Zhang Jiali, Ma Danyi, Chen Meng, Hu Yanting, Chen Xveying, Chen Jingyu, Huang Man, Dai Haibin
Department of Pharmacy, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of General Intensive Care Unit, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Pharmacol. 2024 Feb 6;15:1308260. doi: 10.3389/fphar.2024.1308260. eCollection 2024.
Drug-drug interactions (DDIs) are a major but preventable cause of adverse drug reactions. There is insufficient information regarding DDIs in lung transplant recipients. This study aimed to determine the prevalence of potential DDIs (pDDIs) in intensive care unit (ICU) lung transplant recipients, identify the real DDIs and the most frequently implicated medications in this vulnerable population, and determine the risk factors associated with pDDIs. This retrospective cross-sectional study included lung transplant recipients from January 2018 to December 2021. Pertinent information was retrieved from medical records. All prescribed medications were screened for pDDIs using the Lexicomp drug interaction software. According to this interaction software, pDDIs were classified as C, D, or X (C = monitor therapy, D = consider therapy modification, X = avoid combination). The Drug Interaction Probability Scale was used to determine the causation of DDIs. All statistical analysis was performed in SPSS version 26.0. 114 patients were qualified for pDDI analysis, and total pDDIs were 4051. The most common type of pDDIs was category C (3323; 82.0%), followed by D (653; 16.1%) and X (75; 1.9%). Voriconazole and posaconazole were the antifungal medicine with the most genuine DDIs. Mean tacrolimus concentration/dose (Tac C/D) before or after co-therapy was considerably lower than the Tac C/D during voriconazole or posaconazole co-therapy ( < 0.001, = 0.027). Real DDIs caused adverse drug events (ADEs) in 20 patients. Multivariable logistic regression analyses found the number of drugs per patient (OR, 1.095; 95% CI, 1.048-1.145; < 0.001) and the Acute Physiology and Chronic Health Evaluation II (APACHE Ⅱ) score (OR, 1.097; 95% CI, 1.021-1.179; = 0.012) as independent risk factors predicting category X pDDIs. This study revealed a high incidence of both potential and real DDIs in ICU lung transplant recipients. Immunosuppressive drugs administered with azole had a high risk of causing clinically significant interactions. The number of co-administered drugs and APACHE Ⅱ score were associated with an increased risk of category × drug interactions. Close monitoring of clinical and laboratory parameters is essential for ensuring successful lung transplantation and preventing adverse drug events associated with DDIs.
药物相互作用（DDIs）是药物不良反应的一个主要但可预防的原因。关于肺移植受者药物相互作用的信息不足。本研究旨在确定重症监护病房（ICU）肺移植受者中潜在药物相互作用（pDDIs）的发生率，识别该脆弱人群中真正的药物相互作用及最常涉及的药物，并确定与pDDIs相关的危险因素。这项回顾性横断面研究纳入了2018年1月至2021年12月的肺移植受者。从医疗记录中检索相关信息。使用Lexicomp药物相互作用软件对所有处方药物进行pDDIs筛查。根据该相互作用软件，pDDIs被分类为C、D或X（C = 监测治疗，D = 考虑调整治疗，X = 避免联合使用）。使用药物相互作用概率量表来确定药物相互作用的因果关系。所有统计分析均在SPSS 26.0版中进行。114例患者符合pDDI分析条件，pDDIs总数为4051例。最常见的pDDIs类型为C类（3323例；82.0%），其次是D类（653例；16.1%）和X类（75例；1.9%）。伏立康唑和泊沙康唑是真正药物相互作用最多的抗真菌药物。联合治疗前后的平均他克莫司浓度/剂量（Tac C/D）显著低于伏立康唑或泊沙康唑联合治疗期间的Tac C/D（<0.001， = 0.027）。真正的药物相互作用在20例患者中导致了药物不良事件（ADEs）。多变量逻辑回归分析发现，每位患者的药物数量（OR，1.095；95%CI，1.048 - 1.145；<0.001）和急性生理与慢性健康状况评分II（APACHEⅡ）（OR，1.097；95%CI，1.021 - 1.179； = 0.012）是预测X类pDDIs的独立危险因素。本研究揭示了ICU肺移植受者中潜在和真正药物相互作用的高发生率。与唑类药物联合使用的免疫抑制药物有很高的风险导致具有临床意义的相互作用。联合使用药物的数量和APACHEⅡ评分与X类药物相互作用风险增加相关。密切监测临床和实验室参数对于确保肺移植成功及预防与药物相互作用相关的药物不良事件至关重要。
