Lefamulin and Mifepristone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Mifepristone
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 miFEPRIStone exposure, and an increased risk of QT interval prolongation
Interaction Deep Dive
Avoid concomitant use of lefamulin with strong CYP3A/P-gp inhibitors that prolong the QT interval as it may increase lefamulin exposure and may increase the risk of adverse reactions with lefamulin, including QT prolongation. Lefamulin (oral/IV) has the potential to prolong the QT interval in some patients. ECG monitoring is recommended if coadministration cannot be avoided. The magnitude of QT prolongation may increase with increasing concentration of lefamulin or increasing the rate of infusion of the IV formulation. Therefore, do not exceed recommended dose and infusion rate1. Use extreme caution when miFEPRIStone is coadministered with drugs that have high first pass metabolism via CYP3A. Use the lowest dose and/or decreased frequency with therapeutic monitoring. Prefer alternative drugs without these metabolic characteristics when possible. Coadministration of miFEPRIStone and CYP3A inhibitors may also increase miFEPRIStone exposure. MiFEPRIStone and its metabolites block IKr. MiFEPRIStone prolongs the QTc interval in a dose related manner. There is little or no experience with high exposure, concomitant dosing with other QT prolonging drugs, or potassium channel variants resulting in a long QT interval. Carefully weigh the benefit of concomitant use of these agents against the potential risks. Limit the dose of miFEPRIStone to 900 mg. Additionally, wait at least 2 weeks after stopping miFEPRIStone before initiating lefamulin 2.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of lefamulin; inhibition of CYP3A-mediated metabolism of lefamulin; inhibition of CYP3A-mediated metabolism of miFEPRIStone; additive QT prolongation
Literature reports
1 report — tap to read
a) In a drug interaction study, oral ketoconazole (a strong CYP3A/P-gp inhibitor) increased the mean lefamulin AUC(0 to infinity) and Cmax by 31% and 6%, respectively, when administered concomitantly with IV lefamulin. Additionally, oral ketoconazole (strong inhibitor) increased the lefamulin AUC(0 to inf) and Cmax by 165% and 58%, respectively, when administered concomitantly with oral lefamulin 1.
Common questions
Can I take Lefamulin and Mifepristone together?
Increased lefamulin exposure, an increased miFEPRIStone exposure, and an increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lefamulin and Mifepristone 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 Mifepristone 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: KORLYM(R) oral tablets, mifepristone oral tablets. Corcept Therapeutics Incorporated (per Dailmed), Redwood City, CA, 2024. DailyMed
Keep reading about Mifepristone
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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