Semmler Annika, de Lange Maria E, Drenth Joost P H, Vermeer Niels S, Bet Pierre M, Huirne Judith A F, Hehenkamp Wouter J K
Amsterdam Reproduction & Development Research Institute, Amsterdam, the Netherlands.
Department of Obstetrics and Gynecology, Amsterdam University Medical Center, location AMC and VUMC, Amsterdam, the Netherlands.
Ther Clin Risk Manag. 2025 Mar 19;21:367-382. doi: 10.2147/TCRM.S273358. eCollection 2025.
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.
This narrative review critically evaluates the hepatic safety considerations associated with UPA.
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.
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.
醋酸乌利司他（UPA，5毫克）已证明对有症状的子宫肌瘤患者在减轻症状方面有效。虽然评估UPA的注册试验和上市后试验发现肝脏方面的问题较少，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、警示标签和强制性肝功能监测。这些措施，再加上两次市场暂停，导致UPA的使用量下降，最终导致其在加拿大、澳大利亚以及新加坡先前已撤回上市许可，并且在2024年，应上市许可持有人的商业请求，在欧盟也撤回了上市许可。
本叙述性综述批判性地评估了与UPA相关的肝脏安全性考量。
重新评估后，UPA导致严重DILI的风险较低，为13.5:100,000，肝移植发生率为1/200,000。这些数字低于许多其他广泛处方的药物，而对于这些药物并不建议进行定期肝脏监测。尽管缺乏这些措施在预防严重DILI方面有效性的证据，但UPA仍受到严格的肝脏检测监测。虽然严重肝毒性事件的风险很重要，但需要采取平衡的安全措施，特别是考虑到手术干预等替代治疗选择存在更高风险。
虽然UPA在子宫肌瘤治疗中曾占有独特地位，但由于极为罕见的DILI发生率而采取的过度谨慎的监管措施导致其在世界大部分地区撤回上市许可。需要更好地理解DILI机制和因果关系评估，以帮助制定更适度的监管应对措施，平衡患者安全和持续获得有效的创新治疗。
