Entrectinib and Lefamulin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Entrectinib
Lefamulin
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 lefamulin exposure, an increased risk of lefamulin-related adverse reactions, increased entrectinib exposure, an increased risk of entrectinib-related toxicities associated with cardiac conduction and an increased risk of QT interval prolongatio
Interaction Deep Dive
Oral lefamulin is contraindicated with sensitive CYP3A4 substrates that are P-gp inhibitors and that prolong the QT interval, such as entrectinib. Concomitant administration of oral lefamulin with entrectinib may result in increased entrectinib exposure, leading to QT prolongation and cases of torsades de pointes. Concomitant use of lefamulin injection with entrectinib does not affect the exposure of entrectinib. Concomitant use may also increase lefamulin exposure and may increase risk of lefamulin-related adverse reactions. In a drug interaction study, mean AUC(0 to inf) and Cmax of midazolam were increased by approximately 200% and 100%, respectively, when oral midazolam (sensitive CYP3A4 substrate) was administered concomitantly with and at 2 or 4 hours after administration of lefamulin oral tablets1. 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 discontinue 2.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of lefamulin; inhibition of CYP3A4-substrate metabolism of entrectinib; additive QT interval prolongation
Literature reports
1 report — tap to read
a) In a drug interaction study, mean AUC(0 to inf) and Cmax of midazolam were increased by approximately 200% and 100%, respectively, when oral midazolam (sensitive CYP3A4 substrate) was administered concomitantly with and at 2 or 4 hours after administration of lefamulin oral tablets 1.
Common questions
Can I take Entrectinib and Lefamulin together?
Increased lefamulin exposure, an increased risk of lefamulin-related adverse reactions, increased entrectinib exposure, an increased risk of entrectinib-related toxicities associated with cardiac conduction and an increased risk of QT interval prolongatio Always confirm with your pharmacist or prescriber before making any change.
How serious is the Entrectinib and Lefamulin 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 Entrectinib or Lefamulin 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)
- Product Information: XENLETA(R) oral tablets, intravenous injection, lefamulin oral tablets, intravenous injection. Nabriva Therapeutics US Inc (per FDA), King of Prussia, PA, 2021. DailyMed
- Product Information: ROZLYTREK(R) oral capsules, pellets, entrectinib oral capsules, pellets. Genentech Inc (per FDA), South San Francisco, CA, 2023. DailyMed
Keep reading about Entrectinib
Keep reading about Lefamulin
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