Relugolix and St John's Wort: 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
St John's Wort
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.
St. John's Wort can weaken your relugolix (Orgovyx). St. John's Wort is a strong herbal 'inducer,' meaning it can speed up how your body pushes relugolix out. When that happens, there may not be enough relugolix in your system to do its job of lowering your hormone levels, so the treatment could work less well.
The good news is that this is manageable. Please don't start, stop, or change either one on your own. Let your doctor or pharmacist know you take (or are thinking about taking) St. John's Wort. They can decide whether to adjust your relugolix dose or choose a safer option so your treatment keeps working the way it should.
Interaction: St. John's Wort induces intestinal P-gp (and CYP3A), reducing relugolix exposure and potentially compromising efficacy. Relugolix is a P-gp substrate; it is not a prodrug, so induction lowers active drug levels.
- Direction: Predominantly reduced relugolix AUC/Cmax with a chronic inducer like St. John's Wort, risking loss of hormonal suppression.
- Evidence/severity: Probable mechanism; rated major.
- Management: Avoid combined P-gp/strong CYP3A inducers with relugolix where possible. Per labeling, if coadministration with such inducers is required, increase relugolix to 240 mg once daily and monitor clinical response. Individualize with the care team.
What happens
Altered relugolix exposure, an increased risk of relugolix-related adverse reactions and reduced efficacy of relugolix
Interaction Deep Dive
The combination of relugolix with rifAMPin (an oral P-gp inhibitor) should not be used, because relugolix exposure may rise and thereby heighten the likelihood of adverse reactions linked to relugolix. When coadministration cannot be avoided, give relugolix first, keep the two doses at least 6 hours apart, and check for adverse reactions with greater frequency. For a brief course of certain P-gp inhibitors, relugolix therapy may be paused for as long as 2 weeks. Once the P-gp inhibitor has been stopped, restart relugolix. Should relugolix be withheld for more than 7 days, resume it using a 360 mg loading dose on the first day, followed by 120 mg once daily thereafter. Because rifAMPin is also a combined P-gp and strong CYP3A inducer, coadministering it with relugolix may instead lower relugolix exposure, potentially diminishing the effects of relugolix. In that case, raise the relugolix dose to 240 mg once daily1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of relugolix; induction of P-gp-mediated efflux transport of relugolix
How to manage this interaction
Keep taking your relugolix as prescribed and tell your care team about any St. John's Wort use, including supplements you buy over the counter.
- Because St. John's Wort can lower relugolix levels, your team may prefer you avoid this combination.
- If the two must be used together, the relugolix dose may need to be adjusted and individualized (the label supports increasing to 240 mg once daily with a strong inducer), and your team may monitor your response more closely.
- Do not start or stop either product on your own. Ask your pharmacist before adding any new herbal or OTC product.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A drug interaction study found that giving relugolix (a P-gp substrate) together with erythromycin (a P-gp and moderate CYP3A inhibitor) raised the AUC and Cmax of relugolix by 3.5-fold and 2.9-fold, respectively 1.
b) Administering relugolix (a P-gp and CYP3A substrate) alongside rifAMPin (a P-gp and strong CYP3A inducer) reduced the AUC and Cmax of relugolix by 55% and 23%, respectively 1.
Common questions
Can I take Relugolix and St John's Wort together?
St. John's Wort can speed up clearance of relugolix and make it less effective, so avoid the combination if you can; if you take both, talk to your doctor or pharmacist about a possible dose increase and closer monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and St John's Wort 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 St John's Wort interaction managed?
Keep taking your relugolix as prescribed and tell your care team about any St. John's Wort use, including supplements you buy over the counter. Because St. John's Wort can lower relugolix levels, your team may prefer you avoid this combination. If the two must be used together, the relugolix dose may need to be adjusted and individualized (the label supports increasing to 240 mg once daily with 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 St John's Wort 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 (1)
- Product Information: ORGOVYX oral tablets, relugolix oral tablets. Sumitomo Pharma America, Inc (per FDA), Marlborough, MA, 2025. DailyMed
Keep reading about St John's Wort
Keep reading about Relugolix
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