Tacrolimus Interaction with Azole Antifungals in Kidney Transplant Recipients: Is Fluconazole or Clotrimazole a Worse Offender?
Jane Revollo1, Vinaya Rao2, Amy Krauss3, Alison L. Apple R. Ph.4, Benjamin Duhart5
1Jane Revello, Pharm.D., CPP, Department of Pharmacy, Atrium Health Carolinas Medical Center, Charlotte, NC, United States of America (USA).
2Vinaya Rao, MD, Department of Nephrology, Medical University of South Carolina, Charleston, SC, United States of America (USA).
3Alison Apple, RPh, MS, Department of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia, PA, United States of America (USA).
4Amy Krauss, PharmD, BCPS, Department of Pharmacy, Gritman Medical Center, Moscow, ID, United States of America (USA).
5Benjamin Duhart, 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).
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 | PP: 12-16 | Volume-4 Issue-1, December 2023 | Retrieval Number: 100.1/ijapsr.F4029103623 | DOI: 10.54105/ijapsr.F4029.124123
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© The Authors. Published by Lattice Science Publication (LSP). This is an open-access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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.
Keywords: Tacrolimus, Fluconazole, Clotrimazole, Kidney transplant
Scope of the Article: Intelligence Applications