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Published on: November 8, 2015
Impact of Low-Dose Fluconazole on Tacrolimus Dosing in Renal Transplant
Jackie P Johnston1, Elizabeth A Cohen2, Gianna H Casal3
1Department of Pharmacy Practice and Administration, 15484Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Background:
The interaction between azole antifungal therapy and immunosuppressant tacrolimus (TAC) is a barrier to use.
Objective:
This study quantified the drug interaction between low-dose fluconazole (LDF) and TAC to determine the appropriate TAC dose adjustment when used concurrently in renal transplant recipients.
Methods:
We conducted a single-center retrospective chart review of renal transplant patients >18 years who received LDF or nystatin (NYS), and TAC. The primary outcome was the difference in tacrolimus total daily dose (TAC TDD) for LDF versus NYS groups. Secondary outcomes included days with supratherapeutic, therapeutic and subtherapeutic tacrolimus levels, time to therapeutic level, incidence of adverse drug reactions and graft rejection.
Results:
We evaluated 94 patients and included 81. Low-dose fluconazole received a greater TAC TDD prior to post-operative day (POD) 10 (10.5 ± 4.7 mg vs. 7.1 ± 4.5 mg, p < 0.001), but a decreased TAC TDD POD 10 - 30 (8.6 ± 2.2 mg vs. 9.8 ± 0.8 mg, p < 0.001) and following LDF discontinuation (6.9 ± 0.1 mg vs. 9.0 ± 0.4 mg, p < 0.001). Low-dose fluconazole had more patient-days with supratherapeutic (17.9 ± 7.0 vs. 13.9 ± 8.5; p = 0.02) but fewer with subtherapeutic (6.7 ± 5.7 vs. 12.9 ± 7.2; p < 0.01) TAC levels. There was no difference in patient-days with therapeutic TAC levels (15.9 ± 5.8 vs. 14.4 ± 6.6, p = 0.28), meanwhile LDF required less patient-days to therapeutic TAC level (7.1 ± 2.7 vs. 11.5 ± 7.7; p < 0.01). There was no difference in adverse drug reactions between groups and no incidence of graft rejection.
Conclusion:
A 20% reduction in TAC TDD is warranted in renal transplant patients when used concomitantly with LDF to achieve therapeutic levels.
Insights
Concomitant use of low-dose fluconazole (LDF) with tacrolimus (TAC) in renal transplant recipients requires a 20% reduction in TAC total daily dose (TDD) to maintain therapeutic levels. This adjustment ensures optimal immunosuppression and patient outcomes.
Area of Science:
- Pharmacology
- Nephrology
- Transplantation
Background:
- Azole antifungal therapy interactions with immunosuppressants like tacrolimus (TAC) pose challenges in clinical practice.
- Optimizing tacrolimus dosing is crucial for preventing rejection and managing toxicity in transplant recipients.
Purpose of the Study:
- To quantify the drug interaction between low-dose fluconazole (LDF) and tacrolimus (TAC) in renal transplant recipients.
- To determine appropriate TAC dose adjustments when co-administered with LDF.
Main Methods:
- Retrospective chart review of renal transplant patients aged 18 years or older.
- Comparison of tacrolimus total daily dose (TAC TDD) and therapeutic level monitoring between patients receiving LDF and nystatin (NYS).
Main Results:
- Patients receiving LDF had higher initial TAC TDD but decreased TDD post-operatively and after LDF discontinuation compared to NYS.
- LDF use was associated with more supratherapeutic and fewer subtherapeutic TAC levels, with faster achievement of therapeutic levels.
- No significant differences were observed in therapeutic TAC levels, adverse drug reactions, or graft rejection rates between groups.
Conclusions:
- A 20% reduction in TAC TDD is recommended for renal transplant patients concurrently treated with LDF.
- This dose adjustment facilitates achieving and maintaining therapeutic tacrolimus levels, improving safety and efficacy.
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