Drug Interaction Report

Tacrolimus and Lefamulin: Interaction Details

A pharmacist-reviewed analysis of the Tacrolimus and Lefamulin 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

Tacrolimus

Astagraf Astagraf XL® Envarsus Envarsus XR® Prograf Prograf®
+

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
Contraindicated
These should generally not be used together.
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 157 documented Tacrolimus interactions, 2 are rated contraindicated — 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
Contraindicated

What happens

Increased sensitive CYP3A4 substrates exposure and an increased risk of QT interval prolongation

Interaction Deep Dive

Oral lefamulin is contraindicated with sensitive CYP3A4 substrates that prolong the QT interval. Concomitant administration of oral lefamulin with sensitive CYP3A4 substrates may result in increased sensitive CYP3A4 exposure, leading to QT prolongation and cases of torsades de pointes. Concomitant use of lefamulin injection with CYP3A4 substrates does not affect the exposure of CYP3A4 substrates. Mean AUC(0 to inf) and Cmax of midazolam were increased by approximately 200% and 100%, respectively, when oral midazolam (sensitive CYP3A4 substrate) 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 by lefamulin; additive QT interval prolongation

Literature reports

1 report — tap to read

a) Mean AUC(0 to inf) and Cmax of midazolam were increased by approximately 200% and 100%, respectively, when oral midazolam (sensitive CYP3A4 substrate) was administered concomitantly with and at 2 or 4 hours after administration of lefamulin oral tablets 1.

Common questions

Can I take Tacrolimus and Lefamulin together?

Increased sensitive CYP3A4 substrates exposure and an increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.

How serious is the Tacrolimus 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 Tacrolimus 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)

  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
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Tacrolimus

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All Tacrolimus interactions (157) Tacrolimus drug information
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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:

Tacrolimus + Activated Charcoal American Hellebore Arsenic Asarabacca Cesium Ephedra Grapefruit Siberian Cocklebur + 194 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.