Drug-induced liver injury associated with pretomanid, bedaquiline, and linezolid: Insights from FAERS database analysis

IF 3.1 3区医学 Q2 PHARMACOLOGY & PHARMACY

British journal of clinical pharmacology Pub Date : 2024-10-17 DOI:10.1111/bcp.16318

Qingfeng He, Yang Li, Sifan Liu, Hao Xue, Xiaoqiang Xiang, Tao Wang, Zhen Feng

{"title":"Drug-induced liver injury associated with pretomanid, bedaquiline, and linezolid: Insights from FAERS database analysis","authors":"Qingfeng He, Yang Li, Sifan Liu, Hao Xue, Xiaoqiang Xiang, Tao Wang, Zhen Feng","doi":"10.1111/bcp.16318","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aims</h3>\n \n <p>The emergence of drug-resistant tuberculosis has necessitated novel treatments like the pretomanid, bedaquiline and linezolid (BPaL) regimen. This study investigated the association of drug-induced liver injury (DILI) with the BPaL regimen compared to first-line antituberculosis drugs (isoniazid, rifampin, pyrazinamide and ethambutol [HRZE]).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>A retrospective pharmacovigilance analysis was conducted using data from the US Food and Drug Administration Adverse Event Reporting System database from July 2019 to June 2023. Disproportionality analysis was employed to calculate the reporting odds ratio (ROR) of DILI for each component of the BPaL regimen. Onset time and mortality rates of DILI across different regimens were also compared.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>We identified 1242 cases of BPaL-related DILI. Most cases occurred in individuals under 65 years of age (63.8%), with more male patients affected than females (51.4% <i>vs</i> 39.5%). The association between antituberculosis drugs and DILI was stronger for the HRZE regimen (ROR = 7.99, 95% confidence interval [CI] 7.74-8.25) than the BPaL regimen (ROR = 4.75, 95% CI 4.55-4.97). The median onset time for DILI was significantly shorter with the BPaL regimen (8 days, interquartile range [IQR] 3-28) compared to the HRZE regimen (20 days, IQR 6-48) (<i>P</i> < .001). Additionally, the BPaL regimen was associated with a higher risk of death due to DILI compared to the HRZE regimen (14.1% <i>vs</i> 10.4%, <i>P</i> = .003).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Although the BPaL regimen had a lower overall risk of DILI compared to the HRZE regimen, it was significantly associated with DILI, indicating a need for careful monitoring during treatment.</p>\n </section>\n </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"799-807"},"PeriodicalIF":3.1000,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"British journal of clinical pharmacology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/bcp.16318","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Aims

The emergence of drug-resistant tuberculosis has necessitated novel treatments like the pretomanid, bedaquiline and linezolid (BPaL) regimen. This study investigated the association of drug-induced liver injury (DILI) with the BPaL regimen compared to first-line antituberculosis drugs (isoniazid, rifampin, pyrazinamide and ethambutol [HRZE]).

Methods

A retrospective pharmacovigilance analysis was conducted using data from the US Food and Drug Administration Adverse Event Reporting System database from July 2019 to June 2023. Disproportionality analysis was employed to calculate the reporting odds ratio (ROR) of DILI for each component of the BPaL regimen. Onset time and mortality rates of DILI across different regimens were also compared.

Results

We identified 1242 cases of BPaL-related DILI. Most cases occurred in individuals under 65 years of age (63.8%), with more male patients affected than females (51.4% vs 39.5%). The association between antituberculosis drugs and DILI was stronger for the HRZE regimen (ROR = 7.99, 95% confidence interval [CI] 7.74-8.25) than the BPaL regimen (ROR = 4.75, 95% CI 4.55-4.97). The median onset time for DILI was significantly shorter with the BPaL regimen (8 days, interquartile range [IQR] 3-28) compared to the HRZE regimen (20 days, IQR 6-48) (P < .001). Additionally, the BPaL regimen was associated with a higher risk of death due to DILI compared to the HRZE regimen (14.1% vs 10.4%, P = .003).

Conclusions

Although the BPaL regimen had a lower overall risk of DILI compared to the HRZE regimen, it was significantly associated with DILI, indicating a need for careful monitoring during treatment.

查看原文本刊更多论文

与普托莫尼、贝达喹啉和利奈唑胺相关的药物诱发肝损伤：FAERS 数据库分析的启示。

目的：随着耐药性结核病的出现，有必要采用新的治疗方法，如前马尼、贝达喹啉和利奈唑胺（BPaL）治疗方案。本研究调查了与一线抗结核药物（异烟肼、利福平、吡嗪酰胺和乙胺丁醇[HRZE]）相比，BPaL方案与药物性肝损伤（DILI）的相关性：利用美国食品和药物管理局不良事件报告系统数据库中2019年7月至2023年6月的数据进行了一项回顾性药物警戒分析。采用比例失调分析法计算 BPaL 方案各组成部分的 DILI 报告几率（ROR）。此外，还比较了不同方案中 DILI 的发病时间和死亡率：结果：我们发现了 1242 例与 BPaL 相关的 DILI 病例。大多数病例发生在 65 岁以下的人群中（63.8%），男性患者多于女性（51.4% 对 39.5%）。与BPaL方案（ROR = 4.75，95% 置信区间 [CI] 4.55-4.97）相比，HRZE方案（ROR = 7.99，95% 置信区间 [CI] 7.74-8.25）的抗结核药物与DILI之间的关联性更强。与HRZE方案（20天，IQR 6-48）相比，BPaL方案的DILI中位发病时间（8天，四分位数间距[IQR] 3-28）明显更短（P 结论：BPaL方案的DILI中位发病时间比HRZE方案更短（P 结论：BPaL方案的DILI中位发病时间比HRZE方案更短）：虽然与HRZE方案相比，BPaL方案发生DILI的总体风险较低，但它与DILI显著相关，表明在治疗期间需要仔细监测。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

British journal of clinical pharmacology 医学-药学

CiteScore

6.30

自引率

8.80%

发文量

419

审稿时长

1 months

期刊介绍： Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology features papers and reports on all aspects of drug action in humans: review articles, mini review articles, original papers, commentaries, editorials and letters. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. It also publishes research on new methods, new drugs and new approaches to treatment. The Journal is recognised as one of the leading publications in its field. It is online only, publishes open access research through its OnlineOpen programme and is published monthly.