Relugolix and Paroxetine: 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
Paroxetine
Relugolix
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 paroxetine (Paxil) for mood and relugolix (Orgovyx) for prostate cancer. Paroxetine can act like a roadblock for one of the pumps (called P-gp) that helps move relugolix out of your body. When that pump is blocked, more relugolix can build up, which may raise the chance of side effects.
There's another point too: both medicines can slightly affect your heart's rhythm (the QT interval), and together that effect may add up. This concern is mostly theoretical, but it's worth taking seriously. The good news is your care team can manage this by adjusting timing, monitoring you more closely, and keeping an eye on your heart and electrolytes. Please don't change anything on your own, just talk with your doctor or pharmacist.
Mechanism: Paroxetine inhibits P-glycoprotein (P-gp), reducing efflux of the P-gp substrate relugolix and increasing relugolix exposure (AUC/Cmax). Both agents also carry QT-prolonging potential, giving additive PD risk. Neither is a prodrug here; effect is increased relugolix effect.
- Severity: major; evidence: theoretical; onset: unspecified.
- Management: Avoid combination if possible. If unavoidable, give relugolix first and separate dosing by at least 6 hours; monitor for adverse reactions.
- Relugolix may be interrupted up to 2 weeks for short P-gp inhibitor courses; if held >7 days, restart with 360 mg loading dose, then 120 mg daily.
- Correct electrolytes; consider periodic ECG and electrolyte monitoring, especially with cardiac risk factors.
What happens
Increased relugolix exposure and an increased risk of QT interval prolongation
Interaction Deep Dive
Concurrent administration of relugolix (a P-gp substrate) with P-gp inhibitors should be avoided, since it can raise relugolix exposure and thereby heighten the likelihood of adverse reactions. When coadministration cannot be avoided, give the relugolix-containing product first, allow a gap of at least 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 a P-gp inhibitor, with relugolix resumed once the P-gp inhibitor has been stopped. Should the interruption of relugolix last more than 7 days, reinitiate it using a 360 mg loading dose on day one, followed by a maintenance dose of 120 mg once daily1. When relugolix is given together with drugs that prolong the QT interval, the effects on the QT interval may be additive. In patients with congenital long QT syndrome, congestive heart failure, or recurrent electrolyte disturbances, as well as those receiving medications known to prolong the QT interval, weigh whether the benefits of androgen deprivation therapy such as relugolix outweigh the possible risks. Correct any electrolyte abnormalities and consider periodic ECG and electrolyte monitoring1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of relugolix; additive QT interval prolongation
How to manage this interaction
Both medicines are important, so don't stop either one on your own. Here's how a care team typically handles this:
- They may try to avoid combining them if a suitable alternative exists.
- If both are needed, they may have you take relugolix first and separate the doses by at least 6 hours, and watch you more closely for side effects.
- They may check your electrolytes and periodically monitor an ECG, especially if you have heart concerns.
- In some cases relugolix may be paused briefly during a short paroxetine course and restarted as directed by your team.
Ask your pharmacist or prescriber how to space your doses and whether any heart monitoring is planned.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Giving relugolix (a P-gp substrate) together with erythromycin (a P-gp and CYP3A inhibitor) raised the AUC of relugolix by 3.5-fold and its Cmax by 2.9-fold 1.
Common questions
Can I take Relugolix and Paroxetine together?
Paroxetine can raise relugolix levels and both may affect heart rhythm, so your care team may separate dosing, monitor you more closely, and check your heart and electrolytes. Keep taking both as prescribed and ask your pharmacist or doctor how to manage the timing. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Paroxetine 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 Paroxetine interaction managed?
Both medicines are important, so don't stop either one on your own. Here's how a care team typically handles this: They may try to avoid combining them if a suitable alternative exists. If both are needed, they may have you take relugolix first and separate the doses by at least 6 hours, and watch you more closely for side effects. They may check your electrolytes and periodically monitor an ECG,… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Relugolix or Paroxetine 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 Paroxetine
Keep reading about Relugolix
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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