Relugolix and Zotepine: 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
Zotepine
No brand names on recordRelugolix
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. Zotepine is an antipsychotic, and relugolix (Orgovyx) is a hormone therapy. Both can lengthen a part of your heartbeat called the QT interval. When taken together, that effect can add up and, in rare cases, lead to an abnormal heart rhythm.
This is based mainly on how these drugs work rather than lots of reported cases, so try not to worry. Your care team can manage this well, often by checking your heart with an ECG and keeping your blood minerals (like potassium and magnesium) in a healthy range. Keep taking both as prescribed and talk with your doctor or pharmacist about any dizziness, fainting, or palpitations.
Effect: Additive QT interval prolongation with increased torsades risk.
Mechanism: Pharmacodynamic additive QT effect. Zotepine prolongs QT via cardiac repolarization delay; relugolix-induced androgen deprivation may independently prolong QT. Neither is a prodrug; this is a PD, not PK, interaction.
Evidence: Theoretical. Severity: Major. Onset: Unspecified.
Management:
- Avoid concomitant use where possible; weigh benefit of ADT against risk, especially with congenital long QT, CHF, or electrolyte disturbances.
- If combined, correct and avoid hypokalemia/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, clinicians should weigh whether the benefits of androgen deprivation therapy such as relugolix are greater than the possible risks 1. Where feasible, do not use relugolix concurrently with agents that prolong the QT interval. Should coadministration be necessary, refrain from using medications that produce electrolyte disturbances (that is, hypokalemia or hypomagnesemia) 2, correct any electrolyte abnormalities, and consider intermittent monitoring of ECGs and electrolytes 1.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
Both medicines can stretch the QT interval, so your care team will take steps to keep this safe.
- Keep taking both as prescribed unless your doctor tells you otherwise.
- Your team may avoid combining these when another option exists, and will weigh the benefits of your hormone therapy against the risks.
- They may check periodic ECGs and blood levels of potassium and magnesium, correcting any low levels.
- Tell your pharmacist or doctor about fainting, palpitations, or dizziness, and mention vomiting or diarrhea, which can lower minerals.
Your care team can individualize and monitor this closely.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A study assessing male patients on androgen deprivation therapy (ADT) using individual case safety reports from the international pharmacovigilance database VigiBase 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%) associated with ADT occurred without exposure to other agents known to raise TdP risk; nevertheless, exposure to 1 drug and to 2 or more drugs carrying conditional, possible, or known TdP risk was reported 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 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 receiving ADT chiefly to treat prostate cancer, with some being 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 Zotepine together?
Zotepine and relugolix can both prolong the QT interval, and combining them adds to that heart-rhythm risk. Keep taking both as prescribed and let your care team monitor your ECG and electrolytes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Zotepine 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 Zotepine interaction managed?
Both medicines can stretch the QT interval, so your care team will take steps to keep this safe. Keep taking both as prescribed unless your doctor tells you otherwise. Your team may avoid combining these when another option exists, and will weigh the benefits of your hormone therapy against the risks. They may check periodic ECGs and blood levels of potassium and magnesium, correcting any low leve… 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 Zotepine 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 Zotepine
Keep reading about Relugolix
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