Ramos-Ruperez Elena, Escudero-Vilaplana Vicente, Ruiz-Briones Paula, Collado-Borrell Roberto, Villanueva-Bueno Cristina, Revuelta-Herrero José Luis, González-Haba Eva, Garcia-Gonzalez Xandra, Ibañez-Garcia Sara, Perez-Ramirez Sara, Zatarain-Nicolás Eduardo, Herranz Ana, Sanjurjo María
San Pablo Centro de Estudios Universitarios (CEU), University, Madrid, Spain.
Pharmacy Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Front Oncol. 2023 Aug 25;13:1220305. doi: 10.3389/fonc.2023.1220305. eCollection 2023.
The management of cardiotoxicity concerning the use of oral antineoplastic agents (OAAs) is a challenge for healthcare professionals. Our objective was to create a comprehensive medication management guide with dose adjustment recommendations on OAAs concerning cardiotoxic and lipid metabolic adverse events (AEs) to assist healthcare professionals when prescribing OAAs.
A review of the available information on all dose adjustments necessary to safely prescribe and dispense OAAs concerning cardiotoxicity was conducted. In January 2023, we identified all OAAs authorized by the European Medicines Agency (EMA). For each drug, the latest summary of product characteristics (SPC) approved by the EMA and the tertiary data source Lexicomp were reviewed. Cardiotoxic AEs were recorded, namely, QT interval prolongation, decrease in left ventricular ejection fraction (LVEF), imbalances in blood pressure (hypertension and hypotension), alterations in heart rate (tachycardia and bradycardia), and thrombosis. Any available dose adjustment recommendations in case of an occurrence of these adverse events were collected.
In all, 93 different OAAs had been approved by the EMA and were reviewed. Among them, 51.6% have recognized cardiotoxic AEs and 10.8% can cause alterations in lipid metabolism. A total of 27 (29.0%) OAAs had specific recommendations regarding QT prolongation; 88.9% were listed in the SPC and 59.3% in Lexicomp. Eight OAAs (9.68%) have reported a decrease in LVEF, and four of these drugs, namely, encorafenib, lorlatinib, ripretinib, and sunitinib, have specific management recommendations. Almost half (49.5%) of currently approved OAAs can potentially alter blood pressure; 34 (36.6%) of them have been reported to cause hypertension and 12 (12.9%) are related to hypotension. Tachycardia and/or bradycardia are associated with 22.6% and 8.6% of the evaluated drugs, respectively. Regarding thrombosis, 30 (32.3%) of the drugs analyzed included the appearance of a thrombus as a possible AE.
More than half of the OAAs can produce cardiotoxic effects, with the most frequent being blood pressure alteration and QT interval prolongation with a non-depreciable incidence of LV dysfunction or thrombosis. Before starting the treatment, it is necessary to stratify baseline cardiovascular risk, plan a surveillance schedule, and consider referral to cardio-oncology units.
口服抗肿瘤药物（OAA）所致心脏毒性的管理对医疗保健专业人员来说是一项挑战。我们的目标是创建一份全面的药物管理指南，其中包含关于OAA在心脏毒性和脂质代谢不良事件（AE）方面的剂量调整建议，以协助医疗保健专业人员在开具OAA处方时参考。
对安全开具和调配与心脏毒性相关的OAA所需的所有剂量调整的现有信息进行了综述。2023年1月，我们确定了欧洲药品管理局（EMA）批准的所有OAA。对于每种药物，审查了EMA批准的最新产品特性摘要（SPC）和三级数据源Lexicomp。记录心脏毒性AE，即QT间期延长、左心室射血分数（LVEF）降低、血压失衡（高血压和低血压）、心率改变（心动过速和心动过缓）以及血栓形成。收集了这些不良事件发生时的任何可用剂量调整建议。
总共93种不同的OAA已获EMA批准并进行了审查。其中，51.6%有公认的心脏毒性AE，10.8%可导致脂质代谢改变。共有27种（29.0%）OAA对QT延长有具体建议；88.9%列于SPC中，59.3%列于Lexicomp中。8种OAA（9.68%）报告有LVEF降低，其中4种药物，即恩考芬尼、洛拉替尼、瑞派替尼和舒尼替尼，有具体的管理建议。目前批准的OAA中近一半（49.5%）可能会改变血压；其中34种（36.6%）已报告可导致高血压，12种（12.9%）与低血压有关。心动过速和/或心动过缓分别与22.6%和8.6%的评估药物相关。关于血栓形成，所分析的药物中有30种（32.3%）包括血栓出现作为一种可能的AE。
超过一半的OAA可产生心脏毒性作用，最常见的是血压改变和QT间期延长，左心室功能障碍或血栓形成的发生率不可忽视。在开始治疗前，有必要对基线心血管风险进行分层，制定监测计划，并考虑转诊至心脏肿瘤学科室。
