Temporary suspension of sales of Esmya™ (ulipristal acetate) tablet 5 mg (Sep 2020)
This safety alert contains new/additional information to the previous posting dated 2 Apr 2020.
The Health Sciences Authority (HSA) would like to inform healthcare professionals about the temporary suspension of the sales of Esmya™ (ulipristal acetate) tablet 5 mg, used for the treatment of symptoms of uterine fibroids. The sales of Esmya™ has been temporarily suspended in Singapore since March 2020 as a precautionary measure, while HSA conducts a reassessment on the benefit-risk profile of Esmya™.1 This was due to ongoing concerns of its association with liver injury, including overseas reports of serious liver injury resulting in liver transplantations that were surfaced by the European Medicines Agency (EMA).
EMA’s review and recommendation to revoke the marketing authorisation of ulipristal acetate tablet 5 mg in the European Union
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 product. 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 restarted a review in March 2020, to determine if the previous risk minimisation measures were adequate to manage this safety concern.2
The EMA’s review was restricted only to ulipristal acetate 5 mg for the treatment of symptoms of uterine fibroids and did not affect the use of ulipristal acetate 30 mg as a single-dose medicine for emergency contraception, as there was no concern about liver injury with the latter. In September 2020, the EMA completed its review of this safety concern, and recommended the revocation of the marketing authorisation of all ulipristal acetate 5 mg products, including Esmya™. The EMA’s review took into consideration the reported cases of serious liver injury, as well as the inputs of patient and healthcare professional representatives, including experts in gynaecology. As it was not possible to identify which patients were most at risk of liver injury, or the measures which could reduce this risk, the EMA concluded that the risks of using ulipristal acetate 5 mg for the treatment of symptoms of uterine fibroids outweighed their benefits. Therefore, the EMA recommended that these products should no longer be marketed in the European Union.3
Esmya™ has been registered for use in Singapore since November 2014, for the pre-operative or intermittent treatment of symptoms 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 symptoms of uterine fibroids. It was assessed that the benefits of Esmya™ continued 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 20194 and a publication in the September 2019 issue of the HSA ADR News Bulletin.5 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.
HSA’s regulatory actions
Following the notification of an overseas case report of serious liver injury with Esmya™ leading to liver transplantation despite the implementation of risk minimisation measures, HSA has worked with the company to implement the temporary suspension of the sales of Esmya™ in March 2020 as a precautionary measure, while HSA reassesses the benefit versus risk profile of the product. In the interim, HSA has also issued an advisory for healthcare professionals, including assessing if a switch to alternative therapies was appropriate for their patients, monitoring the liver function of patients who have been prescribed Esmya™, and not to start new patients on Esmya™.
HSA’s reassessment of the benefit-risk profile of Esmya™ is currently ongoing, and our review will take into consideration the latest information from overseas developments. We will keep healthcare professionals updated on the outcomes of our review when completed.