Relugolix and Perphenazine: 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
Perphenazine
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.
You've been prescribed two medicines that can each affect your heart's rhythm. Perphenazine (an older antipsychotic) and relugolix (Orgovyx, used for prostate cancer) can both stretch out a part of your heartbeat called the QT interval. When taken together, that effect can add up and, in rare cases, lead to an irregular heartbeat.
The good news is this is a known, manageable concern. Your care team can keep an eye on things with occasional heart tracings (ECGs) and blood tests, and make sure your minerals like potassium and magnesium stay in a healthy range. Please keep taking both medicines as prescribed, and talk with your pharmacist or doctor about any dizziness, fainting, or fluttering in your chest.
Effect: Additive QT interval prolongation with combined perphenazine (phenothiazine antipsychotic) and relugolix (GnRH receptor antagonist). Androgen deprivation itself may prolong QTc.
Direction/mechanism: Additive pharmacodynamic effect on cardiac repolarization; not a metabolic (PK) interaction. Neither is a prodrug relevant here.
Evidence: Theoretical. Severity: Major. Onset: Unspecified.
Management:
- Avoid concomitant use where possible; weigh benefits of ADT against risk.
- Higher caution with congenital long QT, CHF, or electrolyte disturbances.
- Correct and avoid 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 are greater than the possible hazards 1. Where feasible, do not use relugolix alongside QT prolonging agents. Should combined use be necessary, refrain from using medications that produce electrolyte disturbances (that is, 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
This combination is manageable with attention from your care team. Because both drugs can affect heart rhythm, your team may:
- Decide whether you truly need both, or whether an alternative is appropriate for you.
- Check periodic ECGs (heart tracings) and blood electrolytes.
- Keep your potassium and magnesium levels in a healthy range and correct them if low.
What you should do: Keep taking both medicines exactly as prescribed unless told otherwise. Tell your pharmacist or doctor about any fainting, dizziness, or palpitations, and mention any other QT-affecting drugs, water pills, or vomiting/diarrhea that could lower your electrolytes.
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 found 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 raise TdP risk; nevertheless, use of 1 drug and of 2 or more drugs carrying conditional, possible, or known TdP risk was documented in a portion of aLQTS/TdP (23% or 43%) and sudden death (18% and 22%) events. 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 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 principally receiving ADT for prostate cancer, with some treated for prostatism and androgenic alopecia. Most patients received ADT as monotherapy (83%); 17% were on ADT combination therapy 3.
Common questions
Can I take Relugolix and Perphenazine together?
Perphenazine and relugolix can both prolong the QT interval, and together the effect may add up. Keep taking both as prescribed, but let your care team monitor your ECG and electrolytes and report any fainting or palpitations. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Perphenazine 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 Perphenazine interaction managed?
This combination is manageable with attention from your care team. Because both drugs can affect heart rhythm, your team may: Decide whether you truly need both, or whether an alternative is appropriate for you. Check periodic ECGs (heart tracings) and blood electrolytes. Keep your potassium and magnesium levels in a healthy range and correct them if low. What you should do: Keep taking both medic… 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 Perphenazine 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 Perphenazine
Keep reading about Relugolix
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