Encorafenib and Gepirone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Gepirone
Encorafenib
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.
What happens
Reduced gepirone exposure; reduced efficacy of gepirone, an increased risk of QT interval prolongation and cardiac arrhythmias
Interaction Deep Dive
void the coadministration of encorafenib (strong CYP3A4 inducer) with gepirone (sensitive CYP3A4 substrate) as it may reduce gepirone exposure and may also reduce efficacy of gepirone1. Coadministration of gepirone with other drugs that prolong the QT interval may increase the risk of QT interval prolongation and may increase the risk of cardiac arrhythmias. Monitor patients with electrocardiograms more frequently if gepirone is used concomitantly with other drugs that are known to prolong QT interval 2. Correct hypokalemia and hypomagnesemia prior to and during encorafenib administration. Withhold encorafenib until QTcF less than or equal to 500 ms, resume at reduced dose. If more than one recurrence, permanently discontinue encorafenib. Also, permanently discontinue encorafenib for QTcF more than 500 ms. In a drug interaction study, repeat dose administration of encorafenib 450 mg once daily and binimetinib 45 mg twice daily with a single dose of midazolam 2 mg, a sensitive CYP3A4 substrate, decreased midazolam AUC by 82% and Cmax by 74% relative to midazolam 2 mg alone 1.
Why it happens (mechanism)
Induction of CYP3A4-substrate metabolism by encorafenib; additive QT interval prolongation
Literature reports
1 report — tap to read
a) In a drug interaction study, repeat dose administration of encorafenib 450 mg once daily and binimetinib 45 mg twice daily with a single dose of midazolam 2 mg, a sensitive CYP3A4 substrate, decreased midazolam AUC by 82% and Cmax by 74% relative to midazolam 2 mg alone 1.
Common questions
Can I take Encorafenib and Gepirone together?
Reduced gepirone exposure; reduced efficacy of gepirone, an increased risk of QT interval prolongation and cardiac arrhythmias Always confirm with your pharmacist or prescriber before making any change.
How serious is the Encorafenib and Gepirone 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 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 Encorafenib or Gepirone 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 (2)
- Product Information: BRAFTOVI(R) oral capsules, encorafenib oral capsules. Array BioPharma Inc (per FDA), Boulder, CO, 2024. DailyMed
- Product Information: EXXUA extended-release oral tablets, gepirone extended-release oral tablets. Mission Pharmaceutical Company (per FDA), San Antonio, TX, 2023. DailyMed
Keep reading about Gepirone
Keep reading about Encorafenib
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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