Isavuconazonium and Lefamulin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Isavuconazonium
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 and an increased risk of lefamulin-related adverse reactions and increased isavuconazonium exposure and an increased risk of isavuconazonium-related toxicities
Interaction Deep Dive
Avoid concomitant use of oral lefamulin with isavuconazonium (a strong and moderate CYP3A4 and P-gp inhibitor) as it may increase lefamulin exposure, which may increase the risk of adverse reactions with lefamulin. In addition, concomitant administration of oral lefamulin with isavuconazonium (a sensitive CYP3A4 substrate) may result in increased exposure of isavuconazonium, increasing the risk of adverse effects. Monitor for adverse effects of these agents when used with lefamulin oral tablets. Oral ketoconazole (a strong CYP3A/P-gp inhibitor) increased the mean lefamulin AUC and Cmax by 31% and 6%, respectively, when administered concomitantly with IV lefamulin. Additionally, oral ketoconazole (strong inhibitor) increased the lefamulin AUC and Cmax by 165% and 58%, respectively, when administered concomitantly with oral lefamulin. In a 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 lefamulin oral tablets1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of lefamulin; inhibition of P-gp-mediated efflux transport of lefamulin; and inhibition of CYP3A4-mediated metabolism by lefamulin
Literature reports
2 reports — tap to read
a) 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 (strong inhibitor) increased the lefamulin AUC(0 to inf) and Cmax by 165% and 58%, respectively, when administered concomitantly with oral lefamulin 1.
b) In a 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 lefamulin oral tablets 1.
Common questions
Can I take Isavuconazonium and Lefamulin together?
Increased lefamulin exposure and an increased risk of lefamulin-related adverse reactions and increased isavuconazonium exposure and an increased risk of isavuconazonium-related toxicities Always confirm with your pharmacist or prescriber before making any change.
How serious is the Isavuconazonium 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 Isavuconazonium 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 Isavuconazonium
Keep reading about Lefamulin
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist