Relugolix and Histrelin: 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
Histrelin
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 relugolix (Orgovyx) and histrelin (Supprelin) work by lowering hormone levels, which is part of how they treat prostate cancer or other conditions. One side effect of this kind of hormone-lowering treatment is that it can slightly affect your heart's electrical rhythm, something called QT prolongation. When two drugs that can each do this are used together, the effect may add up.
This concern is mostly theoretical, so please don't panic. Keep taking both medicines as prescribed. Your care team can watch for this by checking your heart tracing (ECG) and your blood minerals when needed. If you ever feel fainting, dizziness, or a fluttering heartbeat, let them know.
Effect: Additive QT interval prolongation. Both agents lower androgens (GnRH antagonist relugolix; GnRH agonist histrelin), and androgen deprivation itself can prolong the QT interval, so combined use may be additive.
- Direction: Increased QT prolongation risk (PD interaction, not enzyme-based).
- Onset: Unspecified.
- Evidence: Theoretical.
- Severity: Major.
Management: Weigh benefit of ADT against risk in patients with congenital long QT, CHF, or electrolyte disturbances. Avoid concurrent use where possible. 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 or 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 in those receiving drugs recognized to prolong the QT interval, weigh whether the advantages of androgen deprivation therapy such as relugolix outweigh the possible hazards 1. Where feasible, do not use relugolix concurrently with QT prolonging agents. Should coadministration be necessary, refrain from using drugs that produce electrolyte abnormalities (that is, hypokalemia or hypomagnesemia) 2, correct any electrolyte abnormalities, and consider periodic monitoring of ECGs and electrolytes 1.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
Here is how a care team typically handles this combination:
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Your team will weigh the benefits of hormone therapy against your personal heart risk, especially if you have a history of long QT syndrome, heart failure, or low blood minerals.
- They may check periodic ECGs and electrolytes (potassium and magnesium) and correct any that are low.
- Tell your pharmacist or doctor about all other medicines you take, since some also affect QT.
Report any fainting, dizziness, or irregular heartbeat right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In an investigation of male patients undergoing androgen deprivation therapy (ADT) using individual case safety reports from VigiBase, the international pharmacovigilance database, researchers 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 without concurrent use of other agents recognized 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 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 about 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 primarily receiving ADT for prostate cancer, while some received it for prostatism and androgenic alopecia. Most patients were on ADT monotherapy (83%); 17% were on ADT combination therapy 3.
Common questions
Can I take Relugolix and Histrelin together?
Using relugolix and histrelin together may add to the risk of QT (heart rhythm) prolongation, though this is a theoretical concern. Keep taking both as prescribed and let your care team monitor your ECG and blood minerals. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Histrelin 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 Histrelin interaction managed?
Here is how a care team typically handles this combination: Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your team will weigh the benefits of hormone therapy against your personal heart risk, especially if you have a history of long QT syndrome, heart failure, or low blood minerals. They may check periodic ECGs and electrolytes (potassium and magnesium) and co… 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 Histrelin 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 Histrelin
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