Department of Pharmacy, Cleveland Clinic, Cleveland, Ohio, USA.
Transpl Infect Dis. 2022 Aug;24(4):e13882. doi: 10.1111/tid.13882. Epub 2022 Jun 17.
Clotrimazole troches are used as prophylaxis against oropharyngeal candidiasis post-transplant and have limited systemic absorption. Following several occurrences of tacrolimus concentration fluctuations after clotrimazole discontinuation, its use as prophylaxis was discontinued post-kidney transplant.
We conducted a retrospective cohort study to evaluate the effect of clotrimazole prophylaxis on tacrolimus trough concentrations post-kidney transplant. The study included adult patients who received a kidney transplant at Cleveland Clinic Main Campus from August 1, 2019 to July 1, 2020 and were maintained on per-protocol, standard-dose tacrolimus through 90 days post-transplant. Patients were excluded if they received cyclosporine, systemic antifungals, strong CYP3A4 inhibitors or inducers, or a simultaneous multiorgan transplant. The primary objective was to compare tacrolimus trough concentrations before and after completion of clotrimazole prophylaxis. Secondary objectives were to compare the time to first post-transplant goal tacrolimus trough concentration, the rate of for-cause allograft biopsies within 90 days after transplant, and the incidence and type of candidiasis within 30 days after transplant, pre- and post-protocol change.
Following clotrimazole discontinuation, the median tacrolimus trough concentration decreased from 10.5 ng/ml (IQR 8.4-12.2) to 6.6 ng/ml (IQR 5-8.7, p < 0.0001). No statistically significant differences in the rate of for-cause allograft biopsies (4.9% vs. 9.7%, p = 0.264) or incidence of candidiasis (1.2% vs. 5.4%, p = 0.217) were observed between those who received clotrimazole and those who did not receive clotrimazole.
Our study provides further evidence of a significant drug-drug interaction between tacrolimus and clotrimazole among kidney transplant recipients that can potentially lead to negative allograft outcomes.
克霉唑锭剂用于预防移植后口咽念珠菌病，且全身吸收有限。克霉唑停药后出现几次他克莫司浓度波动后，停止使用克霉唑进行预防。
我们进行了一项回顾性队列研究，以评估克霉唑预防对肾移植后他克莫司谷浓度的影响。该研究纳入 2019 年 8 月 1 日至 2020 年 7 月 1 日在克利夫兰诊所主院区接受肾移植且移植后 90 天内按方案接受标准剂量他克莫司治疗的成年患者。如果患者接受环孢素、全身抗真菌药、强 CYP3A4 抑制剂或诱导剂，或同时接受多器官移植，则将其排除在外。主要目标是比较克霉唑预防完成前后他克莫司谷浓度。次要目标是比较首次移植后目标他克莫司谷浓度的时间、移植后 90 天内因病因进行的同种异体移植物活检率，以及移植后 30 天内念珠菌病的发生率和类型，包括方案前后变化。
克霉唑停药后，他克莫司谷浓度中位数从 10.5ng/ml（IQR 8.4-12.2）降至 6.6ng/ml（IQR 5-8.7，p<0.0001）。接受克霉唑和未接受克霉唑的患者因病因进行的同种异体移植物活检率（4.9%vs.9.7%，p=0.264）或念珠菌病发生率（1.2%vs.5.4%，p=0.217）无统计学显著差异。
我们的研究提供了进一步证据，表明肾移植受者中他克莫司和克霉唑之间存在显著的药物相互作用，可能导致移植物不良结局。
