Hepatic Safety Considerations in the Use of Ulipristal Acetate for Symptomatic Uterine Fibroids.

IF 2.8 3区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics
Therapeutics and Clinical Risk Management Pub Date : 2025-03-19 eCollection Date: 2025-01-01 DOI:10.2147/TCRM.S273358
Annika Semmler, Maria E de Lange, Joost P H Drenth, Niels S Vermeer, Pierre M Bet, Judith A F Huirne, Wouter J K Hehenkamp
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Abstract

Introduction: Ulipristal acetate (UPA, 5 mg) demonstrated efficacy in symptom reduction for patients with symptomatic fibroids. While registration and post-marketing trials assessing UPA identified few hepatic concerns, post-marketing concerns about potential drug-induced liver injury (DILI) led to significant restrictions, including indication restriction, warning labels and mandatory liver function monitoring. These measures, along with two marketing suspensions, resulted in a decline in UPA use, ultimately leading to the withdrawal of its marketing authorization previously in Canada, Australia, as well as Singapore and in 2024, at the request of the marketing authorization holder for commercial reasons, also for the European Union.

Methods: This narrative review critically evaluates the hepatic safety considerations associated with UPA.

Results: On reassessment, the risk of severe DILI with UPA is low at 13.5:100.000, with an incidence of 1 in 200,000 for liver transplantation. These numbers are lower than with many other widely prescribed medications, where no regular liver monitoring is recommended. UPA was subjected to strict liver test monitoring although proof of effectiveness of these measures in preventing serious DILI was lacking. While the risk of severe hepatotoxic events is important to consider, a balanced approach to safety measures is needed, particularly in light of the higher risks associated with alternative treatment options such as surgical intervention.

Conclusion: While UPA had a unique place in the treatment of uterine fibroids, overly cautious regulatory measures due to exceedingly rare DILI incidences led to the withdrawal of its marketing authorization in most parts of the world. There is a need for an improved understanding of DILI mechanisms and causality assessments to aid in the development of more proportional regulatory responses, balancing patient safety and sustained access to effective innovative treatment.

使用醋酸乌普利司特治疗症状性子宫肌瘤的肝脏安全考虑。
简介:醋酸乌普利司妥(UPA, 5mg)对症状性肌瘤患者的症状减轻有疗效。虽然注册和上市后试验评估UPA发现了很少的肝脏问题,但上市后对潜在药物性肝损伤(DILI)的担忧导致了重大限制,包括适应症限制、警告标签和强制性肝功能监测。这些措施,加上两次上市暂停,导致UPA使用量下降,最终导致其先前在加拿大、澳大利亚和新加坡的上市许可被撤销,并于2024年应上市许可持有人出于商业原因的要求,在欧盟也被撤销。方法:这篇叙述性综述批判性地评估了与UPA相关的肝脏安全考虑。结果:重新评估时,UPA合并严重DILI的风险较低,为13.5:10万,肝移植发生率为20万分之一。这些数字低于许多其他广泛使用的处方药,这些处方药不建议定期监测肝脏。UPA受到严格的肝脏检查监测,尽管缺乏这些措施在预防严重DILI方面有效性的证据。虽然需要考虑严重肝毒性事件的风险,但需要采取平衡的安全措施,特别是考虑到与外科手术等替代治疗方案相关的较高风险。结论:虽然UPA在子宫肌瘤治疗中具有独特的地位,但由于DILI发病率极其罕见,监管措施过于谨慎,导致其在世界大部分地区被撤回上市许可。有必要更好地了解DILI机制和因果关系评估,以帮助制定更相称的监管反应,平衡患者安全和持续获得有效的创新治疗。
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来源期刊
Therapeutics and Clinical Risk Management
Therapeutics and Clinical Risk Management HEALTH CARE SCIENCES & SERVICES-
CiteScore
5.30
自引率
3.60%
发文量
139
审稿时长
16 weeks
期刊介绍: Therapeutics and Clinical Risk Management is an international, peer-reviewed journal of clinical therapeutics and risk management, focusing on concise rapid reporting of clinical studies in all therapeutic areas, outcomes, safety, and programs for the effective, safe, and sustained use of medicines, therapeutic and surgical interventions in all clinical areas. The journal welcomes submissions covering original research, clinical and epidemiological studies, reviews, guidelines, expert opinion and commentary. The journal will consider case reports but only if they make a valuable and original contribution to the literature. As of 18th March 2019, Therapeutics and Clinical Risk Management will no longer consider meta-analyses for publication. The journal does not accept study protocols, animal-based or cell line-based studies.
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