Drug Interaction Report

Tacrolimus and Fentanyl Transdermal Patch: Interaction Details

A pharmacist-reviewed analysis of the Tacrolimus and Fentanyl Transdermal Patch 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®
+

Fentanyl Transdermal Patch

Duragesic®
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 157 documented Tacrolimus interactions, 150 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
probable
Severity
Major

What happens

Decreased tacrolimus clearance

Interaction Deep Dive

Concurrent use of a fentanyl and tacrolimus (both narrow therapeutic index CYP3A4 substrates) decreased the clearance of tacrolimus, which may lead to increased blood concentrations and toxicity of tacrolimus. Concomitant use decreased the clearance of tacrolimus 1.9-fold in a small retrospective study. If used concurrently, consider a 40% dose reduction of tacrolimus1.

Why it happens (mechanism)

CYP3A4-mediated tacrolimus metabolism

Literature reports

1 report — tap to read

a) The clearance of tacrolimus decreased 1.9-fold with concomitant use of fentanyl (from 1.28 to 0.68 mL/min/kg) in a small retrospective study of patients with allogeneic hematopoietic stem cell transplantation (N=8). After stopping fentanyl, the clearance of tacrolimus went back to 82.8% of the original tacrolimus clearance prior to administration. Patients received tacrolimus 0.02 mg/kg/day over 24 hours continuous IV infusion the day prior to transplantation with simultaneous fentanyl 6.25 or 12.5 mcg/kg/hour with rescue fentanyl IV for 1 hour for breakthrough pain. Based upon Horn's drug interaction probability scores of 3 to 5 in all patients, the probability of a drug interaction between fentanyl and tacrolimus was deemed possible (n=5) or probable (n=1) 1.

Common questions

Can I take Tacrolimus and Fentanyl Transdermal Patch together?

Decreased tacrolimus clearance Always confirm with your pharmacist or prescriber before making any change.

How serious is the Tacrolimus and Fentanyl Transdermal Patch 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 "probable". Good supporting evidence, though not definitively proven.

Questions for your pharmacist

  • Does my dose of Tacrolimus or Fentanyl Transdermal Patch 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. Kitazawa F, Fuchida SI, Kado Y, et al: Pharmacokinetic interaction between tacrolimus and fentanyl in patients receiving allogeneic hematopoietic stem cell transplantation. Ann Transplant 2017; 22:575-580. PubMed
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Fentanyl Transdermal Patch

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All Fentanyl Transdermal Patch interactions (493) Fentanyl Transdermal Patch drug information
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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.