Metronidazole with Tacrolimus Interaction Details

Brand Names Associated with Metronidazole

Brand Names Associated with Tacrolimus

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Jan 04, 2024

Interaction Effect

Increased risk of QT-interval prolongation and arrhythmia; increased serum tacrolimus concentration and toxicity

Interaction Summary

Case reports showed an association between increased tacrolimus blood concentrations and serum creatinine levels with metronidazole coadministration in renal transplant patients. 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 .

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

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. Case reports showed an association between increased tacrolimus blood concentrations and serum creatinine levels with metronidazole coadministration in renal transplant patients .

Mechanism Of Interaction

Additive QT-interval prolongation; inhibition of CYP3A4-mediated tacrolimus metabolism and p-glycoprotein-mediated tacrolimus excretion by metronidazole

Literature Reports

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 .

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) .

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 .

Metronidazole Overview

• Metronidazole capsules and tablets are used to treat infections of the reproductive system, gastrointestinal (GI) tract, skin, heart, bone, joint, lung, blood, nervous system, and other areas of the body. Metronidazole capsules and tablets are also used to treat sexually transmitted diseases (STDs). Metronidazole extended-release (long-acting) tablets are used to treat bacterial vaginosis (an infection caused by too much of certain types of harmful bacteria in the vagina) in women. Metronidazole is in a class of medications called nitroimidazole antimicrobials. It works by stopping the growth of bacteria.

• Antibiotics will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

Tacrolimus Overview

• Tacrolimus (Astagraf XL, Envarsus XR, Prograf) is used along with other medications to prevent rejection (attack of a transplanted organ by the immune system of a person receiving the organ) in people who have received a kidney transplant. Tacrolimus (Prograf) is also used along with other medications to prevent rejection in people who have received a liver, lung, or heart transplant. Tacrolimus is in a class of medications called immunosupressants. It works by decreasing the activity of the immune system to prevent it from attacking the transplanted organ.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.