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Published December 30, 2023 | Version CC BY-NC-ND 4.0
Journal article Open

Tacrolimus Interaction with Azole Antifungals in Kidney Transplant Recipients: Is Fluconazole or Clotrimazole a Worse Offender?

  • 1. Jr., MS, PharmD, Department of Clinical Pharmacy and Translational Research, University of Tennessee Health Science Center College of Pharmacy, Memphis, TN, United States of America (USA).
  • 1. Pharm.D., CPP, Department of Pharmacy, Atrium Health Carolinas Medical Center, Charlotte, NC, United States of America (USA).
  • 2. MD, Department of Nephrology, Medical University of South Carolina, Charleston, SC, United States of America (USA).
  • 3. RPh, MS, Department of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia, PA, United States of America (USA).
  • 4. PharmD, BCPS, Department of Pharmacy, Gritman Medical Center, Moscow, ID, United States of America (USA).
  • 5. Jr., MS, PharmD, Department of Clinical Pharmacy and Translational Research, University of Tennessee Health Science Center College of Pharmacy, Memphis, TN, United States of America (USA).

Description

Abstract: The utilization of rabbit ant thymocyte globulin induction with tacrolimus-based maintenance immunosuppression may increase the risk for opportunistic fungal infections, particularly oral-esophageal candidiasis. Both are commonly prescribed for deceased donor kidney transplant recipients Tacrolimus (TAC), a calcineurin inhibitor, is metabolized hepatically by cytochrome P450 3A4/5 enzymes. Due to this, a drug interaction can occur with TAC and either fluconazole (FCZ) or clotrimazole (CTMZ). Both are commonly used for antifungal prophylaxis. While both FCZ and CTMZ inhibit CYP3A4/5, systemic absorption of CTMZ is minimal, theoretically limiting the interaction with TAC and reducing the need for dose readjustments. Medical records for adult patients receiving a renal transplant between March 2009 and September 2011 were retrospectively reviewed for TAC dose adjustments following discontinuation of the antifungal agent required to maintain therapeutic TAC blood levels. The change in TAC dose: trough ratio 4-8 weeks after azole discontinuation was greater in patients receiving FCZ compared to CTMZ (FCZ +92.9% vs CTMZ +43.4%, p=0.004). In addition, the proportion of patients requiring ≥30% TAC dose increase was 70% with FCZ versus 45% with CTMZ (p=0.006). The choice of antifungal also did not affect the number of sub-therapeutic TAC levels, the number of patients with sub-therapeutic levels pre- or post-discontinuation, or incidence of biopsy-proven allograft rejection.

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Additional details

Identifiers

DOI
10.54105/ijapsr.F4029.124123
EISSN
2582-7618

Dates

Accepted
2023-12-15
Manuscript received on 05 September 2023 | Revised Manuscript received on 08 November 2023 | Manuscript Accepted on 15 December 2023 | Manuscript published on 30 December 2023

References

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