Safety after extended repeated use of ulipristal acetate for uterine fibroids

Abstract

ObjectiveTo assess long term safety of extended repeated 3-month courses of ulipristal acetate (UPA) 10 mg/day, for up to 8 courses, with focus on endometrial and laboratory safety parameters.MethodsThis long-term, multi-center, open-label cohort, follow up study consisted of up to 8 consecutive 3-month courses of daily UPA 10 mg, each separated by a drug free period of 2 spontaneous menstrual bleeds. Sixty-four pre-menopausal women, with moderate to severe symptomatic uterine myoma(s) and heavy bleeding were enrolled and were studied for approximately 4 years. The main outcome measures were endometrial histology, laboratory parameters and general safety.ResultsAll data was reported in a descriptive manner with no formal statistical comparisons. In the 64 women, non-physiological changes (mostly cyst formation, epithelial and vascular changes) in endometrial histology at screening and after treatment courses 4 and 8 were observed in 18.0%, 21.4% and 16.3% of biopsies, respectively. After treatment cessation, such changes were observed in 9.1% of biopsies. All endometrial biopsies were benign after course 8. The median endometrial thickness was 7.0 mm, 10–18 days after the start of menses following treatment courses 5–8, compared to 9.0 mm at screening (before UPA treatment). No changes in the number and type of laboratory results outside the normal ranges were observed with the increasing treatment courses. In total, adverse events were reported in 10 (16%), 12 (19%), 8 (14%) and 5 (9%) subjects, during treatment courses 5, 6, 7 and 8, respectively of which the most frequent adverse events were headache and hot flush.ConclusionThe results of this study further support the safety profile of extended repeated 3 months treatment of symptomatic fibroids with ulipristal acetate 10 mg/day. Repeated UPA treatment courses did not result in any changes of concern in endometrial histology, endometrial thickness, or laboratory safety measures.

Uterine fibroid management: Today and tomorrow

“…The safety profile of UPA during single 26,27 and multiple 6,29,30,36 treatment courses was well documented in the four clinical RCTs and no safety issues emerged from physical examination, vital signs or electrocardiograms. The most frequently encountered side effects were hot flushes, breast pain/discomfort and headaches.…”

“…Cystic and stromal changes appear to be reversible and benign, returning to screening levels (±10%) 2 months after completion of therapy in all the PEARL studies . Moreover, in a very recent, extended PEARL III trial, neither atypical hyperplasia nor endometrial adenocarcinoma were reported in women undergoing eight courses of UPA treatment …”

“…In case of a good response, treatment can be stopped after two to four courses and the patient reassessed. Repeat therapy may be proposed if and when symptoms recur, as no endometrial hyperplasia was diagnosed in subjects given 5 mg UPA for eight courses of 3 months …”

“…UPA appears to have few serious side effects. Minor adverse events are detailed in Table , but these tend to decline with repeated courses . Trials have monitored a number of conditions arising from side effects associated with UPA, and outcomes to date (at approximately 4 years) have not identified any particular safety concerns …”

“…Repeat therapy may be proposed if and when symptoms recur, as no endometrial hyperplasia was diagnosed in subjects given 5 mg UPA for eight courses of 3 months. 36…”