Relugolix and Nefazodone: 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
Nefazodone
No brand names on recordRelugolix
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've been prescribed relugolix (Orgovyx) along with nefazodone. Here's what's going on. Your body normally uses a kind of "pump" (called P-gp) to move relugolix out of your system. Nefazodone can slow that pump down, so more relugolix can build up in your body than expected. That higher level may raise your chance of side effects from the relugolix.
The good news is this is very manageable. Please don't stop or change either medicine on your own. Let your doctor or pharmacist know you take both so they can space out the doses, watch you more closely, or make another plan that keeps you safe.
Effect: Increased relugolix exposure. Nefazodone inhibits P-glycoprotein (P-gp), reducing efflux of relugolix (a P-gp substrate), raising its AUC and Cmax and the risk of relugolix-associated adverse reactions.
- Direction: Increased relugolix effect (neither drug is a prodrug here).
- Magnitude: Reference P-gp inhibitor erythromycin raised relugolix AUC ~3.5-fold and Cmax ~2.9-fold.
- Evidence/severity: Probable; rated major. Onset unspecified.
- Management: Avoid combination if possible. If unavoidable, give relugolix first, separate doses by >=6 hours, and monitor more frequently for adverse effects. Relugolix may be interrupted for short P-gp inhibitor courses; if held >7 days, restart with 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, 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 no less than 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, then resumed once the P-gp inhibitor has been stopped. Should relugolix be withheld for more than 7 days, reinitiate it using a 360 mg loading dose on day one and thereafter continue with 120 mg once daily. In a drug interaction study, giving relugolix (P-gp substrate) alongside 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
Your care team can manage this safely. Typical approaches include:
- Trying to avoid using the two together when another option exists.
- If both are needed, taking relugolix first and separating the doses by at least 6 hours.
- Monitoring you more closely for relugolix side effects.
- Sometimes briefly pausing relugolix during a short course of the other drug, then resuming (your prescriber will handle any restart dosing).
What you should do: keep taking both exactly as prescribed, and talk with your pharmacist or doctor before making any change so they can tailor the plan for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) During 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, respectively 1.
Common questions
Can I take Relugolix and Nefazodone together?
Nefazodone can raise relugolix levels and side-effect risk by blocking a transport pump; don't stop either drug on your own, but ask your pharmacist or doctor to space the doses and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Nefazodone 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 Nefazodone interaction managed?
Your care team can manage this safely. Typical approaches include: Trying to avoid using the two together when another option exists. If both are needed, taking relugolix first and separating the doses by at least 6 hours. Monitoring you more closely for relugolix side effects. Sometimes briefly pausing relugolix during a short course of the other drug, then resuming (your prescriber will handle a… 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 Nefazodone 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 Nefazodone
Keep reading about Relugolix
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