Relugolix and Phenytoin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenytoin
Relugolix
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.
Here's what's going on. Phenytoin (Dilantin) is a strong "speed-up" drug. It revs up the body systems that break down and pump out relugolix (Orgovyx). When those systems run faster, your body clears relugolix quicker, so less of it stays in your blood. That means relugolix may not work as well as it should.
This matters because relugolix is doing an important job, and you want it fully effective. The good news is your care team can handle this. Please don't change anything on your own. Just let your pharmacist or doctor know you take both, and they can adjust the plan to keep your treatment working.
Effect: Phenytoin, a combined P-gp and strong CYP3A inducer, is expected to reduce relugolix exposure and efficacy. Relugolix is a P-gp and CYP3A substrate (not a prodrug), so induction lowers its levels.
- Mechanism: Induction of P-gp efflux and CYP3A metabolism of relugolix.
- Magnitude: Extrapolated from rifampin data (relugolix AUC decreased 55%, Cmax 23%).
- Evidence: Theoretical for phenytoin specifically; onset unspecified.
- Management: Avoid the combination if possible. If unavoidable, increase relugolix to 240 mg once daily; resume 120 mg once daily after the inducer is discontinued. Monitor for reduced therapeutic response.
What happens
Reduced relugolix exposure and reduced efficacy of relugolix
Interaction Deep Dive
When relugolix (a substrate of both P-gp and CYP3A) is given together with an agent that induces both P-gp and CYP3A strongly, relugolix exposure declines, which can lessen how well it works. For this reason, do not combine relugolix, or the relugolix/estradiol/norethindrone acetate product, with a combined P-gp and strong CYP3A inducer12. In studies, giving relugolix alongside rifAMPin (an inducer of P-gp and a strong CYP3A inducer) lowered relugolix AUC by 55% and Cmax by 23%. Should such coadministration be unavoidable, the relugolix dose should be raised to 240 mg once daily. Once the combined P-gp and strong CYP3A inducer has been stopped, return to the standard relugolix dose of 120 mg once daily1.
Why it happens (mechanism)
Induction of P-gp-mediated efflux transport of relugolix; induction of CYP3A-mediated metabolism of relugolix
How to manage this interaction
What your care team may do:
- Where possible, they may avoid using these two together, or choose a different option.
- If you do need both, the relugolix dose may be adjusted (guidance supports increasing to 240 mg once daily while on phenytoin).
- Once phenytoin is stopped, the usual relugolix dose (120 mg once daily) is typically resumed.
- They may monitor you more closely to be sure relugolix is still working.
What you should do: Keep taking both exactly as prescribed, and don't change doses yourself. Tell your pharmacist or prescriber that you take both so they can tailor the plan for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) When relugolix (a substrate of P-gp and CYP3A) was given together with rifAMPin (an inducer of P-gp and a strong CYP3A inducer), the AUC and Cmax of relugolix fell by 55% and 23%, respectively 1.
Common questions
Can I take Relugolix and Phenytoin together?
Phenytoin can lower relugolix levels and make it less effective; keep taking both as prescribed and check with your pharmacist or doctor, who can adjust the relugolix dose or choose another option. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Phenytoin 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 is the Relugolix and Phenytoin interaction managed?
What your care team may do: Where possible, they may avoid using these two together, or choose a different option. If you do need both, the relugolix dose may be adjusted (guidance supports increasing to 240 mg once daily while on phenytoin). Once phenytoin is stopped, the usual relugolix dose (120 mg once daily) is typically resumed. They may monitor you more closely to be sure relugolix is still… Management is individual — always follow your own care team's guidance.
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 Relugolix or Phenytoin 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 (2)
- Product Information: ORGOVYX oral tablets, relugolix oral tablets. Sumitomo Pharma America, Inc (per FDA), Marlborough, MA, 2025. DailyMed
- Product Information: MYFEMBREE(R) oral tablets, relugolix, estradiol, norethindrone acetate oral tablets. Myovant Sciences Inc (per FDA), Brisbane, CA, 2021. DailyMed
Keep reading about Phenytoin
Keep reading about Relugolix
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