Metronidazole and Tacrolimus: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Tacrolimus
Metronidazole
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 risk of QT-interval prolongation and arrhythmia; increased serum tacrolimus concentration and toxicity
Interaction Deep Dive
Case reports showed an association between increased tacrolimus blood concentrations and serum creatinine levels with metronidazole coadministration in renal transplant patients23. Concurrent use of metronidazole with tacrolimus was a probable cause of 9 episodes of QT-interval prolongation in a study of cardiac ICU patients. Use caution with coadministration of metronidazole with tacrolimus and other QT-interval prolonging drugs, as life-threatening additive effects on the QT interval, including torsades de pointes, may occur. Consider close ECG monitoring at baseline and during concurrent therapy with QT-interval prolonging drugs 1.
Why it happens (mechanism)
Additive QT-interval prolongation; inhibition of CYP3A4-mediated tacrolimus metabolism and p-glycoprotein-mediated tacrolimus excretion by metronidazole
Literature reports
3 reports — tap to read
a) In a retrospective study, 164 of 501 patients admitted in cardiac ICUs (87.7%) developed QT-interval prolongation potentially linked to inhibition of CYP450-mediated metabolism. Out of 1027 potential interactions, 9 interactions occurred with concurrent metronidazole and tacrolimus treatment. No patients developed torsades de pointes during their ICU stays. Close ECG monitoring at baseline and during concurrent therapy with drugs known to cause QT-interval prolongation is recommended 1.
b) Renal toxicity occurred with concomitant administration of metronidazole with tacrolimus 8 mg/day and prednisone 20 mg/day in a 24-year-old man treated with immunosuppressant therapy following renal transplant. During the first 3 months post-transplant, the patient's serum creatinine ranged between 1.6 and 1.8 mg/dL (140 and 160 mcmol/L), with tacrolimus plasma trough concentrations ranging between 7 and 10 nanogram/mL (ng/mL; 8.7 and 12 nanomol/L). A 14-day regimen of metronidazole 200 mg/day for Clostridium difficile infection led to increased tacrolimus plasma trough concentrations (ie, 26.3 ng/mL or 32.7 nanomol/L) and a rise in serum creatinine to 3.3 mg/dL (292 mcmol/L). The next dose of tacrolimus was withheld, followed by a tacrolimus dose reduction. Tacrolimus trough concentrations declined to 9.4 ng/mL (11.7 nanomol/L) 2 days after metronidazole discontinuation. After upward dose titration, the tacrolimus trough plasma concentration stabilized between 6.0 and 7.8 ng/mL (7.5 and 9.7 nanomol/L) and serum creatinine ranged between 1.7 and 1.9 mg/dL (150 and 168 mcmol/L) 2.
c) Tacrolimus blood concentrations and serum creatinine levels increased with metronidazole coadministration in 69-year-old renal transplant recipient with a plasma creatinine of 0.15 mmol/L stabilized on tacrolimus 5 mg daily (mean trough tacrolimus level, 9.0 mcg/L or 0.011 mcmol/L). During a 14-day regimen of metronidazole 1200 mg/day for Clostridium difficile, his tacrolimus plasma concentration increased to 17.9 mcg/L (0.0223 mcmol/L) and plasma creatinine increased to 0.21 mmol/L. His tacrolimus plasma concentration and plasma creatinine fell to 8.1 mcg/L (0.0101 mcmol/L) and 0.16 mmol/L, respectively, following a tacrolimus dose reduction to 2 mg/day and decreased to 5.2 mcg/L (0.0065 mcmol/L) after metronidazole discontinuation. With upward dose titration, tacrolimus levels increased to 8.8 mcg/L (0.0109 mcmol/L) and remained stable 3.
Common questions
Can I take Metronidazole and Tacrolimus together?
Increased risk of QT-interval prolongation and arrhythmia; increased serum tacrolimus concentration and toxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Metronidazole and Tacrolimus interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Metronidazole or Tacrolimus 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 (3)
- Armahizer MJ, Seybert AL, Smithburger PL, et al: Drug-drug interactions contributing to QT prolongation in cardiac intensive care units. J Crit Care 2013; 28(3):243-249. PubMed
- Page RL II, Klem PM, & Rogers C: Potential elevation of tacrolimus trough concentrations with concomitant metronidazole therapy. Ann Pharmacother 2005; 39:1109-1113. PubMed
- Herzig K & Johnson DW: Marked elevation fo blood cyclosporin and tacrolimus levels due to concurrent metronidazole therapy (letter). Nephrol Dial Transplant 1999; 15:521-523.
Keep reading about Tacrolimus
Keep reading about Metronidazole
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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