Relugolix and Methadone: 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
Methadone
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. Methadone is well known for slowing down the heart's electrical reset, something doctors call QT prolongation. Relugolix, which lowers testosterone to treat prostate cancer, can also nudge the QT in that same direction. When you take them together, those effects can add up, and in rare cases an unusually long QT can lead to a dangerous heartbeat.
The good news is this is manageable. Right now this concern is based more on how the drugs work than on lots of real-world cases. Your care team can keep an eye on your heart tracing (ECG) and blood minerals like potassium and magnesium. Please don't stop either medicine on your own, just talk with your pharmacist or doctor.
Effect: Additive QT-interval prolongation with concurrent methadone and relugolix.
- Mechanism: Pharmacodynamic (additive), not PK. Methadone blocks the hERG/IKr potassium current; androgen deprivation from relugolix independently prolongs QT. Neither is a prodrug here.
- Direction: Increased combined QT effect and torsades risk.
- Evidence: Theoretical; onset unspecified. Severity major.
- Management: Avoid combination when feasible. If coadministered, correct and maintain K+ and Mg2+, avoid additional QT-prolonging or electrolyte-depleting agents, and obtain periodic ECG and electrolyte monitoring. Weigh ADT benefit against risk in congenital long QT, CHF, or recurrent electrolyte disturbance.
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 benefits of androgen deprivation therapy such as relugolix outweigh the possible risks 1. Where feasible, do not use relugolix concurrently with QT prolonging agents. Should coadministration be necessary, refrain from using medications that produce electrolyte disturbances (such as 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
Keep taking both medicines as prescribed unless your care team tells you otherwise. Because both can add to QT prolongation, your team manages this with monitoring rather than automatic changes.
- Your prescriber may order periodic ECGs and blood tests for potassium and magnesium.
- Low potassium or magnesium raises the risk, so your team will correct and keep those levels normal.
- Tell your team if you have fainting, dizziness, or a pounding or irregular heartbeat.
- Mention any heart-rhythm history, heart failure, or other QT-affecting drugs or supplements.
Your care team can tailor monitoring and, when possible, choose alternatives to keep you safe.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In an analysis of male patients undergoing androgen deprivation therapy (ADT) using individual case safety reports from VigiBase, the international pharmacovigilance database, investigators 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%) associated with ADT arose without concurrent use of other agents known 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 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 used for prostate cancer, and 5-alpha-reductase inhibitors used 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 from initiation to aLQTS/TdP events was 170 days (range, 7 to 4884 days) while for sudden death events it was 92 days (range, 0.25 to 4984 days). Patients were primarily receiving ADT 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 Methadone together?
Methadone and relugolix can each stretch the heart's QT interval, and together the risk adds up, so avoid the combination when possible and let your care team monitor your ECG and electrolytes if you take both. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Methadone 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 Methadone interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. Because both can add to QT prolongation, your team manages this with monitoring rather than automatic changes. Your prescriber may order periodic ECGs and blood tests for potassium and magnesium. Low potassium or magnesium raises the risk, so your team will correct and keep those levels normal. Tell your team if yo… 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 Methadone 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 Methadone
Keep reading about Relugolix
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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