Unexpected Clinically Significant Drug-Drug Interaction between Tacrolimus and Metronidazole in the Early Period after Renal Transplantation: A Literature Review.

Abstract

Introduction: Drug interactions necessitate careful consideration in clinical practice. It is imperative for clinicians and pharmacists to monitor drug exposure and the co-administration of medications promptly in order to avert adverse outcomes and achieve optimal efficacy.

Objectives: The prevalence of oral lesions varies from 28% to 60% in the short term after renal transplantation. The clinical use of metronidazole in the treatment of anaerobic bacterial infections among solid organ transplant recipients has been complicated by the potentially significant and unpredictable drug-drug interactions.

Methods: We present an unexpected, clinically significant drug-drug interaction between tacrolimus and metronidazole in the early period after renal transplantation and describe the potential mechanism and clinical characteristics of this drug-drug interaction through a literature review.

Results: A 34-year-old female experienced a 65% increase in dose-normalized tacrolimus trough concentration after intravenous administration of metronidazole at 1000 mg/day for 8 days. When metronidazole was switched from intravenous to oral for 5 days, dose-normalized tacrolimus trough concentration was still increased by 52.4%. The magnitude of tacrolimus-metronidazole drug-drug interaction seems to be contingent upon the dose of metronidazole and the route of metronidazole administration. After cessation of metronidazole for one month, this drug-drug interaction, as assessed by weight-normalized tacrolimus dose, may still persist.

Conclusion: In the early period following renal transplantation, the long-term concomitant use of metronidazole is likely to elevate the trough concentration of tacrolimus. Gene screening for CYP3A5*3/*3 and ABCB1 3435C>T in recipients of solid organ transplants may support individualized tacrolimus prescribing and facilitate the mitigation of risks associated with drug-drug interactions.