Cyclophosphamide Injection and Thiotepa: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cyclophosphamide Injection
Thiotepa
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 conversion to the active metabolite 4-hydroxycyclophosphamide and reduced efficacy of cyclophosphamide
Interaction Deep Dive
In a pharmacokinetic study, CYP2B6 activity was inhibited by 78.1% +/- 0.2% when thiotepa was used with S-mephenytoin (CYP2B6 substrate probe) in human liver microsomes. Use caution during coadministration of cyclophosphamide and thiotepa1. Coadministration of thiotepa (a CYP2B6 inhibitor) and cyclophosphamide (CYP2B6 substrate) reduces the conversion of cyclophosphamide to the active metabolite (4-hydroxycyclophosphamide), the effect appears sequence dependent with a greater reduction in the conversion to 4-hydroxycyclophosphamide when thiotepa is administered 1.5 hours prior to the intravenous administration of cyclophosphamide compared to administration of thiotepa after intravenous cyclophosphamide. The reduction in 4-hydroxycyclophosphamide levels may potentially reduce efficacy of cyclophosphamide treatment 2.
Why it happens (mechanism)
Inhibition of CYP2B6-mediated metabolism of cyclophosphamide (prodrug) to its active metabolite by thiotepa
Literature reports
2 reports — tap to read
a) In a pharmacokinetic study using S-mephenytoin (200 mcmol) as a CYP2B6 substrate probe with thiotepa (50 mcmol) in human liver microsomes, CYP2B6 activity was inhibited by 78.1% +/- 0.2%. Thiotepa in the range of 50 to 100 mcmol inhibited the activity of CYP2B6 by 78% and 83%, respectively, with a plateau effect seen around 50 mcmol 1.
b) The administration of thiotepa 1.5 hours prior to intravenous cyclophosphamide in patients administered cyclophosphamide plus thiotepa plus carboplatin decreased the AUC of 4-hydroxycyclophosphamide by 26% and maximal concentrations of 4-hydroxycyclophosphamide by 62%, compared to administration of cyclophosphamide prior to thiotepa 2.
Common questions
Can I take Cyclophosphamide Injection and Thiotepa together?
Reduced cyclophosphamide conversion to the active metabolite 4-hydroxycyclophosphamide and reduced efficacy of cyclophosphamide Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cyclophosphamide Injection and Thiotepa 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Cyclophosphamide Injection or Thiotepa 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)
- Rae JM, Soukhova NV, Flockhart DA, et al: Triethylenethiophosphoramide is a specific inhibitor of cytochrome P450 2B6: implications for cyclophosphamide metabolism. Drug Metab Dispos 2002; 30(5):525-530. DOI
- Product Information: TEPYLUTE intravenous injection, thiotepa intravenous injection. Shorla Oncology Inc (per FDA), Cambridge, MA, 2024. DailyMed
Keep reading about Cyclophosphamide Injection
Keep reading about Thiotepa
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