Temporary suspension of the sales of Esmya™ (ulipristal acetate) Tablet 5mg
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The Health Sciences Authority (HSA) would like to update healthcare professionals on the temporary suspension of the sales of Esmya™ (ulipristal acetate) Tablet 5mg, used for the treatment of uterine fibroids. This is due to ongoing concerns of its association with liver injuries, the most recent of which involved an overseas report of serious liver injury resulting in liver transplantation that was surfaced by the European Medicines Agency (EMA).
Background on the European Medicines Agency’s review and temporary suspension of the use of Esmya™
In 2018, the EMA had conducted a safety review on the risk of serious liver injury with Esmya™, which concluded that there was a risk of rare but serious liver injury with the medicine. As a result, additional measures, such as contraindicating the use of Esmya™ in patients with underlying liver disorders, more frequent liver function monitoring and restricting the use of multiple courses of the product in women who are not eligible for surgery, were put in place to manage this risk. As a new case of serious liver injury resulting in liver transplantation had occurred despite these measures, the EMA has restarted a review to determine if the previous risk minimisation measures were adequate to manage this safety concern.1
The EMA’s review is restricted only to ulipristal acetate 5mg for the treatment of uterine fibroids and does not affect the use of ulipristal acetate 30mg as a single-dose medicine for emergency contraception, as there is currently no concern about liver injury with the latter.
Local situation and regulatory actions taken to date
Esmya™ has been registered for use in Singapore since November 2014, for the pre-operative or intermittent treatment of uterine fibroids in adult women of reproductive age. Since 2017, HSA has been closely monitoring the overseas reports of rare but serious liver injuries associated with Esmya™.
In 2018, HSA conducted a benefit-risk assessment on the risk of rare but serious liver injury associated with the use of Esmya™ in the treatment of uterine fibroids. It was assessed that the benefits of Esmya™ continue to outweigh the risks of serious liver injury (approximately 1 in 95,000 patients) for its locally approved use, with the implementation of additional risk mitigation measures. These measures include: a) contraindicating the use in patients with underlying liver disorders, b) restricting the use of multiple treatment courses in women who are not eligible for surgical treatment and, c) increasing the frequency of liver function monitoring. These measures were communicated to healthcare professionals via the company’s Dear Healthcare Professional Letter in April 20192 and a publication in the September 2019 issue of the HSA ADR News Bulletin.3 A patient information brochure was also developed and disseminated by the company, to advise patients on the potential risk of serious liver injury and the signs and symptoms to look out for, during treatment with Esmya™. To-date, HSA has not received any local adverse drug reaction reports of serious liver injury, or liver failure, associated with Esmya™ treatment in Singapore.
Following the recent overseas case report of serious liver injury with Esmya™, HSA is working with the company to implement the temporary suspension of the sales of Esmya™ as a precautionary measure, while HSA’s reassesses the benefit versus risk profile of the product. In the interim, HSA is recommending the following advisory.
Healthcare professionals are advised:
- to assess the conditions of their patients to determine if a switch to alternative therapies may be appropriate
- to advise patients to monitor for signs and symptoms of liver injury (e.g. yellowing of the skin, fatigue or excessive tiredness, nausea and vomiting), and to contact their doctors immediately if they develop these signs and symptoms
- to monitor the liver function of patients who have been prescribed Esmya™, including two to four weeks after stopping treatment
- not to start new patients on Esmya™
HSA will take the necessary actions to safeguard public health and keep healthcare professionals updated on the outcome of our review.