Potential elevation of tacrolimus trough concentrations with concomitant metronidazole therapy.
OBJECTIVE
To report the occurrence of a potential tacrolimus elevation in a renal transplant recipient after adding metronidazole to the medication regimen.


METHODS
A 24-year-old white man status post living-related renal transplant who had been stabilized on tacrolimus 4 mg twice daily (trough concentrations 7-10 ng/mL) for 2 months and prednisone 20 mg daily presented to the clinic with severe diarrhea. Stool cultures were positive for Clostridium difficile, and therapy with metronidazole 500 mg 4 times daily was initiated. Between days 4 and 14 of metronidazole therapy, the patient's tacrolimus trough concentration and serum creatinine level increased to maximum levels of 26.3 ng/mL and 3.3 mg/dL (baseline 1.6-1.8 mg/dL), respectively. Tacrolimus was withheld for one dose and then decreased to 1 mg twice daily. Two days after metronidazole discontinuation, tacrolimus trough concentrations dropped to 9.4 ng/mL and serum creatinine to 2.3 mg/dL, warranting a tacrolimus dose increase to 3 mg daily.


CONCLUSIONS
As of April 15, 2005, one other case has been reported documenting an elevation in tacrolimus concentrations with the addition of metronidazole. The possible mechanism may be related to metronidazole's weak inhibition of CYP3A4 and, possibly, P-glycoprotein. According to the Naranjo probability scale, metronidazole was the probable cause of this adverse reaction.


CONCLUSIONS
Coadministration of tacrolimus with metronidazole may result in elevated tacrolimus concentrations, possibly leading to tacrolimus toxicity. Practitioners should be aware of this potential interaction and closely monitor tacrolimus concentrations and renal function.
Page
Robert Lee
RL
Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80262-0001, USA. robert.page@uchsc.edu
Klem
Patrick M
PM
Rogers
Christin
C
D000328:Adult; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy*; D016030:Kidney Transplantation / Q000379:methods; D008297:Male; D008795:Metronidazole / Q000097:blood / Q000627:therapeutic use*; D016559:Tacrolimus / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome
D008795:Metronidazole; D003404:Creatinine; D016559:Tacrolimus