Encorafenib and Isavuconazonium: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Isavuconazonium
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 and an increased risk of encorafenib-related adverse events; reduced CYP3A4 substrate exposure and reduced efficacy of CYP3A4 substrate
Interaction Deep Dive
Avoid concomitant administration of encorafenib with isavuconazonium sulfate (prodrug of isavuconazole and moderate CYP3A4 inhibitor) as it may increase encorafenib exposure and may also increase risk of encorafenib-related adverse reactions. 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 addition, avoid the coadministration of encorafenib (strong CYP3A4 inducer) with isavuconazonium sulfate (a prodrug of isavuconazole and a sensitive CYP3A4 substrate) as it may reduce isavuconazole exposure and may also reduce efficacy of isavuconazole. 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. In another 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.
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, 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.
b) 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.
Common questions
Can I take Encorafenib and Isavuconazonium together?
Increased encorafenib exposure and an increased risk of encorafenib-related adverse events; reduced CYP3A4 substrate exposure and reduced efficacy of CYP3A4 substrate Always confirm with your pharmacist or prescriber before making any change.
How serious is the Encorafenib and Isavuconazonium 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 Encorafenib or Isavuconazonium 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 Isavuconazonium
Keep reading about Encorafenib
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