Relugolix and Amitriptyline: 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
Amitriptyline
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. Amitriptyline (Elavil), an older antidepressant, and relugolix (Orgovyx), used to lower testosterone in prostate cancer, can each stretch out a part of the heartbeat called the QT interval. When you take them together, that effect can add up, which in rare cases could lead to an abnormal heart rhythm.
This concern is based on how the drugs work rather than lots of reported cases, so try not to worry. Please don't stop either medicine on your own. Let your pharmacist or doctor know you take both. They can watch your heart and your blood minerals to keep you safe.
Effect: Additive QT-interval prolongation (pharmacodynamic, not PK). Amitriptyline is a known QT-prolonging TCA; androgen deprivation from relugolix can itself prolong the QT interval. Neither is a prodrug relevant here; the risk is additive repolarization delay.
- Direction: Increased combined QT prolongation / torsades risk.
- Evidence: Theoretical; severity rated major.
- Higher-risk patients: Congenital long QT, CHF, electrolyte abnormalities.
- Management: Avoid concomitant use when possible. If required, correct and avoid hypokalemia/hypomagnesemia, and consider periodic ECG and electrolyte monitoring.
What happens
Increased risk of QT interval prolongation
Interaction Deep Dive
When relugolix is given alongside 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 risks1. 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 periodic monitoring of electrolytes and ECGs 1.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. Here is how a team usually handles this:
- They may decide whether an alternative to one drug is possible, especially if you have a heart condition or a history of low potassium or magnesium.
- If you stay on both, they may check ECGs and blood electrolytes periodically.
- They will aim to keep your potassium and magnesium in a healthy range.
Tell your pharmacist or doctor about any fainting, dizziness, or a pounding or irregular heartbeat, and mention all other medicines you take.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A study assessed male patients undergoing 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%) associated with ADT arose without exposure to other agents known to elevate TdP risk; nevertheless, exposure to 1 drug and to 2 or more drugs carrying conditional, possible, or known TdP risk was reported in some 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 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. 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 taking ADT chiefly to treat prostate cancer, with some receiving it 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 Amitriptyline together?
Taking amitriptyline and relugolix together can add up their effects on your heart's QT interval, so your care team may check ECGs and electrolytes or consider an alternative. Keep taking both as prescribed and report any fainting or irregular heartbeat. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Amitriptyline 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 Amitriptyline interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. Here is how a team usually handles this: They may decide whether an alternative to one drug is possible, especially if you have a heart condition or a history of low potassium or magnesium. If you stay on both, they may check ECGs and blood electrolytes periodically. They will aim to keep your potassium and magnesi… 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 Amitriptyline 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 Amitriptyline
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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