Drug Interaction Report

Lefamulin and Gepirone: Interaction Details

A pharmacist-reviewed analysis of the Lefamulin and Gepirone interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Gepirone

Exxua
+

Lefamulin

Xenleta Xenleta®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 443 documented Lefamulin interactions, 402 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

Increased gepirone exposure and an increased risk of gepirone-related toxicities, an increased risk of QT interval prolongation and cardiac arrhythmias

Interaction Deep Dive

Concomitant administration of oral lefamulin with gepirone (sensitive CYP3A4 substrate) may result in increased gepirone exposure, increasing the risk of adverse effects; monitor for gepirone-related adverse effects when used with oral lefamulin1. Coadministration of gepirone with other drugs that prolong the QT interval, such as lefamulin may increase the risk of QT interval prolongation and may increase the risk of cardiac arrhythmias. Monitor patients with electrocardiograms more frequently if gepirone is used concomitantly with lefamulin 2.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated metabolism by lefamulin; additive QT interval prolongation

Literature reports

1 report — tap to read

a) 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 Lefamulin and Gepirone together?

Increased gepirone exposure and an increased risk of gepirone-related toxicities, an increased risk of QT interval prolongation and cardiac arrhythmias Always confirm with your pharmacist or prescriber before making any change.

How serious is the Lefamulin and Gepirone 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 Gepirone 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)

  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
  2. Product Information: EXXUA extended-release oral tablets, gepirone extended-release oral tablets. Mission Pharmaceutical Company (per FDA), San Antonio, TX, 2023. DailyMed
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Gepirone

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All Gepirone interactions (77)
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Lefamulin

Keep reading about Lefamulin

All Lefamulin interactions (443) Lefamulin drug information
Also serious with: Lomitapide Ketoconazole Levoketoconazole Ivosidenib
Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Gepirone + Activated Charcoal American Hellebore Arsenic Cesium Ephedra Grapefruit Lithium Sida Cordifolia + 154 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.