Lenacapavir and Relugolix: 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
Lenacapavir
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.
Let's talk about taking lenacapavir (Sunlenca or Yeztugo) together with relugolix (Orgovyx). Lenacapavir can block a transporter called P-gp that normally helps move relugolix out of your body. When that transporter is slowed down, more relugolix can build up in your system. In a study with a similar blocker, relugolix levels rose about 3 times higher.
More relugolix means a higher chance of side effects like hot flashes, tiredness, or other reactions. The good news is your care team knows how to handle this. Please don't stop either medicine on your own. Just check in with your pharmacist or doctor so they can guide the timing and keep a closer eye on you.
Effect: Increased relugolix exposure via lenacapavir-mediated inhibition of intestinal P-gp efflux (relugolix is a P-gp substrate; neither drug's action here depends on prodrug activation).
Direction/magnitude: Increased relugolix AUC and Cmax, raising risk of relugolix-associated adverse effects. A study with erythromycin (P-gp inhibitor) showed ~3.5-fold AUC and ~2.9-fold Cmax increases.
Evidence: Probable. Severity: Major.
- Avoid concomitant use where 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 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 potential for relugolix-related adverse reactions. When coadministration cannot be avoided, give relugolix or relugolix/estradiol/norethindrone acetate first, allow at least a 6-hour gap between doses, and increase the frequency of monitoring for adverse reactions12. Relugolix therapy may be paused for up to 2 weeks to accommodate a brief course of certain P-gp inhibitors, resuming relugolix once the P-gp inhibitor has been stopped. Should relugolix be interrupted for more than 7 days, reinitiate it using a 360 mg loading dose on the first day, 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 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
The goal is to limit how much relugolix builds up. Your care team may:
- Avoid using the two together when there is another option.
- If both are needed, have you take relugolix first and separate the two doses by at least 6 hours.
- Watch you more closely for relugolix side effects.
- In some cases, briefly pause relugolix during a short course of the interacting drug, then restart it (with a loading dose if the pause is longer than 7 days).
What you should do: keep taking both exactly as prescribed and do not change anything yourself. 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 of relugolix by 3.5-fold and its Cmax by 2.9-fold 1.
Common questions
Can I take Lenacapavir and Relugolix together?
Lenacapavir can raise relugolix levels by blocking P-gp, increasing the risk of relugolix side effects, so your care team may separate the doses, monitor you closely, or adjust timing. Do not stop either medicine on your own; talk with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lenacapavir and Relugolix 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 Lenacapavir and Relugolix interaction managed?
The goal is to limit how much relugolix builds up. Your care team may: Avoid using the two together when there is another option. If both are needed, have you take relugolix first and separate the two doses by at least 6 hours. Watch you more closely for relugolix side effects. In some cases, briefly pause relugolix during a short course of the interacting drug, then restart it (with a loading dos… 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 Lenacapavir or Relugolix 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 Lenacapavir
Keep reading about Relugolix
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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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