Pharmacokinetics, toxicological and clinical aspects of ulipristal acetate: insights into the mechanisms implicated in the hepatic toxicity

Abstract

Ulipristal acetate is a drug used as emergency contraceptive (30 mg) and for the treatment of moderate to severe symptoms of uterine myomas (5 mg). After commercialization, and although the exact number is unknown, serious cases implying ulipristal acetate 5 mg as a contributing factor of liver injury, some leading to transplantation, were reported. These cases prompted to a restrict use of the drug in January 2021 by the European Medicines Agency. This work aimed to fully review pharmacokinetic aspects, namely focusing in the ulipristal acetate metabolism and other hypothetical toxicological underlying mechanisms that may predispose to drug-induced liver injury (DILI). The high lipophilicity, the extensive hepatic metabolism, the long half-life of the drug and of its major active metabolite, the long-term course of treatment, and possibility due to the formation of epoxide reactive may be contributing factors. Scientific results also points evidence to consider monitorization of liver function during ulipristal acetate treatment.

Keywords:

• Ulipristal acetate
• drug induced liver injury
• transplant
• pharmacokinetics
• metabolism

Ethical approval

All procedures were performed according to the ethical and legal standards of the institution.

Disclosure statement

The author declare that they have no conflict of interest. No writing assistance was used in the production of this manuscript.