Lefamulin and Repotrectinib: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Lefamulin
Repotrectinib
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
Reduced lefamulin exposure, reduced efficacy of lefamulin, an increased repotrectinib exposure and an increased risk of repotrectinib-related toxicities associated with cardiac conduction
Interaction Deep Dive
Concomitant use of oral lefamulin with repotrectinib (sensitive CYP3A4 substrate) is contraindicated as it may increase repotrectinib exposure and may increase repotrectinib-related toxicities associated with cardiac conduction. Concomitant use of lefamulin injection with repotrectinib does not affect the exposure of repotrectinib. Coadministration of lefamulin and repotrectinib (moderate CYP3A4 inducer) may also reduce lefamulin exposure and may reduce efficacy of lefamulin. 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 oral lefamulin1.
Why it happens (mechanism)
Induction of CYP3A4-mediated lefamulin metabolism; inhibition of CYP3A4-mediated metabolism of repotrectinib
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 CYP3A substrate) was administered concomitantly with and at 2 or 4 hours after administration of lefamulin oral tablets 1.
Common questions
Can I take Lefamulin and Repotrectinib together?
Reduced lefamulin exposure, reduced efficacy of lefamulin, an increased repotrectinib exposure and an increased risk of repotrectinib-related toxicities associated with cardiac conduction Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lefamulin and Repotrectinib 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 Lefamulin or Repotrectinib 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: XENLETA(R) oral tablets, intravenous injection, lefamulin oral tablets, intravenous injection. Nabriva Therapeutics US Inc (per FDA), King of Prussia, PA, 2021. DailyMed
Keep reading about Lefamulin
Keep reading about Repotrectinib
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