Entacapone and Cyclophosphamide: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Entacapone
Cyclophosphamide
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
Decreased activation of cyclophosphamide to 4-hydroxycyclophosphamide and risk for increased serum bilirubin and creatinine
Interaction Deep Dive
Caution is advised when using cyclophosphamide together with entacapone as concomitant use may decrease activation of cyclophosphamide to 4-hydroxycyclophosphamide, which may increase serum bilirubin and creatinine and 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 activity1.
Why it happens (mechanism)
Inhibition of CYP2C9-mediated activation of cyclophosphamide by entacapone
Common questions
Can I take Entacapone and Cyclophosphamide together?
Decreased activation of cyclophosphamide to 4-hydroxycyclophosphamide and risk for increased serum bilirubin and creatinine Always confirm with your pharmacist or prescriber before making any change.
How serious is the Entacapone and Cyclophosphamide 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 Entacapone or Cyclophosphamide 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 (1)
- Product Information: CYCLOPHOSPHAMIDE intravenous injection, oral tablets, cyclophosphamide intravenous injection, oral tablets. Baxter Healthcare Corporation (per FDA), Deerfield, IL, 2013. DailyMed
Keep reading about Entacapone
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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