EMA approves Ulipristal for Preop Treatment of Uterine Fibroids

The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) grants marketing authorization for Ulipristal Acetate (Gedeon Richter) as pre-operative treatment for uterine fibroids.

Ulipristal is a selective progesterone receptor modulator used for intermittent treatment for moderate to severe symptoms of uterine fibroids in women of reproductive age. It is also used as a pre-operative treatment in women scheduled for a uterine fibroid surgery, where it helps reduce bleeding, anemia and fibroid size. It will be available as 5 mg tablet upon approval.

The application for ulipristal approval was an informed consent application, which means that reference is made to an already authorized medication upon obtaining consent to the use of their dossier in the application procedure. The reference product for Gedeon Richter Ulipristal was Esmya.

The approval further recommends that the drug should only be prescribed by physicians who are experienced in the treatment of fibroids. The common side effects of the drug include endometrial thickening, amenorrhea, and hot flushes.

However, European Union drug regulators have expressed concerns about the side effects on the liver by Esmya in the past. In December 2017, the EMA opened an investigation about liver injury by the drug, followed by a monthly recommendation of liver function test in women taking Esmya by the EMA's Pharmacovigilance Risk Assessment Committee (PRAC).

Meanwhile, the United States FDA announced in February 2018 that it had extended the review of ulipristal new drug application (NDA) to August 2018.

  

Committee Statement

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EMA/PRAC recommends removal of modified release paracetamol from the market.

European Union Regulator agency European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has recommended that modified- or prolonged-release form of popular painkiller paracetamol should be removed from market.

The recommendation was based on results of a literature review that found out that these medicines behave in a complex way in cases of overdosing, and the amount of drug release cannot be predicted. The complex pharmacokinetics in cases of overdosing might result in severe liver damage or death. 

The review was conducted following a request by Swedish medicines authority, the Medical Products Agency, which had noted problems in managing overdose with such a product since marketing approval.

"Experience has shown that in overdose (particularly at high doses), because of the way the paracetamol in modified-release products is released in the body, the usual treatment procedures developed for immediate-release products are not appropriate," the EMA said in the news release.

The matter is much more complicated if the product also contains Tramadol, because of the additional effect of overdosing with Tramadol too.

This is of particular concern in cases when the physician is unaware that modified release paracetamol has been taken, which affects decisions such as when and for how long to give an antidote.

The PRAC committee could not identify means to reduce the harm to patients or design a standard and feasible protocol to manage overdoing, that could be easily adapted across whole of European Union. The committee finally concluded that the risk involved with overdosing outweighs the benefits offered by modified or extended release preparations.

The Committee therefore recommended that, “The marketing of modified-release paracetamol medicines should be suspended. Immediate-release paracetamol products, which are not affected by this review, will continue to be available as before.”

The PRAC recommendations will be sent to the Co-ordination Group for Mutual Recognition and Decentralised Procedures–Human (CMDh), which will review the matter and release a position statement on the issue.

Full text of EMA statement.