Relugolix and Lonafarnib: 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
Lonafarnib
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 lonafarnib (Zokinvy) together with relugolix (Orgovyx). Lonafarnib blocks a kind of pump in your body called P-gp that normally helps push relugolix back out of your system. When that pump is slowed down, more relugolix stays in your blood, so the effects and side effects of relugolix can be stronger than expected.
The good news is your care team can manage this. They may space the two medicines out, watch you more closely for side effects, or adjust your plan. Please don't stop or change anything on your own. Just check in with your pharmacist or doctor so they can set this up safely for you.
Effect: Increased relugolix exposure. Relugolix is a P-gp substrate; lonafarnib inhibits intestinal P-gp-mediated efflux, raising relugolix AUC and Cmax and the risk of relugolix-associated adverse reactions.
- Direction: Increased relugolix effect (higher exposure).
- Magnitude: A study with erythromycin (P-gp inhibitor) raised relugolix AUC 3.5-fold and Cmax 2.9-fold; lonafarnib effect may differ but is expected qualitatively similar.
- Evidence: Probable. Severity: Major.
Management: Avoid coadministration if possible. If unavoidable, give relugolix first, separate by at least 6 hours, and monitor more frequently. Short courses of a P-gp inhibitor may allow interrupting relugolix up to 2 weeks; 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 relugolix-related adverse reactions. When coadministration cannot be avoided, give relugolix or relugolix/estradiol/norethindrone acetate first, allow a gap of at least 6 hours between doses, and increase the frequency of monitoring for adverse reactions12. For a brief course of 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. If the relugolix interruption exceeds 7 days, reinitiate relugolix using a loading dose of 360 mg on day one, followed by 120 mg once daily thereafter. A drug interaction study found that giving relugolix (P-gp substrate) together with erythromycin (P-gp inhibitor) raised relugolix AUC by 3.5-fold and Cmax by 2.9-fold1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of relugolix
How to manage this interaction
Both medicines can be used together safely when your care team plans for it. Here is what they typically do:
- Prefer avoiding the combination when another option exists.
- If both are needed: take relugolix first and separate the two doses by at least 6 hours, with more frequent checks for side effects.
- For a short course of the interacting drug, your prescriber may briefly pause relugolix and resume it afterward (with a loading dose if it was held more than 7 days).
Keep taking both exactly as prescribed, and ask your pharmacist or doctor how to time your doses. Your dose and monitoring can be adjusted and individualized by your care team.
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 Relugolix and Lonafarnib together?
Lonafarnib can raise relugolix levels and side effects by blocking its P-gp transport. Don't change anything yourself; ask your care team about separating doses, closer monitoring, or a brief pause. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Lonafarnib 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 Lonafarnib interaction managed?
Both medicines can be used together safely when your care team plans for it. Here is what they typically do: Prefer avoiding the combination when another option exists. If both are needed: take relugolix first and separate the two doses by at least 6 hours, with more frequent checks for side effects. For a short course of the interacting drug, your prescriber may briefly pause relugolix and resume… 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 Lonafarnib 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 Lonafarnib
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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