Relugolix and Promethazine: 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
Promethazine
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 promethazine (often used for nausea or allergies) and relugolix (Orgovyx, used for prostate cancer). Both of these medicines can, on their own, slightly affect the timing of your heartbeat, a change on the EKG called QT prolongation. When taken together, that effect can add up, which in rare cases could lead to an irregular heartbeat.
The good news is this concern is based mostly on theory, not a common real-world problem. Your care team can manage it easily by keeping an eye on your heart rhythm and your blood minerals (like potassium and magnesium). Please don't stop either drug on your own. Just talk with your pharmacist or doctor so they can decide what's safest for you.
Effect: Additive QT interval prolongation when promethazine (a phenothiazine with known QT effects) is combined with relugolix. Androgen deprivation from GnRH antagonists like relugolix can itself prolong the QT interval; the combination is additive (PD interaction, not CYP-mediated).
- Direction: Increased risk of QT prolongation / torsades de pointes.
- Evidence: Theoretical; severity: major; onset unspecified.
- Management: Avoid concomitant use where possible. If required, correct and avoid hypokalemia/hypomagnesemia, and consider periodic ECG and electrolyte monitoring. Weigh benefit/risk in congenital long QT, CHF, or frequent electrolyte disturbances.
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 risks1. Where feasible, do not use relugolix alongside QT prolonging agents. Should coadministration be necessary, steer clear of 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
Both drugs can nudge your heart's rhythm in the same direction, so your care team's goal is to keep that in check.
- Keep taking both as prescribed unless your doctor tells you otherwise.
- Your team may check periodic EKGs and monitor your electrolytes (potassium and magnesium), correcting any that are low.
- Where possible, your prescriber may consider whether an alternative to promethazine is a better fit.
- Tell your care team if you feel fainting, dizziness, palpitations, or an irregular heartbeat, and mention any vomiting or diarrhea, since these can lower electrolytes.
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 VigiBase, the international pharmacovigilance database, identified 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%) related to ADT arose without concurrent use of other agents known to raise TdP risk; nevertheless, use of 1 drug and 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 classified as ADTs comprised 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 on ADT chiefly for prostate cancer, with some treated for prostatism and androgenic alopecia. Most patients received ADT as monotherapy (83%); 17% were on ADT combination therapy 3.
Common questions
Can I take Relugolix and Promethazine together?
Promethazine and relugolix can each prolong the QT interval, so together the effect adds up; keep taking both as prescribed, and let your care team monitor your heart rhythm and electrolytes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Promethazine 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 Promethazine interaction managed?
Both drugs can nudge your heart's rhythm in the same direction, so your care team's goal is to keep that in check. Keep taking both as prescribed unless your doctor tells you otherwise. Your team may check periodic EKGs and monitor your electrolytes (potassium and magnesium), correcting any that are low. Where possible, your prescriber may consider whether an alternative to promethazine is a bette… 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 Promethazine 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 Promethazine
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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