Risk–efficacy balance of ulipristal acetate compared to surgical alternatives: How to value safety in a new drug?

Mei-An Middelkoop*, Pierre M. Bet, Joost P. H. Drenth, Judith A. F. Huirne, Wouter J. K. Hehenkamp

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review


Aims: Uterine fibroids are benign tumours that cause various complaints. These complaints may significantly compromise quality of life, necessitating a clinical intervention in 25–50% of the affected women. Hysterectomy, myomectomy or embolization may offer symptomatic relief, but are costly, include a recovery period, can cause serious side-effects, sometimes fail to treat symptoms completely and are not always desired by patients. Ulipristal is a conservative long-term treatment that has a fibroid-volume decreasing effect, acceptable side-effects while preserving fertility and may be an alternative to surgical alternatives. Currently, ulipristal is investigated by the European Medicine Agency and suspended from marketing authorization because it may cause drug-induced liver injury (DILI). However, many drugs can cause severe DILI and prospective studies estimate 14–19 DILI cases/100 000 people. Methods: This overview will discuss the risk–benefit balance between ulipristal and DILI, describe the safety–efficacy balance of ulipristal and its alternative treatments and the arguments that led to the suspension of its marketing authorization. Results: Ulipristal may be associated with DILI resulting in a risk of severe liver injury in 1.5:100 000 patients and fatal liver injury in 0.1:100 000 patients. This risk needs to be weighed against the higher mortality risk of >1:1000 and higher incidence of severe complications after surgery. Conclusion: The DILI risk of ulipristal is considerably lower than that of other medicines that are not suspended, nor need additional safety measures. When evaluating drugs and drug safety, risks that apply to the alternative nonpharmacological treatment options should be taken into consideration.
Original languageEnglish
Pages (from-to)2685-2697
Number of pages13
JournalBritish Journal of Clinical Pharmacology
Issue number7
Early online date2020
Publication statusPublished - Jul 2021

Cite this