Relugolix and Ivacaftor: 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
Ivacaftor
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 little pump in your gut called P-gp. Ivacaftor (Kalydeco) can slow that pump down. When the pump slows, more relugolix stays in your body than usual, so the amount can build up.
More relugolix means a higher chance of side effects, like hot flashes, tiredness, or other reactions tied to the medicine. This is worth taking seriously, but it is very manageable. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor. They can adjust your plan, space out your doses, or watch you more closely so both drugs stay safe.
Mechanism: Ivacaftor inhibits P-glycoprotein (P-gp); relugolix is a P-gp substrate. Inhibition reduces intestinal efflux, increasing relugolix exposure. Neither drug is a prodrug, so the effect is a straightforward PK increase in relugolix.
Magnitude/direction: Increased relugolix AUC and Cmax (a strong P-gp inhibitor, erythromycin, raised AUC 3.5-fold and Cmax 2.9-fold). Onset unspecified; evidence probable; severity major.
Management:
- Avoid concurrent use when possible.
- If unavoidable, give relugolix first, separate by at least 6 hours, and monitor for 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 combination 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, allow a minimum of 6 hours between the two doses, 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, and relugolix can be resumed once the P-gp inhibitor has been stopped. Should relugolix treatment be interrupted for more than 7 days, it should be restarted using a loading dose of 360 mg on day one, followed by continuation at 120 mg once daily. A drug interaction study showed that coadministering relugolix (P-gp substrate) 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 good news is your care team can manage this. They will decide the safest approach, and you should keep taking both medicines exactly as prescribed until they advise you otherwise.
- Your team may avoid using the two together, or if both are needed, take relugolix first and separate the doses by at least 6 hours.
- They may watch you more closely for relugolix side effects during this time.
- In some cases relugolix can be paused briefly and restarted later (with a specific loading dose your team will handle).
What to do: Tell your pharmacist and prescriber you take both, and report any new or stronger side effects promptly.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) During a drug interaction study, the concurrent use of relugolix (a P-gp substrate) alongside 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 Ivacaftor together?
Ivacaftor can slow the pump that clears relugolix, raising relugolix levels and side-effect risk; don't stop either drug on your own, but let your pharmacist or doctor coordinate dosing, spacing, and monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Ivacaftor 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 Ivacaftor interaction managed?
The good news is your care team can manage this. They will decide the safest approach, and you should keep taking both medicines exactly as prescribed until they advise you otherwise. Your team may avoid using the two together, or if both are needed, take relugolix first and separate the doses by at least 6 hours. They may watch you more closely for relugolix side effects during this time. In some… 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 Ivacaftor 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 Ivacaftor
Keep reading about Relugolix
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