Relugolix and Rifampin: 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
Rifampin
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.
Rifampin and Orgovyx (relugolix) can push against each other. Relugolix is the medicine that lowers testosterone to treat prostate cancer. When taken by mouth, rifampin can act two ways on relugolix. In some cases it can raise relugolix levels and make side effects more likely. Over longer use, rifampin mostly speeds up how fast your body clears relugolix, which can make it work less well.
The good news is that your care team knows how to handle this. They may adjust your relugolix dose, space the two medicines apart, or watch you more closely. Please don't change or stop anything on your own. Talk with your pharmacist or doctor so they can tailor the plan for you.
Effect: Rifampin alters relugolix exposure. As an oral P-gp inhibitor it can increase relugolix AUC/Cmax (higher adverse-reaction risk), while as a combined P-gp and strong CYP3A inducer it can reduce relugolix exposure and efficacy. Neither is a prodrug. Evidence is probable; severity major.
- Avoid coadministration where possible.
- If P-gp inhibition dominates and use is unavoidable: give relugolix first, separate by at least 6 hours, monitor for adverse reactions.
- Relugolix may be interrupted up to 2 weeks for short P-gp inhibitor courses; if held >7 days, restart with 360 mg loading dose, then 120 mg daily.
- For inducer-dominant exposure loss: increase relugolix to 240 mg once daily.
What happens
Altered relugolix exposure, an increased risk of relugolix-related adverse reactions and reduced efficacy of relugolix
Interaction Deep Dive
Do not give relugolix together with rifAMPin (an oral P-gp inhibitor), because doing so can raise relugolix exposure and thereby heighten the likelihood of relugolix-related adverse reactions. When the two cannot be avoided, give relugolix first, keep the doses at least 6 hours apart, and increase how often you watch for adverse reactions. Relugolix may be paused for as long as 2 weeks to allow a brief course of certain P-gp inhibitors, and it should be restarted once the P-gp inhibitor is stopped. Should relugolix be held for more than 7 days, resume it using a loading dose of 360 mg on day one and then continue at 120 mg once daily. RifAMPin also acts as a combined P-gp and strong CYP3A inducer, and in that role its coadministration with relugolix may lower relugolix exposure, potentially diminishing relugolix's effects. In this case, raise the relugolix dose to 240 mg once daily1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of relugolix; induction of P-gp-mediated efflux transport of relugolix
How to manage this interaction
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. This combination is manageable when your team plans for it.
- Your care team may avoid this pairing when possible, or adjust your relugolix dose and individualize it for you.
- They may space the doses apart (relugolix first, then separate by at least 6 hours) and watch you more closely for side effects.
- If relugolix is paused and then restarted after more than a week, a loading dose may be used.
- Ask your pharmacist or doctor before starting, stopping, or changing either drug, and report any new side effects.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a study examining drug interactions, giving relugolix (a P-gp substrate) together with erythromycin (an inhibitor of P-gp and a moderate CYP3A inhibitor) raised relugolix AUC by 3.5-fold and Cmax by 2.9-fold 1.
b) Giving relugolix (a substrate of P-gp and CYP3A) together with rifAMPin (an inducer of P-gp and a strong CYP3A inducer) lowered relugolix AUC by 55% and Cmax by 23% 1.
Common questions
Can I take Relugolix and Rifampin together?
Rifampin can throw off your relugolix levels, either raising side-effect risk or making it less effective, so don't combine them without your care team adjusting the dose and monitoring you. Talk to your pharmacist or prescriber before changing anything. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Rifampin 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 Rifampin interaction managed?
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. This combination is manageable when your team plans for it. Your care team may avoid this pairing when possible, or adjust your relugolix dose and individualize it for you. They may space the doses apart (relugolix first, then separate by at least 6 hours) and watch you more closely for side effects. If relugolix is… 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 Rifampin 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: ORGOVYX oral tablets, relugolix oral tablets. Sumitomo Pharma America, Inc (per FDA), Marlborough, MA, 2025. DailyMed
Keep reading about Rifampin
Keep reading about Relugolix
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