Relugolix and Sotorasib: 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
Sotorasib
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.
Here's what's going on. Relugolix (Orgovyx) is moved out of your body with help from a little cellular pump called P-gp. Sotorasib (Lumakras) can slow that pump down. When the pump slows, more relugolix stays in your body, so its levels go up. In a similar study with another blocker, relugolix levels rose about 3.5 times.
Higher relugolix levels can mean more of its usual side effects, like hot flashes, tiredness, or diarrhea. The good news: this is very manageable. Your care team can space out the two medicines, watch you more closely, or adjust your plan. Please don't change anything on your own, just talk with your pharmacist or doctor.
Mechanism: Sotorasib inhibits P-gp-mediated efflux of relugolix (a P-gp substrate), increasing relugolix systemic exposure. Neither agent is being interpreted through prodrug activation; this is straightforward increased-substrate exposure.
Magnitude: By analogy to the erythromycin study, relugolix AUC increased ~3.5-fold and Cmax ~2.9-fold. Onset unspecified; evidence probable; severity major.
- Avoid concomitant use when possible.
- If unavoidable: give relugolix (or relugolix/estradiol/norethindrone) first, separate dosing by at least 6 hours, monitor for relugolix adverse reactions more frequently.
- Relugolix may be interrupted up to 2 weeks for a short P-gp inhibitor course; resume after discontinuation. If interrupted >7 days, restart with a 360 mg loading dose, then 120 mg daily.
What happens
Increased relugolix exposure
Interaction Deep Dive
Do not combine relugolix (a P-gp substrate) with P-gp inhibitors, because doing so can raise relugolix exposure and thereby heighten the likelihood of relugolix-related adverse reactions. When such 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 reactions 12. Relugolix therapy may be paused for as long as 2 weeks to accommodate a brief course of certain P-gp inhibitors, and relugolix should be resumed once the P-gp inhibitor has been stopped. Should relugolix be interrupted for more than 7 days, it should be restarted using a 360 mg loading dose on day one, followed by 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-fold 1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of relugolix
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. Here's how teams usually handle this combination:
- Where possible, they may avoid using the two together, or choose an alternative.
- If both are needed, they often take relugolix first and separate the doses by at least 6 hours.
- They may monitor you more closely for relugolix side effects (hot flashes, fatigue, diarrhea).
- Dosing may be adjusted and individualized by your team, including how relugolix is restarted after any pause.
Tell your pharmacist or prescriber that you take both, and report any new or worsening side effects.
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 of relugolix by 3.5-fold and its Cmax by 2.9-fold, respectively 1.
Common questions
Can I take Relugolix and Sotorasib together?
Sotorasib can raise relugolix levels and side effects by slowing a transporter that clears it, so your care team may avoid the combo, separate the doses by at least 6 hours, or monitor you more closely. Don't change anything on your own; check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Sotorasib 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 Sotorasib interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. Here's how teams usually handle this combination: Where possible, they may avoid using the two together, or choose an alternative. If both are needed, they often take relugolix first and separate the doses by at least 6 hours. They may monitor you more closely for relugolix side effects (hot flashes, fatigue, diarrhe… 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 Sotorasib 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 Sotorasib
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist