Relugolix and Tepotinib: 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
Tepotinib
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.
These two medicines can affect each other. Tepotinib (Tepmetko) can block a 'pump' in your body called P-gp that normally helps move relugolix (Orgovyx) out. When that pump is slowed down, more relugolix stays in your blood. In studies with a similar pump-blocker, relugolix levels rose about 3-fold.
Higher relugolix levels can mean more of its usual side effects, like hot flashes, tiredness, or muscle and joint aches. The good news is your care team can manage this. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor so they can adjust timing or watch you more closely.
Mechanism: Tepotinib inhibits P-gp, reducing efflux of relugolix (a P-gp substrate), increasing relugolix systemic exposure. Neither drug is a prodrug here, so effect is enhanced relugolix activity/toxicity.
- Direction/magnitude: Increased relugolix AUC and Cmax. A study with erythromycin (P-gp inhibitor) showed ~3.5-fold AUC and ~2.9-fold Cmax increases.
- Evidence: Probable. Severity: Major. Onset: Unspecified.
- Management: Avoid coadministration if possible. If unavoidable, give relugolix first, separate dosing by >=6 hours, and monitor more frequently for adverse reactions. Relugolix may be interrupted up to 2 weeks for a short inhibitor course; if interrupted >7 days, restart with 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 doing so may raise relugolix exposure and thereby heighten the likelihood 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. 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, relugolix can be resumed. Should the relugolix interruption exceed 7 days, reinitiate with a 360 mg loading dose on the first day, followed by 120 mg once daily thereafter. In a drug interaction study, giving relugolix (P-gp substrate) together with erythromycin (P-gp inhibitor) raised relugolix AUC and Cmax 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
This is manageable with your care team's help. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your team will try to avoid using them together when possible, or tailor the plan for you.
- If both are needed, they may have you take relugolix first and separate the two doses by at least 6 hours, and watch you more closely for side effects.
- Sometimes relugolix is paused for a short course of the other drug and restarted afterward, with a specific restart dose your team will set.
Report any new or worsening side effects (hot flashes, fatigue, muscle or joint aches) to your pharmacist or doctor.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A drug interaction study found that 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 Tepotinib together?
Tepotinib can raise relugolix levels and side effects by blocking P-gp; your care team may separate the doses, monitor you more closely, or adjust the plan, so don't change either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Tepotinib 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 Tepotinib interaction managed?
This is manageable with your care team's help. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your team will try to avoid using them together when possible, or tailor the plan for you. If both are needed, they may have you take relugolix first and separate the two doses by at least 6 hours, and watch you more closely for side effects. Sometimes relugol… 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 Tepotinib 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 Tepotinib
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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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