Clozapine and Relugolix: 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
Clozapine
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.
Both of these medicines can affect your heart's rhythm in a similar way. Clozapine (used for certain mental health conditions) and relugolix (Orgovyx, used for prostate cancer) can each stretch out a part of your heartbeat called the QT interval. When you take them together, that effect can add up and, in rare cases, lead to a dangerous irregular heartbeat.
The good news is your care team can manage this. They may check your heart with an EKG, keep an eye on blood minerals like potassium and magnesium, and decide the safest plan for you. Please don't stop either medicine on your own. Just talk with your pharmacist or doctor.
Effect: Additive QT-interval prolongation (PD interaction), increasing torsades de pointes risk.
Mechanism: Clozapine is an established QT-prolonging agent; relugolix-induced androgen deprivation may also prolong QT. Effects are additive. Neither is a prodrug and this is not a metabolic interaction.
Evidence: Theoretical. Severity: Major. Onset: Unspecified.
Management:
- Weigh benefit of androgen deprivation therapy vs risk, especially with congenital long QT, CHF, or recurrent electrolyte abnormalities.
- Avoid combination when possible.
- If required, correct/avoid hypokalemia and hypomagnesemia.
- 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 advantages of androgen deprivation therapy such as relugolix outweigh the possible hazards1. Where feasible, refrain from using relugolix alongside QT prolonging agents. Should combined administration be necessary, steer clear of agents that produce electrolyte disturbances (that is, hypokalemia or hypomagnesemia) 2, correct any electrolyte disturbances, and consider intermittent monitoring of ECGs and electrolytes 1.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
Both drugs can add to each other's effect on your heart rhythm, so your care team will watch this closely if you need both. Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
Your team may:
- Decide whether the benefit of relugolix outweighs the risk, especially if you have heart failure or a known heart-rhythm condition.
- Check periodic EKGs and blood electrolytes (potassium and magnesium), and correct any low levels.
- Choose an alternative when possible.
Tell your pharmacist or doctor if you feel fainting, dizziness, or a fluttering or racing heartbeat.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In an analysis of male patients undergoing androgen deprivation therapy (ADT) using individual case safety reports from the international pharmacovigilance database VigiBase, investigators identified 184 cases of acquired long-QT syndrome (aLQTS) and/or torsades de pointes (TdP; 11% of which were fatal), along with 99 cases of sudden death linked to ADT. The majority of aLQTS/TdP cases (62%) and sudden death cases (88%) related to ADT arose in the absence of exposure to other agents recognized to raise TdP risk; nevertheless, exposure to 1 drug and to 2 or more drugs carrying conditional, possible, or known TdP risk was documented in a portion of aLQTS/TdP events (23% or 43%) and sudden death events (18% and 22%). The agents regarded 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 demonstrated 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 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 receiving ADT chiefly 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 Clozapine and Relugolix together?
Clozapine and relugolix can each prolong the QT interval, and together the risk adds up, so your care team may monitor your EKG and electrolytes closely; keep taking both as prescribed and report any fainting or palpitations. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clozapine and Relugolix 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 Clozapine and Relugolix interaction managed?
Both drugs can add to each other's effect on your heart rhythm, so your care team will watch this closely if you need both. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your team may: Decide whether the benefit of relugolix outweighs the risk, especially if you have heart failure or a known heart-rhythm condition. Check periodic EKGs and blood electrolytes (po… 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 Clozapine or Relugolix 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 Clozapine
Keep reading about Relugolix
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