Relugolix and Diltiazem: 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
Diltiazem
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 diltiazem (a heart and blood pressure medicine) along with relugolix (Orgovyx). Here's what's going on: diltiazem slows down a 'pump' in your gut called P-gp that normally helps push relugolix back out. When that pump is slowed, more relugolix stays in your body. In studies with a similar drug, levels rose about 3 times higher.
More relugolix means a bigger chance of side effects like hot flashes, tiredness, or joint pain. The good news is your care team can handle this, often by spacing the doses apart, watching you more closely, or adjusting your plan. Please don't stop either medicine on your own, just talk with your pharmacist or doctor.
Effect: Diltiazem (P-gp inhibitor) increases exposure to relugolix (P-gp substrate) via inhibition of intestinal P-gp-mediated efflux. Relugolix is an active drug, not a prodrug, so inhibition raises its effect.
- Magnitude: A study with erythromycin (P-gp inhibitor) increased relugolix AUC ~3.5-fold and Cmax ~2.9-fold; expect a directionally similar rise with diltiazem.
- Evidence: Probable. Severity: Major. Onset unspecified.
- Management: Avoid concomitant use if possible. If unavoidable, give relugolix first and separate by at least 6 hours, and monitor more frequently for adverse reactions. Short P-gp inhibitor courses: relugolix may be interrupted 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 it 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 no less than 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 treatment with certain P-gp inhibitors. Relugolix should be resumed once the P-gp inhibitor has been stopped. When relugolix has been interrupted for more than 7 days, resume it with a 360 mg loading dose on the first day, followed by 120 mg once daily thereafter. In a drug interaction study, giving relugolix (P-gp substrate) together 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
Your care team has clear options to manage this safely. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your team may try to avoid using them together if a good alternative exists.
- If you do take both, they may have you take relugolix first and separate the two by at least 6 hours.
- They may monitor you more closely for relugolix side effects such as hot flashes, fatigue, or joint pain.
- For a short course of diltiazem, relugolix is sometimes paused and restarted afterward with a specific restart plan your prescriber will set.
Ask your pharmacist or doctor how to best space your doses and what side effects to watch for.
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 Relugolix and Diltiazem together?
Diltiazem can push relugolix levels significantly higher (roughly 3-fold in similar studies), raising the risk of side effects. Don't change anything on your own; ask your pharmacist or doctor about spacing doses and monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Diltiazem 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 Diltiazem interaction managed?
Your care team has clear options to manage this safely. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your team may try to avoid using them together if a good alternative exists. If you do take both, they may have you take relugolix first and separate the two by at least 6 hours. They may monitor you more closely for relugolix side effects such as hot… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Relugolix or Diltiazem 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 Diltiazem
Keep reading about Relugolix
These medications also interact with supplements
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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