Encorafenib and Lonafarnib: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Lonafarnib
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
An increased risk of QT interval prolongation and torsade de pointes, increased encorafenib exposure and an increased risk of encorafenib-related adverse events
Interaction Deep Dive
Avoid concomitant use of lonafarnib (QTc prolonging agent) with other products that prolong the QTc interval, such as encorafenib as it may result in a greater increase of the QTc interval and adverse reactions associated with QTc interval prolongation, including torsade de pointes, other serious arrhythmias, and sudden death. If concomitant use cannot be avoided, monitor ECGs when initiating, during concomitant use2. Concomitant use of encorafenib (moderate CYP3A4 substrate) with lonafarnib (strong CYP3A4 inhibitors) may also increase encorafenib exposure an increased 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 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 lonafarnib is expected to be higher than at the 150 mg/day dosage in the absence of lonafarnib and similar to exposure at the 225 mg/day dosage in the absence of lonafarnib. Monitor patients closely for adverse reactions and use clinical judgement when using encorafenib 150 mg/day with lonafarnib. After lonafarnib has been discontinued for 3 to 5 elimination half-lives, resume the encorafenib dose that was taken prior to initiating lonafarnib 1.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of CYP3A4-mediated encorafenib metabolism
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 Lonafarnib together?
An increased risk of QT interval prolongation and torsade de pointes, increased encorafenib exposure and an increased risk of encorafenib-related adverse events Always confirm with your pharmacist or prescriber before making any change.
How serious is the Encorafenib and Lonafarnib 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 Lonafarnib 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 Lonafarnib
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist