Encorafenib and Ketoconazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole
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
Increased encorafenib exposure, an increased risk of encorafenib-related adverse events and an increased risk of QT interval prolongation,
Interaction Deep Dive
Coadministration of ketoconazole (a strong CYP3A4 inhibitor that may prolong the QT interval) with CYP3A4 substrates that are known to prolong the QT interval, such as encorafenib is contraindicated as it may cause increased encorafenib exposure, increasing the risk for QT interval prolongation and result in life-threatening ventricular tachyarrhythmias such as torsade de pointes2. If coadministration cannot be avoided, reduce the encorafenib dose. If the current encorafenib dose is 450 mg/day, reduce to 150 mg/day and if it is 300, 225, or 150 mg/day, reduce to 75 mg/day. Note that encorafenib exposure with 75 mg/day when coadministered with a strong CYP3A4 inhibitor is expected to be higher than at the 150 mg/day dosage in the absence of a CYP3A4 inhibitor and similar to exposure at the 225 mg/day dosage in the absence of a CYP3A4 inhibitor 1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated encorafenib metabolism by ketoconazole; additive QT interval prolongation;
Literature reports
1 report — tap to read
a) In a drug interaction study, coadministration of posaconazole (a strong CYP3A4 inhibitor) with encorafenib increased the AUC of encorafenib by 3-fold and increased the Cmax by 68% following a single dose of encorafenib 50 mg (0.1 times the usual dose) 1.
Common questions
Can I take Encorafenib and Ketoconazole together?
Increased encorafenib exposure, an increased risk of encorafenib-related adverse events 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 Ketoconazole interaction?
It is rated contraindicated. These should generally not be used together.
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 Ketoconazole 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 Ketoconazole
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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