title: Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile.
abstract: BACKGROUND
  Two case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC.
  
  
  METHODS
  In this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose-normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose-normalized TAC levels at baseline and CDI diagnosis.
  
  
  RESULTS
  The 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) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference was found between dose-normalized TAC levels at CDI diagnosis and baseline (P = 0.37).
  
  
  CONCLUSIONS
  CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment.
authors: Department of Pharmacy, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors: C R
authors: CR
authors: Early
authors: Department of Pharmacy, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors: J M
authors: JM
authors: Park
authors: Department of Pharmacy, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors: M P
authors: MP
authors: Dorsch
authors: Department of Pharmacy, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors: K T
authors: KT
authors: Pogue
authors: Department of Pharmacy, University of Michigan Health System, Ann Arbor, Michigan, USA. hanigan@med.umich.edu.
authors: S M
authors: SM
authors: Hanigan
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000066491:Clinical Decision-Making; D016360:Clostridioides difficile / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000188:drug therapy* / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008795:Metronidazole / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D014640:Vancomycin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D008795:Metronidazole; D014640:Vancomycin; D016559:Tacrolimus
keywords: 
  Clostridium difficile
  ; CYP3A4; diarrhea; metronidazole; tacrolimus; trough concentration; vancomycin