Four-week limit for use of high-strength estradiol creams

EMA’s safety committee (PRAC) has recommended limiting the use of high-strength creams containing 100 micrograms/gram (0.01%) of estradiol to a single treatment period of up to 4 weeks. This measure is intended to minimise the risk of side effects caused by estradiol absorbed into the bloodstream from creams applied inside the vagina to treat symptoms of vaginal atrophy in women who have been through menopause.

The PRAC has reviewed available data on the safety and effectiveness of high-strength estradiol-containing creams, including data on the amount of estradiol in the blood. These data showed that in postmenopausal women who had used these creams, the levels of estradiol in the blood were higher than normal postmenopausal levels. The PRAC concluded that absorption of estradiol into the bloodstream is of concern and could result in similar side effects to those seen with hormone replacement therapy (HRT). The side effects of HRT taken orally or used transdermally (as patches) include venous thromboembolism (formation of blood clots in the veins), stroke, endometrial cancer (cancer of the lining of the womb) and breast cancer. In the absence of safety data for long-term use of high-strength estradiol creams, the PRAC recommended that these creams should only be used for a single treatment period of a maximum of 4 weeks.

The prescribing information for these creams will be updated with the new recommendations. A warning that the medicine is to be used for a single treatment period of up to 4 weeks only will be placed on the outer and inner packaging and the size of the tube will be limited to 25 grams to prevent use for longer than recommended.

The PRAC recommendations will now be sent to the CMDh1 to make a decision about their implementation. The CMDh is a body representing EU Member States as well as Iceland, Liechtenstein and Norway.


1Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human.

Questions & answers: EU actions to prevent medicine shortages due to Brexit

EMA has published a questions-and-answers (Q&A) document for patients, healthcare professionals and the general public on the preparatory work that European Union authorities are doing to prevent medicine-shortages due to the United Kingdom’s withdrawal from the EU.

It explains that in case of a withdrawal agreement, there will be a transition period during which EU law will continue to apply in the United Kingdom. This means that access to medicines will not be affected.

If the UK leaves without a withdrawal agreement or deal (‘no-deal scenario’), EU law will cease to apply in the UK. In this case, in order to be able to continue to supply medicines in the EU, companies carrying out certain activities in the UK will need to make changes to comply with EU law.

The Q&As explain how EMA, the European Commission and EU/EEA Member States have been working closely together since May 2017 to advise companies on how to apply for the necessary changes in order to minimise the impact on the supply of medicines, if the UK leaves the EU without a withdrawal agreement.

The document underlines that Brexit will not impact the safety of medicines, nor the way they are evaluated. EMA and the Member States will continue to monitor the safety and efficacy of medicines without any changes.

This document applies to both human and veterinary medicines and will be updated as necessary.

Industry preparations for new Brexit deadlines

In view of the conclusion of the European Council on 22 March to extend the date of the withdrawal of the UK from the EU, EMA calls on all pharmaceutical companies in the EU to continue their preparedness activities, taking into account all possible outcomes. Based on the European Council conclusions, the deadline of 29 March referred to in EMA’s published Brexit-related guidance should be understood to be replaced by 12 April 2019 until further notice.

Further information is available by clicking here.

For more information on the European regulatory system for medicines, please click here. (brochure available in all languages).

Omega-3 fatty acid medicines no longer considered effective in preventing heart disease

EMA has concluded that omega-3 fatty acid medicines are not effective in preventing further heart and blood vessels problems in patients who have had a heart attack. The conclusion, based on a review of data accumulated over the years, means that these medicines will no longer be authorised for such use.

Omega-3 fatty acid medicines have been authorised for use after a heart attack, in combination with other medicines, in several EU countries since 2000, at a dose of 1 g per day. At the time of their authorisation, available data showed some benefits in reducing serious problems with the heart and blood vessels, although the benefits were considered modest. Further data that have become available since then have not confirmed the beneficial effects of these medicines for this use.

Although there are no new safety concerns, EMA’s human medicines committee (CHMP) concluded that the balance between the benefits and risks of these medicines to prevent recurrence of heart disease or stroke is now negative.

These medicines can still be used to reduce levels of certain types of blood fat called triglycerides.

