Ulipristal acetate is a progesterone receptor modulator that has previously been approved as a postcoital contraceptive; has subsequently been licensed for the treatment of fibroids
- as progesterone promotes the growth of uterine fibroids, blocking its receptor may reduce their size. The dose used for this indication can inhibit ovulation and lead to amenorrhoea which will be of benefit to women who have heavy menstrual bleeding related to their fibroids
- extensive metabolism involving cytochrome P450 3A4
- ullipristal should therefore not be taken with inducers of this enzyme, such as carbamazepine, phenytoin and St John's wort, or with inhibitors such as erythromycin
- half-life of ulipristal is about 38 hours with most of the metabolites being excreted in the faeces. No studies have been done in women with impaired hepatic or renal function
Gedeon Richter Plc. in agreement with the European Medicines Agency (EMA), and the Medicines and Healthcare product Regulatory Agency (MHRA) would like to inform you about new restrictions on the use of ulipristal acetate 5 mg and additional measures to minimise the risk of serious liver injury (1):
Summary
- Cases of serious liver injury (including those necessitating liver transplantation) have followed the use of ulipristal acetate 5 mg for treating moderate to severe symptoms of uterine fibroids.
- Ulipristal acetate 5 mg must now be used only for intermittent treatment of moderate to severe symptoms of uterine fibroids in women who have not reached menopause and when uterine fibroid embolisation or surgery are not suitable or have failed.
- The physician must discuss with patients the risks and benefits of available alternative treatments so patients can make an informed decision.
- The risks of ulipristal acetate 5 mg should be fully explained to patients, especially the risk of liver injury, which could in rare cases lead to liver transplantation.
- Patients should be informed about possible signs and symptoms of liver injury, and that if they have such symptoms, they must stop treatment and contact their doctor immediately
" The marketing of ulipristal acetate 5mg was suspended while a second European review of the risk of liver injury took place. The review concluded that in addition to the previous measures, the indication of ulipristal acetate 5 mg should be further restricted. The risk of severe liver injury does not justify its use for pre-operative treatment of uterine fibroids.
Prior to prescribing, the prescriber must carefully explain the benefits and risks of ulipristal acetate 5 mg to patients as well as the benefits and risks of alternative treatments so that the patient can make a fully informed decision about the treatment which is most appropriate for her. In particular patients should be told about the risk of liver injury which has in rare cases required liver transplant. Patients should be told the signs and symptoms of liver injury and that if they experience such symptoms, they should stop treatment and contact their doctor immediately. Patients should also be informed of the need for liver monitoring before, during and after treatment courses. For this reason, patients should carefully read the patient alert card included in the medicine’s package.
These measures will be introduced in the summary of product characteristics (SmPC) of ulipristal acetate 5 mg. The Physician’s guide and the patient alert card will also be updated.. (1)"
NICE had previously suggested (2):
- if fibroids 3 cm or more in diameter:
- f ulipristal acetate is the preferred treatment option, be aware of measures to reduce the risk of rare but serious liver injury:
- discuss the relative benefits and harms of ulipristal acetate with women, including recognising the signs and symptoms of liver injury, to enable an informed decision
- monitor liver function for the first 2 treatment courses, and as clinically indicated, in line with current prescribing guidance
- when ulipristal is used for intermittent treatment in women who are not eligible for surgery, for example where the risks of surgery outweigh the benefits or where the woman declines surgical treatment:
- offer ulipristal acetate 5 mg (up to 4 courses) to women with heavy menstrual bleeding and fibroids of 3 cm or more in diameter, and a haemoglobin level of 102 g per litre or below
- consider ulipristal acetate 5 mg (up to 4 courses) for women with heavy menstrual bleeding and fibroids of 3 cm or more in diameter, and a haemoglobin level above 102 g per litre
- NICE noted that (2) "..be aware that the effectiveness of pharmacological treatments for HMB (excluding ulipristal acetate) may be limited in women with fibroids that are substantially greater than 3 cm in diameter.."
Reference:
- Gedeon Richter UK Ltd. (January 29th 2021). Direct Healthcare Professional Communication. Esmya (ulipristal acetate) 5 mg: Indications for uterine fibroids restricted due to concerns of severe liver injury
- NICE (November 2018). Heavy menstrual bleeding