Dronedarone and Lefamulin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Dronedarone
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, an increased dronedarone exposure, an increased risk of dronedarone-related toxicities associated with cardiac conduction and an increased risk of QT interval prolonga
Interaction Deep Dive
Oral lefamulin is contraindicated with sensitive CYP3A4 substrates that prolong the QT interval, including dronedarone. Concomitant administration of oral lefamulin with dronedarone may result in increased dronedarone exposure, leading to QT prolongation and cases of torsades de pointes. Concomitant use of oral lefamulin with dronedarone (P-gp inhibitor) may also increase risk of lefamulin exposure resulting in lefamulin-related adverse reactions1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated dronedarone metabolism; inhibition of CYP3A4-mediated lefamulin metabolism; additive QT interval prolongation; inhibition of P-gp-mediated efflux transport of lefamulin
Literature reports
1 report — tap to read
a) In a drug 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 Dronedarone and Lefamulin together?
Increased lefamulin exposure, an increased risk of lefamulin-related adverse reactions, an increased dronedarone exposure, an increased risk of dronedarone-related toxicities associated with cardiac conduction and an increased risk of QT interval prolonga Always confirm with your pharmacist or prescriber before making any change.
How serious is the Dronedarone 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 Dronedarone 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
Keep reading about Dronedarone
Keep reading about Lefamulin
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