Laub Melissa R, Crow Stacy A, Personett Heather A, Dierkhising Ross, Boilson Barry, Razonable Raymund
Division of Pharmacy Services, Mayo Clinic Hospital, Rochester, Minnesota.
Division of Biomedical Statistics and Informatics, Mayo Clinic Hospital, Rochester, Minnesota.
Transpl Infect Dis. 2018 Dec;20(6):e12979. doi: 10.1111/tid.12979. Epub 2018 Sep 3.
Tacrolimus is a cornerstone of immunosuppression after transplantation but is highly susceptible to changes from interacting variables and has a narrow therapeutic index. Clotrimazole troches are commonly used as a non-systemic antifungal to prevent oral candidiasis. Studies suggest that clotrimazole troches, though minimally absorbed systemically, may affect tacrolimus concentrations by inhibition of metabolic enzyme activity in the intestines. However, the magnitude of the impact of clotrimazole on tacrolimus dosing requirements to maintain goal levels is not well described.
To assess this, tacrolimus dose adjustments and trough concentrations were retrospectively examined in 95 heart transplant recipients before and after the discontinuation of clotrimazole.
The median percent tacrolimus dose change was an increase of 66.7% (IQR 28.6%, 100%) after clotrimazole discontinuation, and the median trough concentration percent change from baseline to the first trough after clotrimazole discontinuation (in the absence of a dose change) was -42.5% (IQR -52.3%, -30.9%). Five cases of allograft rejection were observed.
In conclusion, clotrimazole troches exert a meaningful interaction with tacrolimus that requires close monitoring and dose adjustment. The data from this single-center study provide novel information that could guide providers on the degree of tacrolimus dose adjustment needed when discontinuing clotrimazole prophylaxis after heart transplantation.
他克莫司是移植后免疫抑制的基石，但极易受到相互作用变量的影响，且治疗指数较窄。克霉唑含片通常用作非全身性抗真菌药以预防口腔念珠菌病。研究表明，克霉唑含片虽然全身吸收极少，但可能通过抑制肠道中的代谢酶活性来影响他克莫司的浓度。然而，克霉唑对维持目标水平的他克莫司给药需求的影响程度尚未得到充分描述。
为评估这一点，对95名心脏移植受者在停用克霉唑前后的他克莫司剂量调整和谷浓度进行了回顾性研究。
停用克霉唑后，他克莫司剂量变化的中位数百分比增加了66.7%（四分位间距为28.6%，100%），并且从基线到停用克霉唑后的第一个谷浓度（在未改变剂量的情况下）的中位数百分比变化为-42.5%（四分位间距为-52.3%，-30.9%）。观察到5例同种异体移植排斥反应。
总之，克霉唑含片与他克莫司存在显著相互作用，需要密切监测和调整剂量。这项单中心研究的数据提供了新的信息，可指导医疗人员了解心脏移植后停用克霉唑预防用药时他克莫司所需的剂量调整程度。
