Relugolix and Piperine: 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
Piperine
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.
You're taking relugolix (Orgovyx), and piperine is a natural compound found in black pepper and in some supplements. Piperine can block a natural "pump" in your gut called P-glycoprotein that normally limits how much relugolix your body absorbs. When that pump is slowed down, more relugolix can build up in your body.
More drug means a higher chance of side effects. The good news is this is very manageable. Please don't stop either one on your own. Just let your pharmacist or doctor know if you use pepper-based or piperine supplements, and they can guide timing, dosing, or whether the supplement is worth continuing.
Effect: Increased relugolix exposure. Relugolix is a P-gp substrate; piperine inhibits P-gp-mediated intestinal efflux, raising relugolix AUC and Cmax and increasing adverse-reaction risk.
Magnitude: Not quantified for piperine specifically. For reference, the P-gp inhibitor erythromycin raised relugolix AUC 3.5-fold and Cmax 2.9-fold.
Evidence: Probable. Onset: unspecified.
- Avoid concomitant use where possible.
- If unavoidable, give relugolix first, separate by at least 6 hours, and monitor for adverse reactions more frequently.
- If relugolix is interrupted >7 days, restart with a 360 mg loading dose, then 120 mg daily.
What happens
Increased relugolix exposure
Interaction Deep Dive
Do not use relugolix (a P-gp substrate) together with P-gp inhibitors, because this combination can raise relugolix exposure and thereby heighten the likelihood of relugolix-related adverse reactions. When coadministration cannot be avoided, give relugolix or relugolix/estradiol/norethindrone acetate first, keep the two doses at least 6 hours apart, and increase the frequency of monitoring for adverse reactions12. Relugolix therapy may be paused for as long as 2 weeks to allow 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, restart it using a loading dose of 360 mg on day one, then continue at 120 mg once daily. In a drug interaction study, giving relugolix (P-gp substrate) alongside erythromycin (P-gp inhibitor) raised relugolix AUC by 3.5-fold and Cmax by 2.9-fold1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of relugolix
How to manage this interaction
This is manageable with your care team's help. Keep taking relugolix exactly as prescribed and don't make changes on your own.
- Tell your pharmacist or doctor about any black pepper extract or piperine supplements you use.
- Where possible, the team may recommend avoiding the combination.
- If both are used, they may have you take relugolix first, separate dosing by at least 6 hours, and watch you more closely for side effects.
- Your team may adjust and individualize your plan, and if relugolix is paused for more than 7 days, they will restart it with a loading dose.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A drug interaction study found that 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 Piperine together?
Piperine can increase how much relugolix your body absorbs, which raises the risk of side effects. Talk with your pharmacist or doctor before combining them, and don't stop either on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Piperine 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 Piperine interaction managed?
This is manageable with your care team's help. Keep taking relugolix exactly as prescribed and don't make changes on your own. Tell your pharmacist or doctor about any black pepper extract or piperine supplements you use. Where possible, the team may recommend avoiding the combination. If both are used, they may have you take relugolix first, separate dosing by at least 6 hours, and watch you more… 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 Piperine 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 Piperine
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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