Lefamulin and Flibanserin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Flibanserin
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 flibanserin exposure and an increased risk of flibanserin-related toxicities associated with cardiac conduction
Interaction Deep Dive
Avoid concomitant use of oral lefamulin with a P-gp inhibitor such as flibanserin as it may increase lefamulin exposure, which may increase the risk of lefamulin adverse effects. Concomitant administration of oral lefamulin with a sensitive CYP3A4 substrate such as flibanserin may result in increased flibanserin exposure, increasing the risk of adverse effects; monitor for flibanserin adverse effects, if used concomitantly with lefamulin. In a drug interaction study, oral ketoconazole (strong CYP3A4/P-gp inhibitor) increased the lefamulin AUC and Cmax by 165% and 58%, respectively, when administered concomitantly with oral lefamulin. In an another drug interaction study, mean AUC and Cmax of midazolam (sensitive CYP3A 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-mediated metabolism of flibanserin
Literature reports
2 reports — tap to read
a) In a drug interaction study, oral ketoconazole (a strong CYP3A4/P-gp inhibitor) increased the mean lefamulin AUC(0 to inf) and Cmax by 31% and 6%, respectively, when administered concomitantly with IV lefamulin. Additionally, oral ketoconazole increased the lefamulin AUC(0 to inf) and Cmax by 165% and 58%, respectively, when administered concomitantly with oral lefamulin 1.
b) Mean AUC and Cmax of midazolam (a 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 Lefamulin and Flibanserin together?
Increased lefamulin exposure, an increased risk of lefamulin-related adverse reactions, increased flibanserin exposure and an increased risk of flibanserin-related toxicities associated with cardiac conduction Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lefamulin and Flibanserin 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 Lefamulin or Flibanserin 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 Flibanserin
Keep reading about Lefamulin
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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