Relugolix and Pibrentasvir: 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
Pibrentasvir
No brand names on record
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 relugolix (Orgovyx) along with pibrentasvir, a hepatitis C medicine. Here's what's going on: pibrentasvir can block a 'pump' in your gut called P-gp that normally limits how much relugolix gets into your body. When that pump is blocked, more relugolix builds up, which can raise your chance of side effects like hot flashes, fatigue, or other reactions.
The good news is that your care team can manage this. They may space the two medicines apart, watch you more closely, or adjust your plan. Please don't stop or change either medicine on your own, just talk with your pharmacist or doctor about the best timing.
Effect: Increased relugolix exposure. Relugolix is a P-gp substrate; pibrentasvir inhibits P-gp-mediated intestinal efflux, raising relugolix AUC and Cmax and the risk of relugolix-associated adverse effects.
- Direction: Increased relugolix effect (neither drug is a prodrug here).
- Magnitude: Study with erythromycin (a P-gp inhibitor) showed AUC 3.5-fold and Cmax 2.9-fold increases; used as reference.
- Evidence: Probable. Onset: unspecified.
- Management: Avoid concurrent use if possible. If unavoidable, give relugolix first, separate by at least 6 hours, and monitor adverse reactions more frequently. Relugolix may be interrupted up to 2 weeks for short P-gp inhibitor courses; if held >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 this 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, keep the doses at least 6 hours apart, 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, it should be reinitiated using a loading dose of 360 mg on day one, followed by 120 mg once daily thereafter. A drug interaction study demonstrated that giving relugolix (P-gp substrate) together with erythromycin (P-gp inhibitor) raised the AUC and Cmax of relugolix 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
Both medicines can be managed together with some planning by your care team. Based on the labeling, they may:
- Avoid combining them when possible.
- If both are needed, take relugolix first and separate the two doses by at least 6 hours.
- Watch you more closely for relugolix side effects.
- In some cases, pause relugolix during a short course of the other drug and restart it afterward (your team decides on any loading dose).
Keep taking both exactly as prescribed, and ask your pharmacist or doctor to confirm the best timing and monitoring plan for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a study of drug interactions, giving relugolix (a P-gp substrate) together with erythromycin (a P-gp inhibitor) raised relugolix's AUC by 3.5-fold and its Cmax by 2.9-fold 1.
Common questions
Can I take Relugolix and Pibrentasvir together?
Pibrentasvir can raise relugolix levels and side-effect risk by blocking its P-gp transporter; keep taking both as prescribed but ask your care team about separating doses by at least 6 hours (relugolix first) and closer monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Pibrentasvir 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 Pibrentasvir interaction managed?
Both medicines can be managed together with some planning by your care team. Based on the labeling, they may: Avoid combining them when possible. If both are needed, take relugolix first and separate the two doses by at least 6 hours. Watch you more closely for relugolix side effects. In some cases, pause relugolix during a short course of the other drug and restart it afterward (your team decides… 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 Pibrentasvir 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 Pibrentasvir
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