Department of Pharmacy Practice and Administration, 15484Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Department of Transplant Surgery, 25047Yale-New Haven Hospital, New Haven, CT, USA.
J Pharm Pract. 2022 Oct;35(5):701-706. doi: 10.1177/08971900211000702. Epub 2021 Mar 24.
The interaction between azole antifungal therapy and immunosuppressant tacrolimus (TAC) is a barrier to use.
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.
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.
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, < 0.001), but a decreased TAC TDD POD 10 - 30 (8.6 ± 2.2 mg vs. 9.8 ± 0.8 mg, < 0.001) and following LDF discontinuation (6.9 ± 0.1 mg vs. 9.0 ± 0.4 mg, < 0.001). Low-dose fluconazole had more patient-days with supratherapeutic (17.9 ± 7.0 vs. 13.9 ± 8.5; = 0.02) but fewer with subtherapeutic (6.7 ± 5.7 vs. 12.9 ± 7.2; < 0.01) TAC levels. There was no difference in patient-days with therapeutic TAC levels (15.9 ± 5.8 vs. 14.4 ± 6.6, = 0.28), meanwhile LDF required less patient-days to therapeutic TAC level (7.1 ± 2.7 vs. 11.5 ± 7.7; < 0.01). There was no difference in adverse drug reactions between groups and no incidence of graft rejection.
A 20% reduction in TAC TDD is warranted in renal transplant patients when used concomitantly with LDF to achieve therapeutic levels.
唑类抗真菌药物治疗与免疫抑制剂他克莫司（TAC）之间的相互作用是一个使用障碍。
本研究量化了低剂量氟康唑（LDF）与 TAC 之间的药物相互作用，以确定在肾移植受者中同时使用时 TAC 剂量调整的适当性。
我们对接受 LDF 或制霉菌素（NYS）和 TAC 的 18 岁以上肾移植患者进行了单中心回顾性图表审查。主要结局是 LDF 组与 NYS 组之间他克莫司总日剂量（TAC TDD）的差异。次要结局包括治疗窗内、治疗窗内和治疗窗外的他克莫司水平天数、达到治疗水平的时间、药物不良反应和移植物排斥的发生率。
我们评估了 94 例患者，其中 81 例接受了低剂量氟康唑。在术后第 10 天（10.5 ± 4.7 mg 比 7.1 ± 4.5 mg， < 0.001）之前，LDF 组接受了更大剂量的 TAC TDD，但在术后第 10-30 天（8.6 ± 2.2 mg 比 9.8 ± 0.8 mg， < 0.001）和 LDF 停药后（6.9 ± 0.1 mg 比 9.0 ± 0.4 mg， < 0.001），TAC TDD 减少。LDF 组有更多的患者日处于超治疗窗（17.9 ± 7.0 比 13.9 ± 8.5； = 0.02），但有更少的患者日处于治疗窗内（6.7 ± 5.7 比 12.9 ± 7.2； < 0.01）。治疗窗内 TAC 水平的患者日无差异（15.9 ± 5.8 比 14.4 ± 6.6， = 0.28），而 LDF 达到治疗窗内 TAC 水平所需的患者日数更少（7.1 ± 2.7 比 11.5 ± 7.7； < 0.01）。两组之间药物不良反应无差异，无移植物排斥发生。
肾移植患者同时使用 LDF 时，TAC TDD 应减少 20%，以达到治疗水平。
