Drug Interaction Report

Milk Thistle and Relugolix: 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

Orgovyx Orgovyx®
+

Milk Thistle

No brand names on record
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Jul 2, 2026
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 9 documented Milk Thistle interactions, 5 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
At a glance + Effects may be stronger
The Bottom Line
Milk thistle can raise relugolix levels by slowing the P-gp pump that clears it, increasing side-effect risk, so it's best avoided; talk with your pharmacist or doctor before combining them or changing anything.

Here's what's going on. Relugolix (Orgovyx) is a medicine that leaves your body with the help of a little "pump" in your gut called P-gp. Milk thistle can slow that pump down. When the pump is slowed, more relugolix stays in your system than it should, which can raise your chance of side effects.

The good news is that this is very manageable. Please don't stop or change either one on your own. Just let your pharmacist or doctor know you're taking milk thistle (and any other supplements), and they can help you decide the safest plan, whether that's spacing them out or pausing the supplement.

Interaction: Milk thistle may inhibit P-gp-mediated efflux of relugolix (a P-gp substrate), increasing relugolix systemic exposure and the risk of adverse reactions.

  • Direction: Increased relugolix AUC/Cmax (relugolix is not a prodrug, so higher exposure means greater effect/toxicity risk).
  • Magnitude: Not quantified for milk thistle; a study with the P-gp inhibitor erythromycin raised relugolix AUC 3.5-fold and Cmax 2.9-fold.
  • Evidence: Probable. Onset: unspecified.
  • Management: Avoid concomitant use. If unavoidable, give relugolix first, separate by at least 6 hours, and monitor for adverse reactions more frequently. Interruption/restart per labeling if applicable.
Onset
unspecified
Evidence
probable
Severity
Major

What happens

Increased relugolix exposure

Interaction Deep Dive

Concurrent administration of relugolix (a P-gp substrate) with P-gp inhibitors should be avoided because it can raise relugolix exposure, potentially heightening the risk of adverse reactions linked to relugolix. 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. Relugolix therapy may be paused for as long as 2 weeks to accommodate 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, restart it using a loading dose of 360 mg on the first day, then continue at 120 mg once daily. In a drug interaction study, giving relugolix (P-gp substrate) together with erythromycin (P-gp inhibitor) raised relugolix AUC by 3.5-fold and Cmax by 2.9-fold1.

Why it happens (mechanism)

Inhibition of P-gp-mediated efflux transport of relugolix

How to manage this interaction

What your care team may do:

  • Generally advise avoiding milk thistle while on relugolix when possible.
  • If both are used, they may have you take relugolix first and separate the two by at least 6 hours.
  • Watch you more closely for relugolix side effects.
  • In some cases, relugolix may be paused during a short course of the interacting product and restarted afterward, with dosing individualized by your team.

What you should do: Keep taking relugolix as prescribed, and tell your pharmacist or doctor about milk thistle and any supplements before making any changes.

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 Milk Thistle and Relugolix together?

Milk thistle can raise relugolix levels by slowing the P-gp pump that clears it, increasing side-effect risk, so it's best avoided; talk with your pharmacist or doctor before combining them or changing anything. Always confirm with your pharmacist or prescriber before making any change.

How serious is the Milk Thistle and Relugolix 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 Milk Thistle and Relugolix interaction managed?

What your care team may do: Generally advise avoiding milk thistle while on relugolix when possible. If both are used, they may have you take relugolix first and separate the two by at least 6 hours. Watch you more closely for relugolix side effects. In some cases, relugolix may be paused during a short course of the interacting product and restarted afterward, with dosing individualized by your t… 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.

From our Q&A

Real reader questions about these medications, each personally answered by our pharmacist:

Questions for your pharmacist

  • Does my dose of Milk Thistle or Relugolix 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)

  1. Product Information: ORGOVYX oral tablets, relugolix oral tablets. Sumitomo Pharma America, Inc (per FDA), Marlborough, MA, 2025. DailyMed
  2. Product Information: MYFEMBREE(R) oral tablets, relugolix, estradiol, norethindrone acetate oral tablets. Myovant Sciences Inc (per FDA), Brisbane, CA, 2021. DailyMed
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Beyond drug–drug

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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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.