Liver injury associated with endothelin receptor antagonists: a pharmacovigilance study based on FDA adverse event reporting system data.

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY International Journal of Clinical Pharmacy Pub Date : 2024-12-01 Epub Date: 2024-06-20 DOI:10.1007/s11096-024-01757-3

Jinjian Gu, Yuting Guo, Bin Wu, Jinhan He

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Abstract

Background: Endothelin receptor antagonists are commonly used in clinical practice, with concerns about their hepatotoxicity.

Aim: This study aimed to conduct a comprehensive pharmacovigilance study based on FDA adverse event reporting system data to evaluate the possible association between endothelin receptor antagonists and drug-induced liver injury.

Method: Adverse event reports from FDA adverse event reporting system between January 2004 and December 2022 were analyzed. Disproportionality algorithms, including reporting odds ratio and information component, were used to evaluate the association between endothelin receptor antagonists and liver injury. Sex- and age-stratified analyses of drug-induced liver injury events were also conducted in relation to endothelin receptor antagonists.

Results: Significant associations between bosentan, macitentan, and liver injury were identified. Bosentan showed a strong link with liver injury, with reporting odds ratios for cholestatic injury at 7.59 (95% confidence interval: 6.90-8.35), hepatocellular injury at 5.63 (5.29-6.00), and serious drug-related hepatic disorders events at 1.33 (1.24-1.43). Drug-induced liver injury signals associated with bosentan were detected in all age groups. Macitentan was associated with liver injury, with reporting odds ratios for hepatic failure at 1.64 (1.39-1.94), cholestatic injury at 1.62 (1.43-1.83), and serious drug-related hepatic disorders events at 1.40 (1.29-1.51). No drug-induced liver injury signal was detected for ambrisentan, and no significant sex differences were observed in drug-induced liver injury events.

Conclusion: Both bosentan and macitentan are associated with liver injury. Routine monitoring of serum aminotransferase levels is recommended, especially in patients at higher risk of liver injury. Further research into drug-drug interactions involving endothelin receptor antagonists is warranted.

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与内皮素受体拮抗剂相关的肝损伤：基于 FDA 不良事件报告系统数据的药物警戒研究。

背景：目的：本研究旨在基于FDA不良事件报告系统数据开展一项全面的药物警戒研究，以评估内皮素受体拮抗剂与药物诱发肝损伤之间可能存在的关联：方法：分析2004年1月至2022年12月期间FDA不良事件报告系统中的不良事件报告。采用包括报告几率比和信息成分在内的比例失调算法来评估内皮素受体拮抗剂与肝损伤之间的关联。还针对内皮素受体拮抗剂对药物引起的肝损伤事件进行了性别和年龄分层分析：结果：发现波生坦、马西坦坦与肝损伤之间存在显著关联。波生坦与肝损伤关系密切，胆汁淤积性肝损伤的报告几率比为 7.59（95% 置信区间：6.90-8.35），肝细胞损伤的报告几率比为 5.63（5.29-6.00），与药物相关的严重肝功能紊乱事件的报告几率比为 1.33（1.24-1.43）。在所有年龄组中都发现了与波生坦相关的药物性肝损伤信号。马西替坦与肝损伤有关，肝衰竭的报告几率比为 1.64（1.39-1.94），胆汁淤积性肝损伤为 1.62（1.43-1.83），严重药物相关肝功能紊乱事件为 1.40（1.29-1.51）。安立生坦未发现药物性肝损伤信号，在药物性肝损伤事件中也未观察到明显的性别差异：结论：波生坦和马基坦都与肝损伤有关。建议对血清转氨酶水平进行常规监测，尤其是对肝损伤风险较高的患者。有必要进一步研究内皮素受体拮抗剂的药物相互作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Clinical Pharmacy PHARMACOLOGY & PHARMACY-

CiteScore

4.10

自引率

8.30%

发文量

131

审稿时长

4-8 weeks

期刊介绍： The International Journal of Clinical Pharmacy (IJCP) offers a platform for articles on research in Clinical Pharmacy, Pharmaceutical Care and related practice-oriented subjects in the pharmaceutical sciences. IJCP is a bi-monthly, international, peer-reviewed journal that publishes original research data, new ideas and discussions on pharmacotherapy and outcome research, clinical pharmacy, pharmacoepidemiology, pharmacoeconomics, the clinical use of medicines, medical devices and laboratory tests, information on medicines and medical devices information, pharmacy services research, medication management, other clinical aspects of pharmacy. IJCP publishes original Research articles, Review articles , Short research reports, Commentaries, book reviews, and Letters to the Editor. International Journal of Clinical Pharmacy is affiliated with the European Society of Clinical Pharmacy (ESCP). ESCP promotes practice and research in Clinical Pharmacy, especially in Europe. The general aim of the society is to advance education, practice and research in Clinical Pharmacy . Until 2010 the journal was called Pharmacy World & Science.