Relugolix and Protriptyline: 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
Protriptyline
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.
Both of these medicines can affect your heart's rhythm. Protriptyline is a tricyclic antidepressant, and relugolix (Orgovyx) is used to treat prostate cancer by lowering testosterone. Each one can slightly stretch out a part of your heartbeat called the QT interval. When you take them together, that effect can add up, which in rare cases can lead to an irregular heartbeat.
This concern is based on how the drugs work rather than lots of real-world reports, so please don't be alarmed. Keep taking both exactly as prescribed. Your care team can manage this by checking your heart tracing (ECG) and blood minerals now and then. Ask your pharmacist or doctor if you have questions.
Effect: Additive QT interval prolongation with concurrent protriptyline (a TCA with known QT liability) and relugolix (androgen deprivation therapy can prolong QT).
- Mechanism: Pharmacodynamic additive QTc prolongation (not a metabolic/prodrug interaction).
- Direction: Increased torsades risk.
- Evidence: Theoretical; severity rated major.
- Onset: Unspecified.
- Management: Weigh benefit vs risk, especially in congenital long QT, CHF, or electrolyte disturbances. Avoid combination when possible. If required, correct and avoid hypokalemia/hypomagnesemia and perform 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, weigh whether the advantages of androgen deprivation therapy such as relugolix are greater than the possible hazards 1. Where feasible, do not use relugolix alongside QT prolonging drugs. When coadministration cannot be avoided, refrain from using agents 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
What your care team may do:
- Decide whether the benefit of relugolix outweighs the risk, particularly if you have long QT syndrome, heart failure, or frequent electrolyte problems.
- Where possible, choose an alternative to avoid combining QT prolonging drugs.
- If both are needed, monitor your ECG and blood electrolytes (potassium and magnesium) periodically and correct any that are low.
What you should do: Keep taking both as prescribed unless told otherwise. Tell your pharmacist or doctor about any dizziness, fainting, or palpitations, 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 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% 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 raise TdP risk; nevertheless, exposure to 1 drug and to 2 or more drugs carrying conditional, possible, or known TdP risk was documented 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 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 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 receiving ADT chiefly for prostate cancer, with some 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 Protriptyline together?
Combining protriptyline and relugolix can add up their effects on your heart rhythm (QT interval); 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 Protriptyline 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 Protriptyline interaction managed?
What your care team may do: Decide whether the benefit of relugolix outweighs the risk, particularly if you have long QT syndrome, heart failure, or frequent electrolyte problems. Where possible, choose an alternative to avoid combining QT prolonging drugs. If both are needed, monitor your ECG and blood electrolytes (potassium and magnesium) periodically and correct any that are low. What you shou… 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 Protriptyline 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 Protriptyline
Keep reading about Relugolix
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