Encorafenib and Entrectinib: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Encorafenib
Entrectinib
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 entrectinib exposure, reduced efficacy of entrectinib and an increased risk of QT interval prolongation
Interaction Deep Dive
Avoid concomitant use of drugs that prolong the QTc or QT interval as it may add to the QTc or QT effects of entrectinib and increase the risk of cardiac arrhythmias. If concomitant use cannot be avoided, assess QT interval and electrolytes prior to initiation of entrectinib and periodically during treatment. Based on the severity of QTc interval prolongation, withhold entrectinib and then resume at same or reduced dose, or permanently discontinue1. Encorafenib is associated with dose-dependent QTc interval prolongation. Monitor patients who already have or who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure and those taking other medicinal products associated with QT prolongation. Correct hypokalemia and hypomagnesemia prior to and during encorafenib administration. Withhold encorafenib until QTcF (QT interval corrected per Fridericia formula) 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. Coadministration of encorafenib with entrectinib (sensitive CYP3A4 substrate) may also reduce entrectinib exposure and may reduce efficacy of entrectinib 2.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of entrectinib; 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 2.
Common questions
Can I take Encorafenib and Entrectinib together?
Reduced entrectinib exposure, reduced efficacy of entrectinib and an increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Encorafenib and Entrectinib 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 Entrectinib 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)
Keep reading about Encorafenib
Keep reading about Entrectinib
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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