Relugolix and Mibefradil: 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
Relugolix
Mibefradil
No brand names on record
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 medicines can interact. Relugolix (Orgovyx) is cleared from your body partly by a 'pump' called P-glycoprotein, or P-gp, that moves the drug out of your cells. Mibefradil can block that pump. When the pump is blocked, more relugolix stays in your body, so its levels go up.
Higher relugolix levels can mean a higher chance of side effects. The good news is your care team can manage this. They may separate the timing of your doses, watch you more closely, or make other adjustments. Please don't stop or change either medicine on your own. Just talk with your pharmacist or doctor so they can plan the safest approach for you.
Effect: Increased relugolix exposure. Relugolix is a P-gp substrate; mibefradil inhibits P-gp-mediated intestinal efflux, reducing relugolix clearance and raising AUC/Cmax. Neither drug is a prodrug, so the direction is a straightforward increase in relugolix effect and adverse-reaction risk.
- Magnitude: By analogy, erythromycin (a P-gp inhibitor) raised relugolix AUC 3.5-fold and Cmax 2.9-fold.
- Evidence: Probable; severity major.
- Management: Avoid concurrent use if possible. If unavoidable, give relugolix first, separate dosing by at least 6 hours, and monitor for adverse reactions more frequently. Relugolix may be interrupted up to 2 weeks for short P-gp inhibitor courses; if held over 7 days, restart with a 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 it can raise relugolix exposure and thereby heighten the likelihood of adverse reactions linked to relugolix. When coadministration cannot be avoided, give relugolix or relugolix/estradiol/norethindrone acetate first, space the doses by a minimum of 6 hours, and increase the frequency of monitoring for adverse reactions 12. Relugolix therapy may be paused for up to 2 weeks to allow a brief course of treatment with certain P-gp inhibitors. Once the P-gp inhibitor has been stopped, relugolix can be resumed. Should relugolix be interrupted for more than 7 days, it should be restarted with a 360 mg loading dose on the first day, followed by 120 mg once daily thereafter. In a drug interaction study, coadministering relugolix (P-gp substrate) with erythromycin (P-gp inhibitor) raised relugolix AUC and Cmax by 3.5-fold and 2.9-fold, respectively 1.
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 these two together when possible.
- If both are needed, take relugolix first and separate the doses by at least 6 hours.
- Watch you more closely for relugolix side effects.
- For a short course of the interacting drug, they may pause relugolix and restart it afterward (with a loading dose if the pause is longer than 7 days).
What you should do: Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Let your pharmacist or doctor know you are on both so they can tailor timing, dosing, and monitoring for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a drug interaction study, 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 Mibefradil together?
Mibefradil can raise relugolix levels by blocking the P-gp pump, increasing the risk of side effects; avoid combining if possible, and if not, take relugolix first, separate doses by at least 6 hours, and let your care team monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Mibefradil 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 Mibefradil interaction managed?
What your care team may do: Try to avoid using these two together when possible. If both are needed, take relugolix first and separate the doses by at least 6 hours. Watch you more closely for relugolix side effects. For a short course of the interacting drug, they may pause relugolix and restart it afterward (with a loading dose if the pause is longer than 7 days). What you should do: Keep taking… 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 Mibefradil 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 Relugolix
Keep reading about Mibefradil
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