
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
Azithromycin + Activated Charcoal American Hellebore Arsenic Cesium Ephedra Grapefruit Oleander Sida Cordifolia + 84 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.