Relugolix and Nirmatrelvir: 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
Nirmatrelvir
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.
Let's talk about taking relugolix (Orgovyx) together with nirmatrelvir, which is part of the COVID antiviral Paxlovid. Nirmatrelvir can slow down a 'pump' in your body called P-gp that normally helps clear relugolix out. When that pump is blocked, more relugolix can build up in your blood. In a similar study with another blocker, relugolix levels went up about 3 times higher.
Higher levels mean a greater chance of side effects like hot flashes, tiredness, or other reactions. The good news is that this is very manageable. Please don't change anything on your own, but do talk with your pharmacist or doctor so they can plan the safest way to handle both medicines.
Interaction: Nirmatrelvir inhibits P-gp-mediated efflux of relugolix (a P-gp substrate), increasing relugolix exposure. As a benchmark, erythromycin (P-gp inhibitor) raised relugolix AUC 3.5-fold and Cmax 2.9-fold.
- Direction: Increased relugolix exposure, greater risk of relugolix adverse effects.
- Severity/Evidence: Major; probable.
- Management: Avoid concomitant use if possible. If unavoidable, give relugolix first and separate dosing by at least 6 hours, with more frequent monitoring for adverse reactions.
- Relugolix may be interrupted up to 2 weeks for a short P-gp inhibitor course. If interrupted >7 days, restart with a 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 it can raise relugolix exposure and thereby heighten the potential for relugolix-related adverse reactions. When coadministration 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 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 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. Here is what they typically consider:
- Avoiding the overlap when possible, since nirmatrelvir courses are short (usually about 5 days).
- If both are needed, taking relugolix first and separating the doses by at least 6 hours, plus watching you more closely for side effects.
- Sometimes pausing relugolix briefly during the short antiviral course and restarting afterward (your team handles any loading dose).
What you should do: Keep taking both exactly as prescribed and tell your pharmacist or prescriber that you are on relugolix before starting the antiviral, so they can set up the right plan and timing.
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 the AUC and Cmax of relugolix by 3.5-fold and 2.9-fold, respectively 1.
Common questions
Can I take Relugolix and Nirmatrelvir together?
Nirmatrelvir can raise relugolix levels and its side effects; don't stop either drug on your own, but tell your pharmacist or doctor so they can separate the doses, monitor you, or briefly adjust relugolix. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Nirmatrelvir 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 Nirmatrelvir interaction managed?
Your care team can manage this safely. Here is what they typically consider: Avoiding the overlap when possible, since nirmatrelvir courses are short (usually about 5 days). If both are needed, taking relugolix first and separating the doses by at least 6 hours, plus watching you more closely for side effects. Sometimes pausing relugolix briefly during the short antiviral course and restarting aft… 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 Nirmatrelvir 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 Nirmatrelvir
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:
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