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Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile

C R Early1, J M Park1, M P Dorsch1

  • 1Department of Pharmacy, University of Michigan Health System, Ann Arbor, Michigan, USA.

Transplant Infectious Disease : an Official Journal of the Transplantation Society
|August 9, 2016
PubMed
Abstract

Insights

Metronidazole treatment for Clostridium difficile infection (CDI) did not significantly increase tacrolimus (TAC) levels compared to vancomycin. Transplant patients on TAC require dose adjustments for CDI, regardless of the antibiotic used.

Area of Science:

  • Pharmacology
  • Transplant Medicine
  • Infectious Diseases

Background:

  • Case reports suggest metronidazole may increase tacrolimus (TAC) levels during Clostridium difficile infection (CDI) treatment.
  • Limited literature exists on the pharmacokinetic interaction between metronidazole and TAC.
  • Clinical significance of this potential drug interaction in transplant patients is unclear.

Purpose of the Study:

  • To determine the clinical significance of metronidazole's potential interaction with tacrolimus (TAC) in transplant patients undergoing treatment for Clostridium difficile infection (CDI).
  • To quantify the magnitude of pharmacokinetic interaction between metronidazole and TAC.

Main Methods:

  • Retrospective study of 52 adult solid organ transplant patients.
  • Investigated the effects of CDI and metronidazole treatment on TAC levels.
  • Primary outcome: difference in dose-normalized TAC levels from baseline to symptom resolution between metronidazole and vancomycin treatment groups.

Main Results:

  • Average change in log-transformed dose-normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n=35) and 1.04 for vancomycin (n=17).
  • Mean difference between groups was 0.96 (95% CI: 0.74-1.24), indicating no significant difference.
  • No significant difference in dose-normalized TAC levels at CDI diagnosis compared to baseline (P=0.37).

Conclusions:

  • Metronidazole treatment for CDI was not associated with a >30% increase in TAC levels compared to vancomycin.
  • Both metronidazole and vancomycin groups required TAC dose adjustments to maintain therapeutic levels.
  • Metronidazole-treated patients did not require significantly greater TAC dose adjustments than vancomycin-treated patients.
Keywords:
Clostridium difficileCYP3A4diarrheametronidazoletacrolimustrough concentrationvancomycin

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