Relugolix and Donepezil: 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
Donepezil
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 electrical rhythm in the same direction. Donepezil (used for memory) and relugolix (used for prostate cancer, by lowering testosterone) can each 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.
The good news is that this is a theoretical concern, and your care team can manage it. They may check an ECG (a heart tracing) and your blood levels of potassium and magnesium. Keep taking both as prescribed, and let your pharmacist or doctor know if you feel faint, dizzy, or have a fluttering heartbeat.
Additive QT prolongation. Both agents independently prolong the QT interval (donepezil via a recognized QT effect; relugolix via androgen deprivation), producing a pharmacodynamic, additive interaction rather than a metabolic one. Neither is a prodrug relevant here.
- Direction: increased combined QT prolongation and torsades risk.
- Evidence: theoretical; severity: major; onset unspecified.
- Higher-risk patients: congenital long QT, CHF, frequent electrolyte disturbances.
- Management: avoid concomitant use when possible; if required, avoid drugs causing hypokalemia/hypomagnesemia, correct electrolytes, 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. GnRH agonists and antagonists can lengthen the QT interval through the androgen deprivation they produce. 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 agents. Should coadministration be necessary, steer clear of drugs that produce electrolyte disturbances (namely, hypokalemia or hypomagnesemia) 2, rectify any electrolyte abnormalities, and think about periodic ECG and electrolyte monitoring 1.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
This can usually be managed by your care team. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your team may weigh whether the benefits of relugolix outweigh the risk, especially if you have a heart rhythm condition, heart failure, or frequent electrolyte problems.
- They may check periodic ECGs and blood electrolytes (potassium and magnesium), correcting any low levels.
- Tell your doctor or pharmacist about all your medicines, including anything else that affects heart rhythm.
- Report fainting, dizziness, or palpitations promptly.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A study assessed male patients undergoing androgen deprivation therapy (ADT) using individual case safety reports from VigiBase, the international pharmacovigilance database. It 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%) tied to ADT occurred in the absence of other agents known to elevate TdP risk; nevertheless, 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 showed 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%); 17% were receiving ADT combination therapy 3.
Common questions
Can I take Relugolix and Donepezil together?
Taking donepezil and relugolix together can add up their effects on your heart rhythm (QT interval), so your care team may monitor your ECG and electrolytes. Keep taking both as prescribed and report any dizziness, fainting, or palpitations. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Donepezil 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 Donepezil interaction managed?
This can usually be managed by your care team. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your team may weigh whether the benefits of relugolix outweigh the risk, especially if you have a heart rhythm condition, heart failure, or frequent electrolyte problems. They may check periodic ECGs and blood electrolytes (potassium and magnesium), correcting… 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 Donepezil 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 Donepezil
Keep reading about Relugolix
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