Drug Interaction Report

Cyclophosphamide and Fluconazole: Interaction Details

A pharmacist-reviewed analysis of the Cyclophosphamide 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
+

Cyclophosphamide

Cytoxan® Frindovyx
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
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 88 documented Cyclophosphamide interactions, 31 are rated moderate — including this one.
Onset
unspecified
Evidence
theoretical
Severity
Moderate

What happens

Reduced activation of cycloPHOSphamide to 4-hydroxycycloPHOSphamide and a risk of increased serum bilirubin and creatinine

Interaction Deep Dive

Coadministration of cycloPHOSphamide together with fluconazole may result in increased serum bilirubin and serum creatinine. Additionally, fluconazole-mediated CYP2C9 and CYP3A4 inhibition2 may decrease activation of cycloPHOSphamide to 4-hydroxycycloPHOSphamide, which may potentially decrease cycloPHOSphamide efficacy. However, activation of cycloPHOSphamide is mediated by other CYP450 isoenzymes, including CYP2A6, 2B6, 3A5, 2C18, and 2C19, with 2B6 exhibiting the most 4 hydroxylase activity 1. Fluconazole-mediated CYP3A4 inhibition may continue for 4 to 5 days after discontinuation because of the long half-life 2.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated activation of cycloPHOSphamide by fluconazole

Common questions

Can I take Cyclophosphamide and Fluconazole together?

Reduced activation of cycloPHOSphamide to 4-hydroxycycloPHOSphamide and a risk of increased serum bilirubin and creatinine Always confirm with your pharmacist or prescriber before making any change.

How serious is the Cyclophosphamide and Fluconazole interaction?

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

From our Q&A

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

Questions for your pharmacist

  • Does my dose of Cyclophosphamide 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 anything you'd monitor while I'm on both?

References (2)

  1. Product Information: CYCLOPHOSPHAMIDE intravenous injection, oral tablets, cyclophosphamide intravenous injection, oral tablets. Baxter Healthcare Corporation (per FDA), Deerfield, IL, 2013. DailyMed
  2. Product Information: DIFLUCAN(R) oral tablets, suspension, fluconazole oral tablets, suspension. Roerig (per FDA), New York, NY, 2023. DailyMed
Was this write-up helpful?
Fluconazole

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

Keep reading about Cyclophosphamide

All Cyclophosphamide interactions (88) Cyclophosphamide drug information
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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:

Fluconazole + Activated Charcoal Beer Siberian Cocklebur Wine Adrafinil Ashwagandha Black Cohosh Boldo + 73 more
Cyclophosphamide + Activated Charcoal Beer Grapefruit Siberian Cocklebur St. John's Wort Wine Acacia Rigidula Acerola + 212 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.