Relugolix and Simeprevir: 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
Simeprevir
Relugolix
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.
You've been prescribed simeprevir (Olysio) and relugolix (Orgovyx) together. Here's what that means. Your body normally pumps some relugolix back out using a transporter called P-gp. Simeprevir slows that pump down, so more relugolix can stay in your body. Higher levels can mean a higher chance of side effects.
The good news is that this is very manageable. Your care team can space out when you take each medicine, watch you more closely, or adjust your plan. Please don't stop or change either drug on your own. Just talk with your pharmacist or doctor so they can set up the safest schedule for you.
Effect: Increased relugolix exposure. Simeprevir inhibits P-gp mediated intestinal efflux of relugolix (a P-gp substrate), raising its systemic exposure and adverse-reaction risk. Relugolix is not a prodrug, so inhibition increases active drug levels.
Magnitude: With erythromycin (a P-gp inhibitor), relugolix AUC rose 3.5-fold and Cmax 2.9-fold. Evidence: probable. Severity: major.
- Avoid concomitant use where possible.
- If unavoidable: give relugolix first, separate dosing by at least 6 hours, and monitor for adverse reactions more frequently.
- Relugolix may be interrupted up to 2 weeks for short P-gp inhibitor courses; 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 it can 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 treatment with 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 relugolix be interrupted for more than 7 days, reinitiate it 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 relugolix AUC by 3.5-fold and Cmax by 2.9-fold, respectively1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of relugolix
How to manage this interaction
What your care team may do:
- Try to avoid using the two together when a safer option exists.
- If both are needed, have you take relugolix first and separate the two doses by at least 6 hours.
- Monitor you more closely for relugolix side effects.
- In some cases pause relugolix during a short course of the interacting drug and resume it afterward, with the dosing individualized by your team.
What you should do: Keep taking both exactly as prescribed unless told otherwise. Ask your pharmacist or prescriber how to time your doses and what side effects to watch for.
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 Simeprevir together?
Simeprevir can raise relugolix levels and side-effect risk by blocking a transporter that clears it; your care team can manage this by spacing doses at least 6 hours apart, monitoring you, or adjusting your plan. Do not change anything on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Simeprevir 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 Simeprevir interaction managed?
What your care team may do: Try to avoid using the two together when a safer option exists. If both are needed, have you take relugolix first and separate the two doses by at least 6 hours. Monitor you more closely for relugolix side effects. In some cases pause relugolix during a short course of the interacting drug and resume it afterward, with the dosing individualized by your team. What you sh… 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 Simeprevir 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 Simeprevir
Keep reading about Relugolix
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