Aprepitant and Encorafenib: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Aprepitant
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 reactions, reduced sensitive CYP3A4 substrate exposure and reduced efficacy of sensitive CYP3A4 substrates
Interaction Deep Dive
Avoid concomitant administration of encorafenib with a sensitive CYP3A4 substrates that are moderate CYP3A4 inhibitor as it may increase encorafenib exposure and may increase risk of encorafenib-related adverse reactions. Concomitant use may also reduce sensitive CYP3A4 substrates exposure and may reduce efficacy of sensitive CYP3A4 substrates. If coadministration cannot be avoided, reduce the encorafenib dose. If the current encorafenib dose is 450 mg/day, reduce to 225 mg/day, if the current dose is 300 mg/day, reduce to 150 mg/day, and if the current dose is 225 or 150 mg/day, reduce to 75 mg/day. After the CYP3A4 inhibitor has been discontinued for 3 to 5 elimination half-lives, resume the encorafenib dose that was taken prior to initiating the CYP3A4 inhibitor. In a drug interaction study, coadministration of dilTIAZem (a moderate CYP3A4 inhibitor) with encorafenib increased the AUC of encorafenib by 2-fold and increased the Cmax by 45% following a single dose of encorafenib 50 mg (0.1 times the usual dose). In another 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 alone1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated encorafenib metabolism; induction of CYP3A4-substrate metabolism by encorafenib
Literature reports
2 reports — tap to read
a) In a drug interaction study, coadministration of dilTIAZem (a moderate CYP3A4 inhibitor) with encorafenib increased the AUC of encorafenib by 2-fold and increased the Cmax by 45% following a single dose of encorafenib 50 mg (0.1 times the usual dose) 1.
b) 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 Aprepitant and Encorafenib together?
Increased encorafenib exposure, an increased risk of encorafenib-related adverse reactions, reduced sensitive CYP3A4 substrate exposure and reduced efficacy of sensitive CYP3A4 substrates Always confirm with your pharmacist or prescriber before making any change.
How serious is the Aprepitant and Encorafenib 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Aprepitant or Encorafenib 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 (1)
- Product Information: BRAFTOVI(R) oral capsules, encorafenib oral capsules. Array BioPharma Inc (per FDA), Boulder, CO, 2024. DailyMed
Keep reading about Aprepitant
Keep reading about Encorafenib
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