Relugolix and Zanubrutinib: 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
Zanubrutinib
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.
Let's talk about taking Brukinsa (zanubrutinib) and Orgovyx (relugolix) together. Zanubrutinib can block a pump in your gut called P-gp that normally helps push relugolix back out. When that pump is slowed down, more relugolix gets absorbed and builds up in your body. In a similar study with another P-gp blocker, relugolix levels went up about 3 times higher.
Higher levels can mean a greater chance of side effects from relugolix, like hot flashes, fatigue, or blood pressure changes. The good news is your care team can manage this by spacing the doses out and watching you a bit more closely. Please don't stop or change either medicine on your own, just check in with your pharmacist or doctor.
Effect: Zanubrutinib (P-gp inhibitor) increases exposure to relugolix (P-gp substrate) via inhibition of intestinal P-gp-mediated efflux. Neither drug is a prodrug; this is a straightforward increase in relugolix exposure.
Magnitude: No zanubrutinib-specific data; the erythromycin probe study showed relugolix AUC increased 3.5-fold and Cmax 2.9-fold. Evidence graded probable; severity major.
Management:
- Avoid concomitant use where possible.
- If unavoidable, give relugolix (or relugolix/estradiol/norethindrone) first, separate by at least 6 hours, and monitor more frequently for adverse reactions.
- Relugolix may be interrupted up to 2 weeks for a short P-gp inhibitor course; if held >7 days, restart with a 360 mg loading dose then 120 mg daily.
What happens
Increased relugolix exposure
Interaction Deep Dive
Do not combine relugolix (a P-gp substrate) with P-gp inhibitors, since doing so can raise relugolix exposure and thereby heighten the likelihood of relugolix-related adverse reactions. When such coadministration cannot be avoided, give relugolix or relugolix/estradiol/norethindrone acetate first, allow a gap of at least 6 hours between doses, and increase the frequency of monitoring for adverse reactions12. Relugolix therapy may be paused for as long as 2 weeks to accommodate 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 reintroduced using a loading dose of 360 mg on the first day, followed by 120 mg once daily thereafter. A drug interaction study found that giving relugolix (P-gp substrate) together with erythromycin (P-gp inhibitor) raised the AUC and Cmax of relugolix by 3.5-fold and 2.9-fold, respectively1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of relugolix
How to manage this interaction
Both drugs can be used, but your care team will take steps to keep relugolix from building up too much.
- Keep taking both as prescribed unless your prescriber tells you otherwise.
- Your team may separate the two medicines, taking relugolix first and spacing the doses by at least 6 hours.
- They may monitor you more closely for relugolix side effects.
- For a short course of the interacting drug, relugolix is sometimes paused; if it is held more than 7 days, your prescriber will restart it with a loading dose.
Ask your pharmacist or prescriber before starting, stopping, or changing either medicine, and report any new side effects.
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 relugolix AUC by 3.5-fold and Cmax by 2.9-fold 1.
Common questions
Can I take Relugolix and Zanubrutinib together?
Zanubrutinib can raise relugolix levels and side-effect risk by blocking P-gp; your care team can manage this by separating doses by at least 6 hours and monitoring you more closely, so don't change either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Zanubrutinib 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 Zanubrutinib interaction managed?
Both drugs can be used, but your care team will take steps to keep relugolix from building up too much. Keep taking both as prescribed unless your prescriber tells you otherwise. Your team may separate the two medicines, taking relugolix first and spacing the doses by at least 6 hours. They may monitor you more closely for relugolix side effects. For a short course of the interacting drug, relugol… 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 Zanubrutinib 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 Zanubrutinib
Keep reading about Relugolix
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