Cobicistat 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
Cobicistat
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 relugolix (Orgovyx) along with cobicistat (Tybost). Here's what's going on. Cobicistat blocks a 'pump' in your gut called P-gp that normally limits how much relugolix gets absorbed. With that pump slowed down, more relugolix ends up in your body. In studies with a similar drug, levels rose about 3 times higher.
More relugolix means a higher chance of side effects, like hot flashes, tiredness, or other reactions. This is very manageable. Your care team may adjust timing, watch you more closely, or make other changes. Please don't stop either medicine on your own. Just talk with your pharmacist or doctor.
Effect: Cobicistat (P-gp inhibitor) increases relugolix (P-gp substrate) exposure via inhibition of intestinal P-gp-mediated efflux, raising the risk of relugolix-associated adverse reactions.
Magnitude: Not studied directly with cobicistat; a comparable P-gp inhibitor (erythromycin) increased relugolix AUC 3.5-fold and Cmax 2.9-fold. Evidence: probable. Onset: unspecified.
Management:
- Avoid coadministration where possible.
- If unavoidable, give relugolix first and separate dosing by at least 6 hours.
- Monitor more frequently for adverse reactions.
- Relugolix may be interrupted up to 2 weeks for short P-gp inhibitor courses; if interrupted more than 7 days, restart with a 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, space the doses by a minimum of 6 hours, 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. Resume relugolix once the P-gp inhibitor has been stopped. Should relugolix be interrupted for more than 7 days, reinitiate it with a 360 mg loading dose on day one, then continue at 120 mg once daily. In a drug interaction study, coadministering relugolix (P-gp substrate) with erythromycin (P-gp inhibitor) produced 3.5-fold and 2.9-fold increases in the AUC and Cmax of relugolix, respectively1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of relugolix
How to manage this interaction
The goal here is to keep relugolix from building up too much. Your care team has clear options:
- Avoiding the combination when possible is preferred.
- If both are needed, take relugolix first and separate the two doses by at least 6 hours.
- Your team may monitor you more closely for side effects.
- For short courses of cobicistat, relugolix may be paused for up to 2 weeks and restarted afterward (with a loading dose if paused more than 7 days).
What you should do: keep taking both exactly as prescribed, and ask your pharmacist or prescriber how they want you to space or adjust these medicines. Report any new or worsening side effects.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) During a drug interaction study, 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 Cobicistat and Relugolix together?
Cobicistat can raise relugolix levels and side-effect risk by blocking P-gp; your care team can manage this by avoiding the combo, spacing doses at least 6 hours apart, or monitoring you closely. Don't change either medicine on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cobicistat 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 Cobicistat and Relugolix interaction managed?
The goal here is to keep relugolix from building up too much. Your care team has clear options: Avoiding the combination when possible is preferred. If both are needed, take relugolix first and separate the two doses by at least 6 hours. Your team may monitor you more closely for side effects. For short courses of cobicistat, relugolix may be paused for up to 2 weeks and restarted afterward (with… 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 Cobicistat 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 Cobicistat
Keep reading about Relugolix
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major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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