Neratinib and Lefamulin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Neratinib
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 and increased sensitive CYP3A4 substrate exposure
Interaction Deep Dive
Avoid concomitant use of lefamulin with P-gp inhibitors, as it may increase lefamulin exposure and may also increase risk of lefamulin-related adverse reactions. Concomitant administration of oral lefamulin with sensitive CYP3A4 substrates may result in increased exposure of these drugs, increasing the risk of adverse effects; monitor for adverse effects of these agents when used with oral lefamulin. In a drug interaction study, mean AUC and Cmax of midazolam (sensitive CYP3A4 substrate) were increased by approximately 200% and 100%, respectively, when oral midazolam was administered concomitantly with and at 2 or 4 hours after administration of oral lefamulin1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of lefamulin; inhibition of CYP3A4-substrate metabolism by lefamulin
Literature reports
1 report — tap to read
a) In a drug interaction study, mean AUC and Cmax of midazolam (sensitive CYP3A4 substrate) were increased by approximately 200% and 100%, respectively, when oral midazolam was administered concomitantly with and at 2 or 4 hours after administration of oral lefamulin 1.
Common questions
Can I take Neratinib and Lefamulin together?
Increased lefamulin exposure, an increased risk of lefamulin-related adverse reactions and increased sensitive CYP3A4 substrate exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Neratinib and Lefamulin 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 Neratinib 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 (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
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