Kono Yuki, Niimura Takahiro, Goda Mitsuhiro, Ueta Shiho, Kawada Kei, Miyata Koji, Aizawa Fuka, Yagi Kenta, Izawa-Ishizawa Yuki, Ishizawa Keisuke
Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
Department of Medical Affairs, MSD K.K, Tokyo, Japan.
Cardiovasc Toxicol. 2025 Mar;25(3):498-506. doi: 10.1007/s12012-025-09970-w. Epub 2025 Feb 19.
Macrolides are associated with cardiovascular toxicity risk. However, data on their cardiovascular toxicity profiles beyond QT prolongation are limited, and differences in the profiles among various macrolide antibiotics remain unclear. We investigated the cardiovascular toxicity profiles of different macrolides using VigiBase, a global database of individual case-safety reports. Disproportionality analysis was performed using VigiBase, the WHO Pharmacovigilance database, from 1968 to December 2023. Associations between five macrolides (erythromycin, clarithromycin, azithromycin, josamycin, and roxithromycin) and adverse events (20 cardiovascular toxicities and diarrhea as a positive control) were predicted using the reporting odds ratio. Reported outcomes were evaluated for suggested drug-adverse event associations. Among the 36,129,107 reports analyzed, azithromycin was the most commonly used macrolide, followed by erythromycin, clarithromycin, roxithromycin, and josamycin. Diarrhea was frequently reported among users. Azithromycin use was associated with hypertension, cardiac valve disorders, supraventricular tachyarrhythmias, ventricular tachyarrhythmias, torsade de pointes/QT prolongation, cardiac conduction disorders, heart failure, and hemorrhage-related laboratory abnormalities. Erythromycin and clarithromycin use were also associated with cardiac valve disorders, ventricular tachyarrhythmias, torsade de pointes/QT prolongation, and cardiac conduction disorders. The rates of caused/prolonged hospitalization in azithromycin-related hypertension, heart failure, and bleeding-related laboratory abnormality were 46%, 45%, and 50%, respectively. Each of the macrolide antimicrobials was associated with various cardiovascular toxicities, including Cardiac valve disorder, shock, and QT prolongation. Notably, azithromycin was associated with an increased frequency of reported hypertension and heart failure, distinguishing it from the other drugs. These results highlight the importance of considering the cardiovascular toxicity profile of individual macrolide antibiotics when prescribing them.
大环内酯类药物与心血管毒性风险相关。然而，关于其除QT间期延长之外的心血管毒性特征的数据有限，并且不同大环内酯类抗生素之间的毒性特征差异仍不明确。我们使用VigiBase（一个全球个体病例安全报告数据库）调查了不同大环内酯类药物的心血管毒性特征。使用1968年至2023年12月的WHO药物警戒数据库VigiBase进行了不成比例分析。使用报告比值比预测了五种大环内酯类药物（红霉素、克拉霉素、阿奇霉素、交沙霉素和罗红霉素）与不良事件（20种心血管毒性和腹泻作为阳性对照）之间的关联。对报告的结果进行评估以确定药物与不良事件之间的关联。在分析的36129107份报告中，阿奇霉素是最常用的大环内酯类药物，其次是红霉素、克拉霉素、罗红霉素和交沙霉素。腹泻在使用者中经常被报告。使用阿奇霉素与高血压、心脏瓣膜疾病、室上性快速心律失常、室性快速心律失常、尖端扭转型室速/QT间期延长、心脏传导障碍、心力衰竭以及与出血相关的实验室异常有关。使用红霉素和克拉霉素也与心脏瓣膜疾病、室性快速心律失常、尖端扭转型室速/QT间期延长以及心脏传导障碍有关。阿奇霉素相关的高血压、心力衰竭和与出血相关的实验室异常导致/延长住院的发生率分别为46%、45%和50%。每种大环内酯类抗菌药物都与各种心血管毒性有关，包括心脏瓣膜疾病、休克和QT间期延长。值得注意的是，阿奇霉素与报告的高血压和心力衰竭频率增加有关，这使其与其他药物有所区别。这些结果凸显了在开具大环内酯类抗生素处方时考虑其个体心血管毒性特征的重要性。
