Estradiol-containing (0.01% w/w) medicinal products for topical use

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CMDh position
  • European Commission final decision
Current status:
Recommendation provided by Pharmacovigilance Risk Assessment Committee

Overview

Update of 31 October 2019:

Following the PRAC’s recommendation of 3 October 2019, one of the marketing authorisation holders involved with this review has requested a re-examination. Upon receipt of the grounds for the request, the PRAC will start a re-examination, which is expected to conclude at the PRAC meeting of 13-16 January 2020.

 

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.

Key facts

About this medicine
Approved name
Estradiol-containing (0.01% w/w) medicinal products for topical use
International non-proprietary name (INN) or common name

 estradiol

Associated names
  • Linoladiol
  • Linoladiol N
  • Linoladiol Estradiol
  • Estradiol Wolff
  • Montadiol
Class
Hormonal
About this procedure
Current status
Recommendation provided by Pharmacovigilance Risk Assessment Committee
Reference number
EMEA/H/A-31/1482
Type
Article 31 referrals

This type of referral is triggered when the interest of the Union is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.

Decision making model
PRAC-CMDh
Authorisation model
Nationally authorised product(s)
Key dates and outcomes
Procedure start date
11/04/2019
PRAC recommendation date
03/10/2019
Outcome
Risk minimisation measures

All documents

Procedure started

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Document description

  • Annex I - List of the medicines affected by the referral
  • Annex II - Scientific conclusions of the CHMP or CMDh
  • Annex III - Changes to the summary of product characteristics, labelling or package leaflet - available when the CHMP or CMDh recommends changes to the product information. Also includes conditions for lifting of suspensions, if applicable
  • Annex IV - Conditions of the marketing authorisation - available when the CHMP or CMDh recommends other measures to be taken for the marketing authorisation such as safety measures or additional studies
  • Notification - A letter from a Member State, the European Commission or a marketing-authorisation holder requesting the initiation of a referral procedure
  • Rationale for triggering - Background provided by the party triggering the referral explaining the issues leading to the initiation of the procedure
  • PRAC list of questions - Questions agreed by the PRAC requesting further information to evaluate the issues identified
  • PRAC timetable - Timeframe agreed by the PRAC to receive information, assess the issues and adopt a recommendation
  • PRAC / CHMP or CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

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