Intermittent treatment with Esmya involves patients taking one 5mg tablet daily for up to 3 months, starting during the first week of menstruation. In studies, intermittent treatment was evaluated for up to four 3-month courses.
Periodic monitoring of the endometrium is recommended in patients treated intermittently with Esmya. This should take place during a treatment off-period after menstruation has resumed. Monitoring should include an annual ultrasound and, if endometrial thickening is observed, a biopsy should be performed to rule out endometrial malignancy.
Ulipristal acetate usually leads to a significant reduction in menstrual blood loss or amenorrhoea within the first 10 days of treatment. A biopsy is recommended if any unexpected bleeding or an altered bleeding pattern is subsequently experienced.
Two phase III studies assessed use of ulipristal acetate for up to four intermittent 3-month treatment courses in patients with heavy menstrual bleeding associated with uterine fibroids.
Reduced menstrual bleeding
PEARL III was an open-label study evaluating ulipristal acetate 10mg once daily, in which each 3-month treatment period was followed by 10 days of double-blind treatment with norethisterone acetate or placebo. In this study, efficacy was shown for up to 18 months of intermittent treatment, with 79.5% of women (105 of 132) in amenorrhoea (primary endpoint) after the first treatment course and 89.7% (96 of 107) in amenorrhoea at the end of the fourth treatment course.
PEARL IV was a randomised, double-blind study assessing ulipristal acetate 5mg or 10mg in 451 women. In total, 61.9% of patients in the 5mg group and 72.7% of those in the 10mg group were in amenorrhoea at the end of both treatment courses 1 and 2 (p=0.032); 48.7% and 60.5%, respectively, were in amenorrhoea at the end of all four treatment courses (p=0.027). After four treatment courses, there was no significant difference in the frequency of amenorrhoea between the two dose groups (p=0.290).
Both dose regimens of ulipristal acetate effectively controlled menorrhagia, with 81.1% of patients on the 5mg dose achieving controlled bleeding (as defined by no episodes of heavy bleeding and a maximum of 8 days of bleeding during the last 56 days of a treatment course) at the end of two treatment courses.
After the second treatment course, fibroid volume (based on the three largest fibroids) was reduced by a median of 54.1% and 58.0% in the patients receiving ulipristal acetate 5mg and 10mg, respectively (p=0.06). Patients also reported substantial improvements in pain and quality of life during treatment, and these improvements were partly maintained during the off-treatment period.
The investigators concluded that the 5mg dose of ulipristal acetate approved for pre-operative use would be appropriate for long-term symptom management.
In all phase III studies of ulipristal acetate in the treatment of fibroids, a total of 7 cases of hyperplasia were observed out of 789 patients with adequate biopsies (0.89%). Most of these spontaneously reverted to normal endometrium after resumption of menstruation during the off-treatment period. The incidence of hyperplasia in patients treated with ulipristal acetate is consistent with that in symptomatic pre-menopausal women and did not increase with repeated treatment courses.
Intermittent treatment with ulipristal acetate was generally well tolerated. The most frequent adverse reactions were hot flush, headache, nasopharyngitis and abdominal pain.