Relugolix and Doxepin: 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
Doxepin
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 doxepin (an antidepressant that's also used for sleep and itchy skin) and relugolix (Orgovyx, used to lower testosterone in prostate cancer). Both of these can affect the timing of your heartbeat, something doctors call the QT interval. When taken together, they can add up and slightly raise the chance of an irregular heart rhythm.
This concern is based on theory and how these drugs work, not on lots of reported cases. The good news is your care team can manage it easily, often with an occasional heart tracing (ECG) and blood tests to check your minerals like potassium. Keep taking both as prescribed and talk with your pharmacist or doctor about your heart history.
Effect: Additive QT interval prolongation with concurrent doxepin (a TCA with known QT effects) and relugolix (GnRH antagonist; androgen deprivation itself can prolong QT).
Direction/mechanism: Pharmacodynamic, additive delayed repolarization. Neither is a prodrug; interaction is PD, not PK.
Evidence: Theoretical. Severity: Major. Onset: Unspecified.
Management:
- Weigh benefit of ADT against risk in patients with congenital long QT, CHF, or electrolyte disturbances.
- Avoid combination when feasible.
- If required: avoid agents causing hypokalemia/hypomagnesemia, correct electrolyte abnormalities, 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 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 in those receiving drugs recognized for prolonging the QT interval, weigh whether the advantages of androgen deprivation therapy such as relugolix are greater than the possible risks 1. Where feasible, do not use relugolix alongside QT prolonging agents. Should combined use be necessary, steer clear of medications that produce electrolyte disturbances (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
Both medicines can lengthen the QT interval, so your care team may take a few simple precautions.
- Keep taking both as prescribed unless your doctor tells you otherwise.
- Your team may order occasional ECGs (heart tracings) and blood tests for electrolytes like potassium and magnesium.
- Correcting and avoiding low potassium or magnesium helps lower the risk.
- Where possible, your team may consider whether an alternative is appropriate.
Tell your pharmacist or prescriber if you have a personal or family history of long QT syndrome, heart failure, fainting, or palpitations, and mention any symptoms like dizziness or an irregular heartbeat.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A study assessed male patients on 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% 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%) associated with ADT arose without exposure to other agents known to raise TdP risk; nonetheless, exposure to 1 drug and to 2 or more drugs carrying conditional, possible, or known TdP risk was reported in some 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 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 for prostate cancer, with some treated for prostatism and androgenic alopecia. Most patients were on ADT monotherapy (83%), while 17% were on ADT combination therapy 3.
Common questions
Can I take Relugolix and Doxepin together?
Doxepin and relugolix can each stretch the QT interval, so together they may add up and slightly raise the risk of an irregular heartbeat. Keep taking both as prescribed, but ask your care team about ECG and electrolyte monitoring, especially if you have heart or rhythm problems. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Doxepin 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 Doxepin interaction managed?
Both medicines can lengthen the QT interval, so your care team may take a few simple precautions. Keep taking both as prescribed unless your doctor tells you otherwise. Your team may order occasional ECGs (heart tracings) and blood tests for electrolytes like potassium and magnesium. Correcting and avoiding low potassium or magnesium helps lower the risk. Where possible, your team may consider whe… 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 Doxepin 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 Doxepin
Keep reading about Relugolix
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