Relugolix and Fluoxetine: 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
Fluoxetine
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 two medicines that can each affect your heart's rhythm. Fluoxetine (a common antidepressant) and relugolix (Orgovyx, used for prostate cancer) can both stretch out part of your heartbeat called the QT interval. When taken together, that effect can add up, which in rare cases can lead to an irregular heartbeat.
I want to be clear that this is a possible risk based on how these drugs work, not something that happens to everyone. Your care team can manage it by keeping an eye on your heart tracing (ECG) and blood minerals like potassium and magnesium. Please don't stop either medicine on your own, just talk with your doctor or pharmacist.
Effect: Additive QT interval prolongation with concomitant fluoxetine and relugolix.
- Mechanism: Pharmacodynamic additive QT effect. Fluoxetine has known QT-prolonging potential; androgen deprivation from GnRH antagonists like relugolix may also prolong QT. Neither is a prodrug here; this is a PD interaction, not PK.
- Evidence/onset: Theoretical; onset unspecified. Severity rated major.
- Management: Avoid combination when possible. If required, correct and avoid hypokalemia/hypomagnesemia, and consider periodic ECG and electrolyte monitoring. Weigh risk in congenital long QT, CHF, or frequent electrolyte disturbance.
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. GnRH agonists and antagonists can lengthen the QT interval through the androgen deprivation they produce. 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 advantages of androgen deprivation therapy such as relugolix are greater than the possible hazards 1. Where feasible, do not combine relugolix with agents that prolong the QT interval. Should coadministration be necessary, refrain from using drugs that produce electrolyte disturbances (that is, hypokalemia or hypomagnesemia) 2, correct any electrolyte abnormalities, and consider periodically monitoring ECGs and electrolytes 1.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
Both drugs can affect heart rhythm, so your care team has a clear way to keep you safe.
- Keep taking both exactly as prescribed unless your doctor tells you otherwise.
- Your team may check periodic ECGs and blood electrolytes (potassium and magnesium), and correct any low levels.
- Tell your prescriber if you have a history of long QT syndrome, heart failure, or frequent electrolyte problems.
- Report symptoms like fainting, palpitations, or dizziness promptly.
- Ask your pharmacist before adding new medicines, since some also affect QT.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A study looked at male patients treated with androgen deprivation therapy (ADT) using individual case safety reports from VigiBase, the international pharmacovigilance database, and identified 184 cases of acquired long-QT syndrome (aLQTS) and/or torsades de pointes (TdP; 11% fatal cases), along with 99 cases of sudden death linked to ADT. The majority of aLQTS/TdP cases (62%) and sudden death cases (88%) tied to ADT arose without concurrent use of other drugs known to raise TdP risk; nevertheless, use of 1 drug and 2 or more drugs carrying conditional, possible, or known TdP risk was documented 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 patients had a median age of roughly 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, with some being treated for prostatism and androgenic alopecia. The majority were on ADT monotherapy (83%); 17% were receiving ADT combination therapy 3.
Common questions
Can I take Relugolix and Fluoxetine together?
Fluoxetine and relugolix can each prolong the QT interval, and together the effect may add up. Your care team can manage this with ECG and electrolyte monitoring, so keep taking both as prescribed and report fainting or palpitations. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Fluoxetine 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 Fluoxetine interaction managed?
Both drugs can affect heart rhythm, so your care team has a clear way to keep you safe. Keep taking both exactly as prescribed unless your doctor tells you otherwise. Your team may check periodic ECGs and blood electrolytes (potassium and magnesium), and correct any low levels. Tell your prescriber if you have a history of long QT syndrome, heart failure, or frequent electrolyte problems. Report s… 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.
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 Fluoxetine 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 Fluoxetine
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:
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