Relugolix and Sotagliflozin: 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
Sotagliflozin
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.
What's going on: Relugolix (Orgovyx) is cleared from your body partly by a natural "pump" called P-gp that pushes the drug back out of your gut. Sotagliflozin (Inpefa) can slow that pump down. When the pump is slowed, more relugolix stays in your body, so the levels can climb higher than expected.
Higher relugolix levels can mean a greater chance of side effects like hot flashes, fatigue, or other reactions. The good news is this is very manageable. Don't stop or change either medicine on your own. Your pharmacist or doctor can adjust timing, watch you more closely, or pick another option if needed.
Mechanism: Relugolix is a P-gp substrate; sotagliflozin inhibits intestinal P-gp-mediated efflux, reducing relugolix clearance and increasing its systemic exposure (increased AUC/Cmax). Neither drug is a prodrug, so the effect is a direct increase in relugolix effect and adverse-reaction risk.
- Direction: Increased relugolix exposure.
- Magnitude reference: Erythromycin (P-gp inhibitor) raised relugolix AUC 3.5-fold and Cmax 2.9-fold.
- Evidence: Probable. Severity major. Onset unspecified.
- Management: Avoid if possible. If unavoidable, give relugolix (or relugolix/estradiol/norethindrone) first, separate by at least 6 hours, and monitor for adverse reactions more frequently.
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 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. 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 interrupted for more than 7 days, reinitiate it with a 360 mg loading dose on day one, followed by 120 mg once daily thereafter. In a drug interaction study, giving relugolix (P-gp substrate) together with erythromycin (P-gp inhibitor) raised relugolix AUC and Cmax 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
The care team's usual approach: Because sotagliflozin can raise relugolix levels, prescribers often avoid using them together when there's another option. When both are truly needed, the team can manage it safely.
- Keep taking both exactly as prescribed unless your provider tells you otherwise.
- Your team may have you take relugolix first and separate the two doses by at least 6 hours.
- Expect closer monitoring for relugolix side effects.
- For short-term P-gp inhibitor courses, relugolix may be paused and restarted by your provider (with a loading dose if paused more than 7 days).
Ask your pharmacist or doctor before combining these two.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a study examining drug interactions, 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 1.
Common questions
Can I take Relugolix and Sotagliflozin together?
Sotagliflozin can push relugolix levels higher and increase side effects, so this combination is best avoided; if both are needed, your care team can separate the doses by at least 6 hours and monitor you more closely. Talk to your pharmacist or doctor before taking them together. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Sotagliflozin 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 Sotagliflozin interaction managed?
The care team's usual approach: Because sotagliflozin can raise relugolix levels, prescribers often avoid using them together when there's another option. When both are truly needed, the team can manage it safely. Keep taking both exactly as prescribed unless your provider tells you otherwise. Your team may have you take relugolix first and separate the two doses by at least 6 hours. Expect closer… 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 Sotagliflozin 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 Sotagliflozin
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist