Relugolix and Ketoconazole: 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
Ketoconazole
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 ketoconazole and relugolix (Orgovyx) together. Ketoconazole can block a 'pump' in your gut that normally helps push relugolix out of your body. When that pump is slowed down, more relugolix can build up, which can raise the chance of side effects.
On top of that, both medicines can affect your heart's rhythm (something called the QT interval), and together that effect can add up. This warning is mostly theoretical, so please don't worry or change anything on your own. Your care team knows how to handle this by adjusting timing, spacing doses out, or keeping a closer eye on you. Just let them know you take both.
Mechanism: Ketoconazole inhibits P-gp-mediated efflux of relugolix (a P-gp substrate), increasing relugolix exposure. Neither agent's activity depends on prodrug conversion here. Additive QT prolongation is also expected, as both drugs can prolong the QT interval.
- Direction: Increased relugolix exposure and additive QT risk.
- Evidence: Theoretical; onset unspecified.
- Management: Avoid coadministration if possible. If unavoidable, give relugolix first, separate by at least 6 hours, and monitor closely. Relugolix may be interrupted up to 2 weeks for short P-gp inhibitor courses; if held greater than 7 days, restart with a 360 mg loading dose then 120 mg daily. Correct electrolytes; consider periodic ECG and electrolyte monitoring, especially with LQTS, CHF, or electrolyte abnormalities.
What happens
Increased relugolix exposure and an increased risk of QT interval prolongation
Interaction Deep Dive
Do not combine relugolix (a P-gp substrate) with P-gp inhibitors, since doing so can raise relugolix exposure and thereby heighten the likelihood of adverse reactions. When such coadministration cannot be avoided, give the relugolix-containing product first, allow a gap of at least 6 hours between 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 a P-gp inhibitor, and relugolix can be resumed once the P-gp inhibitor is stopped. Should the relugolix interruption exceed 7 days, restart it using a 360 mg loading dose on day one, followed by 120 mg once daily thereafter1. Giving relugolix together with drugs that prolong the QT interval may produce additive effects on the QT interval. Weigh whether the benefits of androgen deprivation therapy such as relugolix outweigh the possible risks in individuals with congenital long QT syndrome, congestive heart failure, or recurrent electrolyte abnormalities, as well as in those receiving medications recognized to prolong the QT interval. Correct any electrolyte abnormalities and consider intermittent monitoring of ECGs and electrolytes1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of relugolix; additive QT interval prolongation
How to manage this interaction
Here is how a care team typically handles this combination:
- Avoiding the overlap when possible is preferred, since ketoconazole can raise relugolix levels.
- If both are needed, they may have you take relugolix first and space the doses by at least 6 hours, and watch you more closely for side effects.
- For a short ketoconazole course, your team may briefly pause relugolix and restart it afterward (with a loading dose if it has been held more than 7 days).
- They may check your electrolytes and ECG and correct any imbalances.
Keep taking both exactly as prescribed, and ask your pharmacist or doctor before making any changes or if you notice palpitations, dizziness, or fainting.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Giving relugolix (a P-gp substrate) together with erythromycin (a P-gp and CYP3A inhibitor) raised relugolix's AUC by 3.5-fold and its Cmax by 2.9-fold, respectively 1.
Common questions
Can I take Relugolix and Ketoconazole together?
Ketoconazole can increase relugolix levels and add to its heart-rhythm (QT) effect, so this pairing is usually avoided; if used together, your care team will space the doses, monitor you, and check ECG and electrolytes. Keep taking both as prescribed and confirm any changes with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Ketoconazole 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 Ketoconazole interaction managed?
Here is how a care team typically handles this combination: Avoiding the overlap when possible is preferred, since ketoconazole can raise relugolix levels. If both are needed, they may have you take relugolix first and space the doses by at least 6 hours, and watch you more closely for side effects. For a short ketoconazole course, your team may briefly pause relugolix and restart it afterward (wi… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Relugolix or Ketoconazole 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 Ketoconazole
Keep reading about Relugolix
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