Phenytoin and Darolutamide: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenytoin
Darolutamide
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 darolutamide exposure
Interaction Deep Dive
Darolutamide is primarily metabolized by CYP3A4 and is also a P-gp substrate. Avoid concomitant use of darolutamide with drugs known to be combined P-gp and strong or moderate CYP3A4 inducers, as coadministration may result in decreased darolutamide exposure, which may lead to loss of therapeutic effect In a pharmacokinetic study, coadministration with rifampin (a combined P-gp and strong CYP3A4 inducer) decreased mean darolutamide AUC by 72% and Cmax by 52%1.
Why it happens (mechanism)
Induction of P-gp-mediated darolutamide efflux transport and CYP3A4-mediated darolutamide metabolism
Literature reports
1 report — tap to read
a) In a pharmacokinetic trial, coadministration of darolutamide with rifampin (combined P-gp and strong CYP3A4 inducer) decreased mean darolutamide AUC(0 to 72) by 72% and Cmax by 52%. Coadministration with a moderate CYP3A4 inducer is projected to reduce darolutamide exposure by 36% to 58% 1.
Common questions
Can I take Phenytoin and Darolutamide together?
Decreased darolutamide exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Phenytoin and Darolutamide 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 Phenytoin or Darolutamide 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 (1)
- Product Information: NUBEQA(R) oral tablets, darolutamide oral tablets. Bayer HealthCare Pharmaceuticals Inc (per manufacturer), Whippany, NJ, 2019. DailyMed
Keep reading about Phenytoin
Keep reading about Darolutamide
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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