Relugolix and Enzalutamide: 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
Enzalutamide
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.
These two prostate cancer medicines can interact. Relugolix (Orgovyx) is normally pushed out of your body by a kind of cellular "pump" called P-gp. Enzalutamide (Xtandi) can slow that pump down, which means more relugolix can build up in your body than expected. Higher levels can mean a higher chance of relugolix side effects.
The good news is your care team knows how to handle this. They may space the two doses apart, watch you more closely for side effects, or adjust your plan. Please don't stop or change either medicine on your own. Just check in with your pharmacist or doctor so they can keep you safe.
Effect: Increased relugolix exposure via inhibition of P-gp-mediated efflux (relugolix is a P-gp substrate; enzalutamide inhibits intestinal P-gp). Neither drug's active effect depends on prodrug activation here.
Magnitude: The labeled P-gp inhibitor probe (erythromycin) raised relugolix AUC ~3.5-fold and Cmax ~2.9-fold. Evidence: probable. Severity: major.
- Preferred: Avoid concomitant use when possible.
- If unavoidable: Give relugolix first, separate dosing by at least 6 hours, and increase monitoring for relugolix adverse reactions.
- Relugolix may be interrupted up to 2 weeks for short P-gp inhibitor courses; if held >7 days, resume with 360 mg loading dose then 120 mg daily.
What happens
Increased relugolix exposure
Interaction Deep Dive
Concurrent administration of relugolix (a P-gp substrate) with P-gp inhibitors should be avoided, since doing so may raise relugolix exposure and thereby heighten the likelihood of relugolix-related adverse reactions. When coadministration cannot be avoided, give relugolix or relugolix/estradiol/norethindrone acetate first, keep the doses at least 6 hours apart, and increase the frequency of monitoring for adverse reactions12. Relugolix therapy may be paused for as long as 2 weeks to permit a brief course of certain P-gp inhibitors, with relugolix resumed once the P-gp inhibitor has been stopped. Should relugolix be interrupted for more than 7 days, it should be reinitiated with a 360 mg loading dose on the first day, followed by 120 mg once daily thereafter. A drug interaction study showed that giving relugolix (P-gp substrate) together with erythromycin (P-gp inhibitor) raised relugolix AUC by 3.5-fold and Cmax by 2.9-fold1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of relugolix
How to manage this interaction
What your care team may do:
- Try to avoid using the two together when there is an option.
- If both are needed, take relugolix first and separate the doses by at least 6 hours.
- Watch you more closely for relugolix side effects.
- In some cases pause relugolix for a short course of the other drug, then restart it (your team will decide on any loading dose).
What you should do: Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Ask your pharmacist or doctor how to time your doses and what side effects to watch for. Your dose and monitoring can be individualized by your care team.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A drug interaction study showed that giving relugolix (a P-gp substrate) together with erythromycin (a P-gp inhibitor) raised the AUC and Cmax of relugolix by 3.5-fold and 2.9-fold, respectively 1.
Common questions
Can I take Relugolix and Enzalutamide together?
Enzalutamide can raise relugolix levels and side-effect risk by blocking a drug-transport pump, so ask your care team about spacing doses and closer monitoring. Do not stop or change either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Enzalutamide 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 Enzalutamide interaction managed?
What your care team may do: Try to avoid using the two together when there is an option. If both are needed, take relugolix first and separate the doses by at least 6 hours. Watch you more closely for relugolix side effects. In some cases pause relugolix for a short course of the other drug, then restart it (your team will decide on any loading dose). What you should do: Keep taking both exactly a… Management is individual — always follow your own care team's guidance.
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 Relugolix or Enzalutamide 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 Enzalutamide
Keep reading about Relugolix
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