Relugolix and Velpatasvir: 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
Velpatasvir
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.
Let's talk about taking relugolix (Orgovyx) together with velpatasvir. Velpatasvir can block a 'pump' in your gut called P-gp that normally helps push relugolix back out. When that pump is slowed down, more relugolix gets into your body than usual. In a study using a similar blocker, relugolix levels went up about 3 times higher.
More relugolix in your system can mean more side effects, such as hot flashes, fatigue, or mood changes. The good news is this is very manageable. Don't stop or change anything on your own. Your care team can adjust timing, watch you more closely, or plan around it. Just make sure they know you take both.
Effect: Increased relugolix exposure via velpatasvir inhibition of intestinal P-glycoprotein (P-gp), reducing efflux of relugolix (a P-gp substrate). Relugolix is the active drug (not a prodrug), so higher exposure means greater pharmacologic and adverse effect.
Magnitude: With erythromycin (P-gp inhibitor), relugolix AUC increased ~3.5-fold and Cmax ~2.9-fold. Evidence: probable. Severity: major.
- Avoid concomitant use where possible.
- If unavoidable: give relugolix (or relugolix/estradiol/norethindrone) first, separate by at least 6 hours, 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 it can raise relugolix exposure and thereby heighten the likelihood of relugolix-related adverse reactions. When such combined use 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 allow a brief course of certain P-gp inhibitors, and relugolix can be resumed once the P-gp inhibitor is stopped. Should relugolix be interrupted for more than 7 days, it should be reinitiated with a 360 mg loading dose on day one, followed by 120 mg once daily thereafter. A drug interaction study showed 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
What your care team may do:
- Try to avoid using these two together when possible, or choose an alternative.
- 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.
- For a short course of the interacting drug, they may pause relugolix and restart it afterward (with a loading dose if it was held more than 7 days).
What you should do: Keep taking both exactly as prescribed unless told otherwise, and tell your pharmacist or prescriber you are on both so they can tailor timing and monitoring for you.
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 relugolix AUC by 3.5-fold and Cmax by 2.9-fold, respectively 1.
Common questions
Can I take Relugolix and Velpatasvir together?
Velpatasvir can raise relugolix levels and side effects by blocking a gut transporter; your care team can manage this by separating doses, monitoring closely, or adjusting therapy. Do not change your medications on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Velpatasvir 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 Velpatasvir interaction managed?
What your care team may do: Try to avoid using these two together when possible, or choose an alternative. 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. For a short course of the interacting drug, they may pause relugolix and restart it afterward (with a loading dose if it was held more than 7 days). What… 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 Velpatasvir 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 Velpatasvir
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