Relugolix and Pirtobrutinib: 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
Pirtobrutinib
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 medications can interact. Pirtobrutinib (Jaypirca) can slow down a transporter in your body called P-gp that normally helps clear relugolix (Orgovyx) out. When that transporter is blocked, more relugolix can build up in your blood. In a similar study with another P-gp blocker, relugolix levels rose about 3 times higher.
Higher levels can mean a greater chance of side effects like hot flashes, tiredness, or other reactions tied to relugolix. The good news is your care team can manage this. Please don't stop or change either medicine on your own, just talk with your pharmacist or doctor so they can guide the timing and watch you more closely.
Effect: Increased relugolix exposure (relugolix is a P-gp substrate; pirtobrutinib inhibits intestinal P-gp-mediated efflux). Neither is a prodrug here, so the interaction increases relugolix activity and adverse-reaction risk.
Magnitude: A study with erythromycin (P-gp inhibitor) increased relugolix AUC 3.5-fold and Cmax 2.9-fold. Evidence: probable. Severity: major.
Management:
- Avoid concomitant use where possible.
- If unavoidable, give relugolix (or relugolix/estradiol/norethindrone) first and separate by at least 6 hours; monitor for adverse reactions more frequently.
- Relugolix may be interrupted up to 2 weeks for a short P-gp inhibitor course.
- If interrupted >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, because doing so 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, allow a gap of at least 6 hours between doses, and increase the frequency of monitoring for adverse reactions 12. For a brief course of certain P-gp inhibitors, relugolix therapy may be paused for as long as 2 weeks. Restart relugolix once the P-gp inhibitor has been stopped. Should relugolix be withheld for more than 7 days, resume it using a 360 mg loading dose on day one followed by a continued dose of 120 mg once daily. A drug interaction study showed that giving relugolix (P-gp substrate) together 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
Keep taking both exactly as prescribed unless your care team tells you otherwise. Here is what a team typically does with this combination:
- Separate the timing: take relugolix (or relugolix/estradiol/norethindrone) first, then wait at least 6 hours before the other medicine.
- Closer monitoring: your team may watch you more often for relugolix side effects.
- Possible interruption: for a short course of the interacting drug, relugolix may be paused for up to 2 weeks and restarted afterward (a loading dose may be used if the pause is longer than 7 days).
Ask your pharmacist or prescriber before making any change, and report new or worsening symptoms.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a study evaluating drug interactions, 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 Pirtobrutinib together?
Pirtobrutinib can raise relugolix levels by blocking P-gp, increasing side-effect risk, so avoid combining if possible; if used together, take relugolix first and separate doses by at least 6 hours under your care team's guidance. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Pirtobrutinib 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 Pirtobrutinib interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. Here is what a team typically does with this combination: Separate the timing: take relugolix (or relugolix/estradiol/norethindrone) first, then wait at least 6 hours before the other medicine. Closer monitoring: your team may watch you more often for relugolix side effects. Possible interruption: for a short course… 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 Pirtobrutinib 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 Pirtobrutinib
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