Relugolix and Apalutamide: 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
Apalutamide
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 the key thing to know. Apalutamide (Erleada) can speed up how your body breaks down and pushes out relugolix (Orgovyx). That means less relugolix stays in your system, so it may not work as well as it should. Since relugolix is often used to help control prostate cancer, weaker effect is a real concern.
The good news is that your care team can manage this. In some cases they may avoid using the two together, and if both are truly needed, they can adjust your relugolix dose. Please don't change anything on your own. Just let your doctor or pharmacist know you're taking both so they can plan the safest approach for you.
Effect: Apalutamide, a combined P-gp and strong CYP3A inducer, reduces relugolix exposure and may compromise efficacy. Relugolix is a P-gp and CYP3A4 substrate (not a prodrug), so induction lowers its plasma levels.
- Direction: reduced relugolix AUC/Cmax, potential loss of androgen suppression.
- Magnitude: with rifampin (comparator inducer), relugolix AUC decreased 55% and Cmax 23%.
- Evidence: theoretical (extrapolated from rifampin data); severity rated major.
- Management: avoid the combination. If unavoidable, increase relugolix to 240 mg once daily during coadministration; resume 120 mg once daily after the inducer is discontinued.
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 falls, potentially diminishing its effectiveness. For this reason, relugolix or the relugolix/estradiol/norethindrone acetate combination should not be used alongside a combined P-gp and strong CYP3A inducer12. In a case involving rifAMPin (an inducer of P-gp and a strong inducer of CYP3A), concurrent use lowered relugolix AUC by 55% and Cmax by 23%. Should such combined use prove necessary, the relugolix dose should be raised to 240 mg taken once each day. Once the combined P-gp and strong CYP3A inducer is stopped, the standard relugolix regimen of 120 mg once daily should be resumed1.
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:
- Try to avoid using apalutamide together with relugolix (or relugolix/estradiol/norethindrone acetate) when possible.
- If both are truly needed, your prescriber may increase your relugolix dose while you are on apalutamide, then return it to the usual dose after apalutamide is stopped.
- Monitor you more closely to confirm relugolix is still working.
What you should do: Keep taking both exactly as prescribed and do not adjust doses yourself. Tell your pharmacist or doctor that you take both so they can tailor your relugolix dose and follow-up.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) When relugolix (a substrate of both P-gp and CYP3A) was given together with rifAMPin (a P-gp and strong CYP3A inducer), the AUC and Cmax of relugolix were reduced by 55% and 23%, respectively 1.
Common questions
Can I take Relugolix and Apalutamide together?
Apalutamide can lower relugolix levels and may weaken its effect; don't stop either drug on your own, but make sure your care team knows you take both so they can adjust the relugolix dose or choose an alternative. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Apalutamide 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 Apalutamide interaction managed?
What your care team may do: Try to avoid using apalutamide together with relugolix (or relugolix/estradiol/norethindrone acetate) when possible. If both are truly needed, your prescriber may increase your relugolix dose while you are on apalutamide, then return it to the usual dose after apalutamide is stopped. Monitor you more closely to confirm relugolix is still working. What you should do: Kee… 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 Apalutamide 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 Apalutamide
Keep reading about Relugolix
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