Suvorexant 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
Suvorexant
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.
Here's what's going on. Relugolix (Orgovyx) is moved out of your body with the help of a 'pump' protein called P-gp. Suvorexant (Belsomra) can slow that pump down. When the pump is slowed, more relugolix stays in your body than intended, which can raise your chance of side effects from the relugolix.
The good news is this is very manageable. Please don't stop or change either medicine on your own. Just let your pharmacist or doctor know you take both. They may space the doses out, watch you a little more closely, or adjust your plan so both medicines stay safe and effective.
Mechanism: Suvorexant can inhibit P-glycoprotein (P-gp)-mediated efflux of relugolix, a P-gp substrate, increasing relugolix systemic exposure (increased AUC/Cmax) and raising the risk of relugolix-associated adverse reactions. Direction is increased exposure; neither drug is a prodrug here.
- Magnitude: Reference P-gp inhibitor (erythromycin) increased relugolix AUC 3.5-fold and Cmax 2.9-fold; suvorexant's specific magnitude is not quantified.
- Evidence: Probable. Severity: major. Onset: unspecified.
- Management: Avoid concomitant use if possible. If unavoidable, give relugolix first, separate dosing by at least 6 hours, and monitor for adverse reactions more frequently. For short P-gp inhibitor courses, relugolix may be interrupted up to 2 weeks; if interrupted >7 days, restart with a 360 mg loading dose then 120 mg daily.
What happens
Increased relugolix exposure
Interaction Deep Dive
The joint use of relugolix (a P-gp substrate) with P-gp inhibitors should be avoided, since this combination can raise relugolix exposure and thereby heighten the likelihood of relugolix-related adverse reactions. When coadministration cannot be prevented, give relugolix or relugolix/estradiol/norethindrone acetate first, keep the two doses at least 6 hours apart, and increase the frequency of monitoring for adverse reactions 12. 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 the interruption of relugolix exceed 7 days, reinitiate it using a loading dose of 360 mg 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, respectively 1.
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 possible, or choose an alternative.
- If both are needed, take relugolix first and separate the doses by at least 6 hours.
- Monitor you more closely for relugolix side effects.
- For a short course of the interacting drug, they may briefly pause relugolix and restart it afterward (with a loading dose if paused more than 7 days). Any dosing change should be individualized by your team.
What you should do: Keep taking both exactly as prescribed, and tell your pharmacist or prescriber you take both so they can set up the right spacing and monitoring.
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 Suvorexant and Relugolix together?
Suvorexant can raise relugolix levels and increase its side effects; don't change anything yourself, but tell your pharmacist or doctor so they can separate the doses, monitor you, or adjust your plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Suvorexant 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 Suvorexant and Relugolix interaction managed?
What your care team may do: Try to avoid using the two together when possible, or choose an alternative. If both are needed, take relugolix first and separate the doses by at least 6 hours. Monitor you more closely for relugolix side effects. For a short course of the interacting drug, they may briefly pause relugolix and restart it afterward (with a loading dose if paused more than 7 days). Any d… 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 Suvorexant 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 Suvorexant
Keep reading about Relugolix
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