Joint EMAS, IMS and ESSM response to EMA advice regarding high-strength estradiol vaginal creams

The European Medicine Agency on October 4th warned both consumers and prescribers against the use of high-strength estradiol creams for longer than 4 weeks [1]. These high dose creams are marketed in Austria, Bulgaria, Croatia, Czech Republic, Estonia, Germany, Hungary, Latvia, Lithuania and Slovakia.

Genitourinary syndrome of menopause affects more than half of postmenopausal women. The syndrome comprises of genital, urinary and sexual symptoms, which have a significant impact on health and quality of life. While the high-strength preparations included in the EMA recommendation may increase the circulating concentrations of estradiol, those currently in use in most of Europe and worldwide provide much lower doses, with negligible effects on systemic levels. The safety of these low-dose preparations has been confirmed by many studies, which have shown no adverse effects.

Given the prevalence of genitourinary syndrome of menopause and the efficacy and safety of low-dose preparations in current use, the European Menopause and Andropause Society (EMAS), the International Menopause Society (IMS) and the European Society for Sexual Medicine (ESSM) recommend that low-dose preparations should continue to be used in women who need them.

Antonio Cano, EMAS President

Susan Davis, IMS President

Yacov Reisman – ESSM President

References

EMA Four-week limit for use of high-strength estradiol creams  4 October 2019 EMA/531250/2019 :
https://www.ema.europa.eu/en/documents/referral/estradiol-containing-001-w/w-medicinal-products-topical-use-article-31-referral-four-week-limit-use-high-strength-estradiol_en.pdf.

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).

Human medicines: regulatory information
https://www.ema.europa.eu/en/human-medicines-regulatory-information

Brexit-related guidance for companies
From Lab to Patient: The journey of a medicine assessed by EMA

Therapeutic areas: latest updates