Drug Interaction Between Metronidazole and Tacrolimus
Metronidazole can be taken with this medication regimen, but tacrolimus levels must be monitored closely as metronidazole significantly increases tacrolimus concentrations, potentially causing nephrotoxicity. 1, 2
Critical Drug Interaction: Tacrolimus and Metronidazole
Mechanism and Clinical Significance
Metronidazole inhibits CYP3A4 and possibly P-glycoprotein, leading to elevated tacrolimus concentrations that can result in nephrotoxicity 1
Tacrolimus trough concentrations can increase by 52-65% when metronidazole is administered at 1000 mg/day, with the magnitude depending on metronidazole dose and route of administration 2
Case reports document tacrolimus levels rising from 7-10 ng/mL to 26.3 ng/mL within 4-14 days of starting metronidazole 500 mg four times daily, accompanied by serum creatinine elevation from 1.6-1.8 mg/dL to 3.3 mg/dL 1
Management Protocol
Before starting metronidazole:
- Obtain baseline tacrolimus trough level and serum creatinine 1
During metronidazole therapy (500 mg three times daily):
- Monitor tacrolimus trough concentrations every 3-4 days during the first two weeks of concomitant therapy 1, 2
- Monitor renal function (serum creatinine) concurrently 1
- Be prepared to reduce tacrolimus dose by 50-75% if trough levels exceed therapeutic range 1
- Consider withholding one tacrolimus dose if levels become significantly elevated 1
After metronidazole discontinuation:
- Check tacrolimus levels 2 days after stopping metronidazole, as concentrations will drop rapidly 1
- The interaction may persist for up to one month after metronidazole cessation 2
- Anticipate need to increase tacrolimus dose back toward baseline 1
Other Drug Interactions in This Regimen
Esomeprazole Considerations
- No clinically significant interaction exists between esomeprazole and tacrolimus requiring dose adjustment
Mycophenolate Mofetil Interactions
- Mycophenolate mofetil does not affect tacrolimus clearance when co-administered 3
- No interaction between metronidazole and mycophenolate mofetil has been documented
- No interaction between metronidazole and esomeprazole requires dose adjustment
Metronidazole Dosing Verification
The proposed regimen of metronidazole 500 mg three times daily is appropriate for treating C. difficile infection or anaerobic bacterial infections 4, 5
- Standard dosing for bacterial vaginosis and other infections is metronidazole 500 mg orally twice daily for 7 days 4
- For C. difficile infection, metronidazole 500 mg three times daily for 10 days is an acceptable alternative when vancomycin or fidaxomicin is unavailable 5
Common Pitfalls to Avoid
- Do not assume tacrolimus levels will remain stable during metronidazole therapy—this is a clinically significant interaction requiring proactive monitoring 1, 2
- Do not wait for symptoms of tacrolimus toxicity (tremor, nephrotoxicity, neurotoxicity) before checking levels 1
- Do not forget to re-escalate tacrolimus dose after metronidazole is discontinued, as levels will drop 1
- Advise the patient to avoid alcohol during metronidazole treatment and for 24 hours after completion 4