Ulipristal Acetate (DB08867): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Ulipristal Acetate (UPA) is a synthetic steroid and a selective progesterone receptor modulator (SPRM) that has carved out a distinct and dichotomous legacy in modern women's health. Marketed under different brand names and dosages for two separate indications, its clinical history represents both a significant therapeutic advancement and a profound cautionary tale. As a single 30 mg dose for emergency contraception (EC), sold primarily as Ella and ellaOne, UPA is recognized as a first-line therapy, demonstrating superior efficacy and a longer window of action—up to 120 hours post-intercourse—compared to the older levonorgestrel-based options.[1] Its mechanism, primarily involving the delay or inhibition of ovulation, has been a cornerstone of its success and widespread adoption, including its switch to over-the-counter status in much of Europe.[3]

In stark contrast, the journey of UPA as a 5 mg daily tablet for the treatment of uterine fibroids, marketed as Esmya and Fibristal, has been fraught with controversy. Initially lauded for its ability to effectively control bleeding and reduce fibroid volume, offering a much-needed oral alternative to surgery or injectable GnRH agonists, its long-term use was derailed by post-marketing surveillance data.[4] Reports emerged of rare but severe, unpredictable cases of drug-induced liver injury (DILI), some necessitating liver transplantation.[4] This critical safety signal, which could not be linked to identifiable patient risk factors, prompted a cascade of regulatory actions by the European Medicines Agency (EMA), including temporary suspensions, severe usage restrictions, and ultimately, the withdrawal of its marketing authorization in Europe and other jurisdictions for commercial reasons stemming from the safety concerns.[7] The U.S. Food and Drug Administration (FDA) never approved the fibroid in