El-Sayed Anas, Vidal Jennifer, Khanmoradi Kamran, Knorr John P
Department of Pharmacy, Einstein Medical Center Philadelphia, Philadelphia, Pennsylvania.
Department of Transplant Surgery, Einstein Medical Center Philadelphia, Philadelphia, Pennsylvania.
Transplant Proc. 2021 Jun;53(5):1583-1588. doi: 10.1016/j.transproceed.2021.03.032. Epub 2021 May 4.
Tacrolimus, an immunosuppressant prescribed to reduce the risk of organ rejection, is metabolized by cytochrome P450 and is a substrate for P-glycoprotein. Many medications affect tacrolimus concentrations, making it difficult to maintain exposure within its narrow therapeutic index. Clotrimazole troches, prescribed to posttransplant recipients immediately for the first 30 days for oral candidiasis prevention, are considered nonsystemic. However, data suggest a potential drug interaction, affecting tacrolimus exposure. To assess the magnitude of the effect of clotrimazole on tacrolimus trough levels, 97 kidney transplant recipients, on a stable dose of tacrolimus, were retrospectively evaluated. Tacrolimus trough concentrations were analyzed 7 and 14 days before and after discontinuation of clotrimazole. The median change in tacrolimus trough level was -1.3 ng/mL (confidence interval, -2.5, -1.0; P < .001) at day 7 and -2.8 ng/mL (confidence interval, -3.3, -1.6; P < .001) at day 14 after clotrimazole discontinuation, from a median baseline of 8.9 ng/mL. Overall, a reduction in tacrolimus level was observed in 60% of patients after discontinuation of clotrimazole. When assessing the effect of race and sex, no influence was found on the degree of change in tacrolimus level after clotrimazole discontinuation. In conclusion, clotrimazole exerts a significant interaction on tacrolimus where close monitoring of tacrolimus trough levels after discontinuation of clotrimazole is warranted.
他克莫司是一种用于降低器官排斥风险的免疫抑制剂，通过细胞色素P450代谢，是P-糖蛋白的底物。许多药物会影响他克莫司的浓度，使其难以在狭窄的治疗指数范围内维持有效血药浓度。克霉唑含片在移植后最初30天内立即开给受者用于预防口腔念珠菌病，被认为是局部用药。然而，数据表明可能存在药物相互作用，影响他克莫司的血药浓度。为评估克霉唑对他克莫司谷浓度的影响程度，对97名接受稳定剂量他克莫司治疗的肾移植受者进行了回顾性评估。在停用克霉唑前后7天和14天分析他克莫司谷浓度。克霉唑停用后第7天，他克莫司谷浓度的中位数变化为-1.3 ng/mL（置信区间为-2.5，-1.0；P < 0.001），第14天为-2.8 ng/mL（置信区间为-3.3，-1.6；P < 0.001），基线中位数为8.9 ng/mL。总体而言，60%的患者在停用克霉唑后他克莫司水平降低。在评估种族和性别的影响时，未发现对停用克霉唑后他克莫司水平变化程度有影响。总之，克霉唑对他克莫司有显著的相互作用，停用克霉唑后有必要密切监测他克莫司谷浓度。
