Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Drug Saf. 2020 Dec;43(12):1267-1276. doi: 10.1007/s40264-020-00960-1.
Ulipristal acetate (ulipristal) is a selective progesterone receptor modulator that has been marketed for daily use in Europe and Canada to reduce symptoms caused by uterine fibroids. Long-term use of some other members of this class of 19-norprogesterone-derived agents has been associated with idiosyncratic hepatotoxicity.
We analyzed postmarketing reports of suspected drug-induced liver injury associated with the daily use of 5 mg of ulipristal to treat symptoms of uterine fibroids.
We searched for reports of serious liver injury associated with ulipristal, submitted to the US Food and Drug Administration through 31 January, 2020. Cases of liver injury temporally associated with long-term ulipristal exposure that reported combined increases of serum aminotransferases and bilirubin were individually assessed using a five-tier categorical scale of likelihood for a causal association with the drug by individuals with expertise in drug-induced liver injury evaluation. Individual cases that did not culminate in liver failure, death, or liver transplantation were also assessed for their causal association with ulipristal by the Roussel Uclaf Causality Assessment Method.
We identified nine non-US cases that met the criteria for inclusion in our search for cases of serious liver injury associated with ulipristal. Five cases reported clinical outcomes of liver transplantation and/or death and all were assessed to have a probable causal association with ulipristal acetate. Evaluation of the other four cases reporting resolution of liver injury after treatment discontinuation revealed a possible or probable causal relationship with ulipristal.
We identified postmarketing cases of serious acute drug-induced liver injury causally associated with ulipristal used to treat uterine fibroids, some with outcomes of liver transplant and/or death. The presence of common structural features identified with certain selective progesterone receptor modulators in the treatment of chronic conditions may indicate a liability for idiosyncratic drug-induced liver injury.
醋酸乌利司他（ulipristal）是一种孕激素受体选择性调节剂，在欧洲和加拿大已被批准用于日常使用，以减轻子宫肌瘤引起的症状。长期使用该类其他一些成员的 19-去甲孕酮衍生药物与特发性肝毒性有关。
我们分析了与每日使用 5 毫克乌利司他治疗子宫肌瘤症状相关的疑似药物性肝损伤的上市后报告。
我们通过美国食品和药物管理局搜索了截至 2020 年 1 月 31 日与乌利司他相关的严重肝损伤报告。使用具有药物性肝损伤评估专业知识的个人，根据与药物的因果关系的可能性，对与长期乌利司他暴露时间相关且报告血清转氨酶和胆红素联合升高的肝损伤病例进行单独评估，使用五等级分类量表。对未导致肝衰竭、死亡或肝移植的个别病例，也使用 Roussel Uclaf 因果关系评估方法评估其与乌利司他的因果关系。
我们确定了 9 例非美国病例，符合我们搜索与乌利司他相关的严重肝损伤病例的标准。5 例报告了肝移植和/或死亡的临床结果，所有病例均被评估为与醋酸乌利司他具有可能的因果关系。对另外 4 例报告治疗停止后肝损伤消退的病例进行评估显示，与乌利司他存在可能或可能的因果关系。
我们发现了与治疗子宫肌瘤的乌利司他相关的上市后严重急性药物性肝损伤病例，其中一些病例的结局为肝移植和/或死亡。在治疗慢性疾病时使用的某些孕激素受体选择性调节剂具有共同的结构特征，这可能表明其具有特发性药物性肝损伤的易感性。
