Relugolix and Leuprolide: 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
Relugolix
Leuprolide
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.
Both of these medicines lower testosterone to treat prostate cancer, and both can gently affect your heart's rhythm. They can each stretch out part of your heartbeat called the QT interval. When you take them together, that effect may add up, which in rare cases can lead to an irregular heartbeat.
The good news is that this is a theoretical concern, meaning it is based on how the drugs work rather than lots of real cases. Your care team can watch for it, especially if you have a known heart rhythm problem or low potassium or magnesium. Please don't stop either medicine on your own. Just talk with your doctor or pharmacist so they can keep an eye on things.
Effect: Additive QT interval prolongation. Both relugolix (GnRH antagonist) and leuprolide (GnRH agonist) can prolong the QT interval, largely via androgen deprivation, so concurrent use raises the theoretical risk of QTc prolongation and torsades.
Direction/mechanism: Pharmacodynamic (additive), not metabolic; neither is a prodrug relevant here.
Evidence: Theoretical. Severity: Major. Onset: Unspecified.
- Avoid concurrent use when possible.
- Weigh benefit/risk in congenital long QT, CHF, or recurrent electrolyte disturbance.
- If combined, avoid agents causing hypokalemia/hypomagnesemia, correct electrolytes, and consider periodic ECG and electrolyte monitoring.
What happens
Increased risk of QT interval prolongation
Interaction Deep Dive
When relugolix is given together with medications that prolong the QT interval, the effects on the QT interval are additive. The androgen deprivation produced by GnRH agonists and antagonists can itself lengthen the QT interval. In patients who have congenital long QT syndrome, congestive heart failure, or recurrent electrolyte disturbances, as well as those receiving drugs recognized to prolong the QT interval, weigh whether the benefits of androgen deprivation therapy such as relugolix are greater than the possible risks 1. Where feasible, do not use relugolix alongside QT prolonging agents. Should coadministration be necessary, refrain from using drugs that produce electrolyte disturbances (that is, hypokalemia or hypomagnesemia) 2, correct any electrolyte disturbances, and consider periodic monitoring of ECGs and electrolytes 1.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
Keep taking both medicines as prescribed unless your doctor tells you otherwise. Because both can affect heart rhythm, your care team weighs the benefits of this therapy against the risks, especially if you have a heart rhythm condition, heart failure, or trouble keeping your electrolytes balanced.
- Your team may check ECGs and blood electrolytes (like potassium and magnesium) from time to time.
- They will aim to correct any low potassium or magnesium and avoid other medicines that worsen those levels.
- Tell your pharmacist about all your medicines, and report symptoms like fainting, dizziness, or a pounding/irregular heartbeat right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A study examined male patients undergoing androgen deprivation therapy (ADT) using individual case safety reports from VigiBase, the international pharmacovigilance database, and found 184 cases of acquired long-QT syndrome (aLQTS) and/or torsades de pointes (TdP; 11% of cases fatal), along with 99 cases of sudden death linked to ADT. The majority of aLQTS/TdP cases (62%) and sudden death cases (88%) associated with ADT arose without concurrent use of other agents known to raise TdP risk; nevertheless, use of 1 drug and of 2 or more drugs carrying conditional, possible, or known TdP risk was reported in a portion of aLQTS/TdP (23% or 43%) and sudden death (18% and 22%) events. The agents classified as ADTs included abiraterone, gonadotropin-releasing hormone agonists and antagonists, nonsteroidal androgen receptor inhibitors indicated for prostate cancer, and 5-alpha-reductase inhibitors indicated for androgenic alopecia and prostatism. Among the 10 ADTs assessed, 7 showed a disproportional association (reporting odds ratio, 1.4 to 4.7) with aLQTS, TdP, or sudden death, namely leuprorelin, goserelin, triptorelin, degarelix, bicalutamide, finasteride, and dutasteride. The median patient age was approximately 76 years, and the median time to onset was 170 days (range, 7 to 4884 days) for aLQTS/TdP events and 92 days (range, 0.25 to 4984 days) for sudden death events. Patients were mainly receiving ADT for prostate cancer, while some were treated for prostatism and androgenic alopecia. Most patients were on ADT monotherapy (83%); 17% were receiving ADT combination therapy 3.
Common questions
Can I take Relugolix and Leuprolide together?
Relugolix and leuprolide can each prolong the QT interval, so together the effect may add up. This is a theoretical but serious concern that your care team can manage with electrolyte correction and periodic ECG monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Leuprolide 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 Leuprolide interaction managed?
Keep taking both medicines as prescribed unless your doctor tells you otherwise. Because both can affect heart rhythm, your care team weighs the benefits of this therapy against the risks, especially if you have a heart rhythm condition, heart failure, or trouble keeping your electrolytes balanced. Your team may check ECGs and blood electrolytes (like potassium and magnesium) from time to time. Th… 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 Leuprolide 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 (3)
- Product Information: ORGOVYX oral tablets, relugolix oral tablets. Sumitomo Pharma America, Inc (per FDA), Marlborough, MA, 2025. DailyMed
- Lyon AR, Lopez-Fernandez T, Couch LS, et al: 2022 ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J 2022; 43(41):4229-4361.
- Salem JE, Yang T, Moslehi JJ, et al: Androgenic effects on ventricular repolarization: a translational study from the international pharmacovigilance database to iPSC-cardiomyocytes. Circulation 2019; 140(13):1070-1080. PubMed
Keep reading about Relugolix
Keep reading about Leuprolide
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