Cyclophosphamide and Netupitant: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Netupitant
No brand names on recordCyclophosphamide
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.
What happens
Reduced cyclophosphamide efficacy
Interaction Deep Dive
Caution and monitoring are warranted with coadministration of cyclophosphamide (a CYP3A substrate) and CYP3A inhibitors like netupitant2, because coadministration may decrease the metabolism of cyclophosphamide to the active metabolite 4-hydroxycyclophosphamide, which potentially could decrease cyclophosphamide efficacy 1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated cyclophosphamide metabolism to active metabolite 4-hydroxycyclophosphamide
Literature reports
1 report — tap to read
a) In cancer patients, cyclophosphamide mean Cmax and AUC were 27% and 20% higher, respectively, when coadministered with netupitant/palonosetron than with concurrent use with palonosetron alone 2. Cyclophosphamide is a prodrug and inhibition of its metabolism to the active metabolite 4-hydroxycyclophosphamide may decrease cyclophosphamide efficacy 1.
Common questions
Can I take Cyclophosphamide and Netupitant together?
Reduced cyclophosphamide efficacy Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cyclophosphamide and Netupitant 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.
Questions for your pharmacist
- Does my dose of Cyclophosphamide or Netupitant 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)
- Product Information: CYCLOPHOSPHAMIDE intravenous injection, oral tablets, cyclophosphamide intravenous injection, oral tablets. Baxter Healthcare Corporation (per FDA), Deerfield, IL, 2013. DailyMed
- Product Information: AKYNZEO(R) oral capsules, netupitant palonosetron oral capsules. Eisai Inc (per manufacturer), Woodcliff Lake, NJ, 2014. DailyMed
Keep reading about Netupitant
Keep reading about Cyclophosphamide
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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