Huo Ben-Nian, Shu Ling, Xiao Jian-Wen, Yin Nan-Ge, Ai Mao-Lin, Jia Yun-Tao, Song Lin
Department of Pharmacy, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, China.
Department of Pharmacy, People's Hospital of Chongqing Liangjiang New Area, Chongqing, China.
Front Pharmacol. 2024 Sep 30;15:1292163. doi: 10.3389/fphar.2024.1292163. eCollection 2024.
Voriconazole (VRZ) is involved in a variety of drug‒drug interactions (DDIs), but few studies have reported adverse events (AEs) associated with the DDIs of VRZ. The primary goal of this study was to analyse the potential risk factors for AEs caused by DDIs between VRZ and other drugs via the OpenVigil FDA platform and to provide a reference for preventing VRZ DDIs and monitoring clinically related adverse drug events.
A retrospective pharmacovigilance study was conducted to investigate the AEs related to DDIs between VRZ and four categories of drugs: proton pump inhibitors (PPIs), non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressants, and other antibacterial drugs. AE information for the target drugs from the first quarter of 2004 to the third quarter of 2022 was downloaded from the OpenVigil FDA data platform. Four frequency statistical models-the reporting ratio method, Ω shrinkage measure model, combination risk ratio model, and the chi-square statistics model-were used to analyse the AEs related to DDIs and evaluate the correlation and influence of sex and age between the drug(s) and the target AEs detected.
A total of 38 drugs were included, with 262 AEs detected by at least one of the four models and 48 AEs detected by all four models. Some 77 detected AEs were significantly positively correlated with DDIs and were related to higher reporting rates of AEs than when used alone. Graft-versus-host disease was the AE that had the strongest correlation with the drug interaction between VRZ and immunosuppressants (tacrolimus, mycophenolate mofetil, cyclophosphamide, and cyclosporine), and multiple organ dysfunction syndrome was correlated with VRZ in combination with other antibacterial drugs (linezolid, meropenem, cefepime, and vancomycin). Significant sex and age differences in the target AEs were detected for five and nine target drugs, respectively. For VRZ in combination with linezolid, aggravated conditions and respiratory failure should be given more attention in male patients, and mycophenolate mofetil and respiratory failure in female patients. When conditions are aggravated, febrile neutropenia and septic shock should be of particular concern in patients over 18 years of age who use VRZ in combination with ceftazidime, ciprofloxacin, or cytarabine. In patients aged under 18, septic shock should be considered when VRZ is used in combination with meropenem and dexamethasone.
AEs related to DDIs should receive more attention when VRZ is used in combination with PPIs (renal impairment), NSAIDs (constipation and renal failure), immunosuppressants (graft versus host disease, septic shock) and other antibacterial drugs (multiple organ dysfunction syndrome, febrile neutropenia, and respiratory failure). Considering the influence of sex and age differences in VRZ DDIs, these factors need to be considered when assessing the risk of AEs in patients receiving VRZ and other drugs.
伏立康唑（VRZ）涉及多种药物相互作用（DDIs），但很少有研究报道与VRZ药物相互作用相关的不良事件（AEs）。本研究的主要目的是通过OpenVigil FDA平台分析VRZ与其他药物之间药物相互作用导致不良事件的潜在风险因素，并为预防VRZ药物相互作用及监测临床相关药物不良事件提供参考。
进行一项回顾性药物警戒研究，以调查VRZ与四类药物之间药物相互作用相关的不良事件：质子泵抑制剂（PPIs）、非甾体抗炎药（NSAIDs）、免疫抑制剂和其他抗菌药物。从OpenVigil FDA数据平台下载2004年第一季度至2022年第三季度目标药物的不良事件信息。使用四种频率统计模型——报告率法、Ω收缩测量模型、组合风险比模型和卡方统计模型——分析与药物相互作用相关的不良事件，并评估药物与检测到的目标不良事件之间性别和年龄的相关性及影响。
共纳入38种药物，四种模型中至少一种检测到262例不良事件，所有四种模型均检测到48例不良事件。约77例检测到的不良事件与药物相互作用显著正相关，且与单独使用时相比不良事件报告率更高。移植物抗宿主病是与VRZ和免疫抑制剂（他克莫司、霉酚酸酯、环磷酰胺和环孢素）之间药物相互作用相关性最强的不良事件，多器官功能障碍综合征与VRZ联合其他抗菌药物（利奈唑胺、美罗培南、头孢吡肟和万古霉素）相关。分别在五种和九种目标药物中检测到目标不良事件存在显著的性别和年龄差异。对于VRZ联合利奈唑胺，男性患者应更关注病情加重和呼吸衰竭，女性患者应关注霉酚酸酯和呼吸衰竭。当病情加重时，18岁以上使用VRZ联合头孢他啶、环丙沙星或阿糖胞苷的患者应特别关注发热性中性粒细胞减少和感染性休克。18岁以下患者使用VRZ联合美罗培南和地塞米松时应考虑感染性休克。
当VRZ与PPIs（肾功能损害）、NSAIDs（便秘和肾衰竭）、免疫抑制剂（移植物抗宿主病、感染性休克）和其他抗菌药物（多器官功能障碍综合征、发热性中性粒细胞减少和呼吸衰竭）联合使用时，与药物相互作用相关的不良事件应得到更多关注。考虑到VRZ药物相互作用中性别和年龄差异的影响，在评估接受VRZ和其他药物治疗患者的不良事件风险时需要考虑这些因素。
