Relugolix and Papaverine: 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
Papaverine
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 two medicines, relugolix (Orgovyx) and papaverine, that can each affect your heart's rhythm. Both can lengthen a part of your heartbeat called the QT interval. When two medicines do this at the same time, the effect can add up, and in rare cases that can lead to an irregular heartbeat.
Please don't stop either medicine on your own. This is something your care team knows how to handle. They may check an ECG (heart tracing) and your blood minerals like potassium and magnesium from time to time. Let your doctor or pharmacist know if you feel dizzy, faint, or notice a fluttering heartbeat.
Effect: Additive QT-interval prolongation with coadministration of relugolix and papaverine. Neither is a prodrug; this is a pharmacodynamic (PD), not metabolic, interaction.
Direction/mechanism: Both agents can prolong the QT interval; relugolix-associated androgen deprivation itself may prolong QT, giving additive risk of torsades de pointes.
Evidence: Theoretical. Onset: unspecified. Severity: major.
Management:
- Avoid concomitant use where possible; weigh benefits of ADT against risk.
- Higher caution in congenital long QT, CHF, or recurrent electrolyte disturbance.
- Correct and maintain K+ and Mg2+; avoid agents causing hypokalemia/hypomagnesemia.
- 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 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 alongside QT prolonging agents. Should coadministration be necessary, refrain from using medications that produce electrolyte disturbances (that is, 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 exactly as prescribed unless your doctor tells you otherwise. Because both can lengthen the QT interval, your care team may take steps to keep you safe.
- They may check periodic ECGs and blood electrolytes (potassium and magnesium).
- They will correct any low potassium or magnesium and try to avoid medicines that cause those drops.
- Where possible, they may consider whether an alternative to one of the drugs is appropriate.
Tell your pharmacist or prescriber if you have a history of heart rhythm problems, heart failure, or fainting, and report any dizziness, palpitations, or fainting right away.
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 were fatal), along with 99 cases of sudden death linked to ADT. The majority of aLQTS/TdP cases (62%) and sudden death cases (88%) tied to ADT arose without exposure to other agents recognized to raise TdP risk; nevertheless, some aLQTS/TdP events (23% with 1 drug or 43% with 2 or more drugs) and sudden death events (18% and 22%) involved exposure to one drug and two or more drugs carrying conditional, possible, or known TdP risk. 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 evaluated, 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 primarily receiving ADT for prostate cancer, with some treated for prostatism and androgenic alopecia. Most patients were on ADT monotherapy (83%), while 17% were receiving ADT combination therapy 3.
Common questions
Can I take Relugolix and Papaverine together?
Relugolix and papaverine can each prolong the QT interval, so together they may add up and raise the risk of an abnormal heart rhythm. Take 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 Papaverine 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 Papaverine interaction managed?
Keep taking both medicines exactly as prescribed unless your doctor tells you otherwise. Because both can lengthen the QT interval, your care team may take steps to keep you safe. They may check periodic ECGs and blood electrolytes (potassium and magnesium). They will correct any low potassium or magnesium and try to avoid medicines that cause those drops. Where possible, they may consider whether… 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 Papaverine 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 Papaverine
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