Tolvaptan and Relugolix: 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
Tolvaptan
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 gut in part by a natural "pump" called P-gp. Tolvaptan (Jynarque, Samsca) can block that pump, so more relugolix stays in your body. In a study using another P-gp blocker, relugolix levels rose about 3 to 4 times higher.
Higher relugolix levels can mean more side effects, like hot flashes, joint or muscle discomfort, or tiredness. The good news is your care team can manage this by spacing the doses out, watching you more closely, or adjusting your plan. Please don't stop or change either medicine on your own talk with your pharmacist or doctor first.
Effect: Increased relugolix exposure. Relugolix is a P-gp substrate; tolvaptan inhibits P-gp-mediated intestinal efflux, raising relugolix AUC/Cmax. Neither is a prodrug here, so the interaction increases active relugolix effect and adverse-reaction risk.
Magnitude: With erythromycin (P-gp inhibitor), relugolix AUC rose 3.5-fold and Cmax 2.9-fold. Evidence: probable. Severity: major.
- Avoid concomitant use where possible.
- If unavoidable, give relugolix (or relugolix/estradiol/norethindrone) first, separate by at least 6 hours, and monitor adverse reactions more frequently.
- Relugolix may be interrupted up to 2 weeks for a short P-gp inhibitor course; if held >7 days, restart with 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 doing so can raise relugolix exposure and thereby heighten the likelihood of relugolix-related adverse reactions. When the combination cannot be avoided, give relugolix or relugolix/estradiol/norethindrone acetate first, allow a minimum of 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 permit 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 reinitiated using a 360 mg loading dose on the first day, followed by 120 mg once daily thereafter. A drug interaction study demonstrated that giving relugolix (P-gp substrate) together with erythromycin (P-gp inhibitor) raised relugolix AUC by 3.5-fold and Cmax by 2.9-fold 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 how teams typically handle this:
- They may avoid using them together when another option exists.
- If both are needed, they may have you take relugolix first and separate the doses by at least 6 hours.
- They may watch you more closely for relugolix side effects.
- In some cases relugolix can be paused for a short course of the other drug, then restarted (sometimes with a loading dose) per your team.
Ask your pharmacist or prescriber about the best timing and whether any changes are needed 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 relugolix's AUC by 3.5-fold and its Cmax by 2.9-fold, respectively 1.
Common questions
Can I take Tolvaptan and Relugolix together?
Tolvaptan can raise relugolix levels several-fold and increase side effects, so use them together only under your care team's guidance, separating doses and monitoring closely. Do not start, stop, or change either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tolvaptan and Relugolix 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 Tolvaptan and Relugolix interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. Here is how teams typically handle this: They may avoid using them together when another option exists. If both are needed, they may have you take relugolix first and separate the doses by at least 6 hours. They may watch you more closely for relugolix side effects. In some cases relugolix can be paused for a short c… 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 Tolvaptan or Relugolix 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 Tolvaptan
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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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