Siponimod and Relugolix: 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
Siponimod
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 siponimod (Mayzent) and relugolix (Orgovyx) can affect your heart's electrical rhythm in the same way. Each one can stretch out a part of your heartbeat called the QT interval. When you take them together, that effect can add up, which slightly raises the chance of an irregular heartbeat.
The good news is this is a theoretical concern, and your care team can manage it well. They may check an ECG (heart tracing) and your blood minerals like potassium and magnesium now and then. Please keep taking both as prescribed, and let your doctor or pharmacist know if you feel dizzy, faint, or notice a fluttering heartbeat.
Interaction: Additive QT prolongation with concurrent siponimod and relugolix. Both agents are independently associated with QTc prolongation; relugolix-induced androgen deprivation and siponimod's cardiac effects contribute additively (pharmacodynamic, not enzyme-mediated). Neither is a QT-relevant prodrug here.
- Direction: Increased QT prolongation / torsades risk.
- Evidence: Theoretical; severity rated major.
- Onset: Unspecified.
- Management: Avoid combination when possible. Weigh benefit vs risk in congenital long QT, CHF, or recurrent electrolyte disturbance. If coadministered, avoid drugs causing hypokalemia/hypomagnesemia, correct electrolytes, and obtain 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 or 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 to prolong the QT interval, weigh whether the benefits of androgen deprivation therapy such as relugolix are greater than the possible risks 1. Where feasible, do not use relugolix at the same time as agents that prolong the QT interval. When such coadministration cannot be avoided, refrain from using drugs that produce electrolyte abnormalities (ie, 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
Your care team knows how to handle this safely. Typical steps include:
- Weighing benefits vs risks if you have a congenital long QT syndrome, heart failure, or frequent electrolyte problems.
- Checking electrolytes (potassium and magnesium) and correcting any low levels, since these raise QT risk.
- Periodic ECGs and blood tests to keep an eye on your heart rhythm.
- Avoiding other medicines that lower potassium or magnesium when possible.
Keep taking both medications exactly as prescribed. Ask your pharmacist or prescriber before adding any new drug, and report fainting, palpitations, or severe dizziness right away.
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 on 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 cases 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 concurrent use of other agents recognized to elevate TdP risk; nevertheless, use of 1 drug and 2 or more drugs carrying conditional, possible, or known TdP risk was noted in a portion of aLQTS/TdP events (23% or 43%) and sudden death events (18% and 22%). The agents classified 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 taking ADT chiefly for prostate cancer, with some being treated for prostatism and androgenic alopecia. The majority of patients received ADT monotherapy (83%); 17% were on ADT combination therapy 3.
Common questions
Can I take Siponimod and Relugolix together?
Taking siponimod and relugolix together can add up to prolong the QT interval, so your doctor may monitor your heart rhythm and electrolytes. Keep taking both as prescribed and report any fainting or palpitations. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Siponimod and Relugolix 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 Siponimod and Relugolix interaction managed?
Your care team knows how to handle this safely. Typical steps include: Weighing benefits vs risks if you have a congenital long QT syndrome, heart failure, or frequent electrolyte problems. Checking electrolytes (potassium and magnesium) and correcting any low levels, since these raise QT risk. Periodic ECGs and blood tests to keep an eye on your heart rhythm. Avoiding other medicines that lower p… 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 Siponimod or Relugolix 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 Siponimod
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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