Further information, including specific information for patients and healthcare professionals, is available by clicking here<https://www.ema.europa.eu/en/medicines/human/referrals/omega-3-fatty-acid-medicines>. For more information on the European regulatory system for medicines, please click here<https://www.ema.europa.eu/about-us/how-we-work/european-medicines-regulatory-network> (brochure available in all languages).

EMA Consultation: Draft guideline on safety and efficacy follow-up and risk management of advanced therapy medicinal products – Revision 1

The European Medicines Agency has released for public consultation a draft guideline on safety and efficacy follow-up and risk management of advanced therapy medicinal products – Revision 1.

The aim of this guideline is to provide the guidance for the Safety and Efficacy (S&E) follow-up and risk management for advanced therapy medicinal products (ATMPs) according to Article 14(4) of Regulation (EC) No 1394/2007. This regulation requires the European Medicines Agency (EMA) to develop a detailed guideline relating to the post-authorisation follow-up of efficacy and adverse reactions, and risk management for these products.

This is the 1st revision of the original ATMP guideline on safety and efficacy follow-up and risk management; the guideline has been revised to take into consideration the experience gained with the authorisation of these products and to define their risks and their risk minimisations measures. In addition, guidance on methodology in order to design post-authorisation S&E follow-up studies is provided.

The draft guideline is available by clicking here.

Comments should be provided using this template and sent to atmpguideline@ema.europa.eu by 30/04/2018.

Please note that EMA may collect and further process some personal data of stakeholders and interested parties who submit contributions to the consultations.

For more information, see Specific privacy statement for public consultations here.

For more information on the European regulatory system for medicines, please consult our brochure.

Sartan medicines: companies to review manufacturing processes to avoid presence of nitrosamine impurities

Companies that make sartan blood pressure medicines (also known as angiotensin II receptor blockers) are being required to review their manufacturing processes so that they do not produce nitrosamine impurities.

These recommendations follow EMA’s review of N-nitrosodimethylamine (NDMA) and N‑nitrosodiethylamine (NDEA), which are classified as probable human carcinogens (substances that could cause cancer) and have been detected in some sartan medicines.

For the vast majority of sartan medicines, impurities were either not found or were present at very low levels.

The review estimated the highest possible cancer risk with these impurities. It concluded that if 100,000 patients took valsartan from Zhejiang Huahai<https://www.ema.europa.eu/en/news/ema-reviewing-medicines-containing-valsartan-zhejiang-huahai-following-detection-impurity-some> (where the highest levels of impurities were found) every day for 6 years at the highest dose, there could be 22 extra cases of cancer due to NDMA over the lifetimes of those 100,000 patients. NDEA in these medicines could lead to 8 extra cases in 100,000 patients taking the medicine at the highest dose every day for 4 years.[1] The estimates have been extrapolated from animal studies and are very low compared with the lifetime risk of cancer in the EU (1 in 2).

Further information, including specific information for patients and healthcare professionals, is available by clicking here.

For more information on the European regulatory system for medicines, please click here (brochure available in all languages).

EMA launches new corporate website

The European Medicines Agency (EMA) has launched a new version of its corporate website today: https://www.ema.europa.eu/en/news/ema-launches-new-corporate-website

The website has a number of new features to improve user experience, including:

  • an improved search, allowing users to find content easily and to filter their search results. EMA plans to further refine this functionality in the future;
  • a ‘responsive’ design for cleaner display on mobile devices;
  • a simpler URLs based on the location and title of webpages or documents;
  • an updated visual design offering users a clearer reading experience and simpler navigation.

The website’s content and structure remain unchanged. Although the site’s URLs are new, URLs from the previous website will continue to work for every page and document, thanks to one-to-one redirects. Although these redirects will be available for an indefinite period, EMA encourages users who have bookmarked any URLs to consider updating them at their convenience now that the new site is live.

The new website has been designed to work optimally on the latest web browsers. EMA carried out the project to relaunch the website in collaboration with the European Commission’s Directorate General for Informatics (DIGIT).

DIGIT will also host and maintain the new website on behalf of EMA.

To provide general feedback on the new EMA’s corporate website or to make suggestions for future improvement, please write to newwebsite@ema.europa.eu. EMA will take all feedback and suggestions into account, but will not be able to reply to individual email messages.