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

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CMDh final position
Current status:
CMDh final position

Overview

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

On 16 January 2020, EMA’s safety committee (PRAC) confirmed its recommendation to limit 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 followed a re-examination of its recommendation of October 2019 which was requested by one of the companies that market high-strength estradiol cream.

The PRAC reviewed available data on the safety and effectiveness of high-strength estradiol-containing creams used to treat symptoms of vaginal atrophy in women who have been through menopause. Data on these creams show that in postmenopausal women who use them, 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 addition, there are limited safety data on long term use of high-strength estradiol creams. For these reasons, the PRAC recommended that these creams should only be used for a single treatment period of a maximum of 4 weeks.

The PRAC recommended that the prescribing information for these creams 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 were adopted by the CMDh by consensus and will be implemented directly at national level.

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
CMDh final position
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
16/01/2020
CHMP opinion/CMDh position date
30/01/2020
Outcome
Risk minimisation measures

All documents

Procedure started

  • List item

    Estradiol-containing (0.01% w/w) medicinal products for topical use Article 31 referral - Timetable (start of re-examination procedure) (PDF/139.88 KB)


    First published: 12/07/2019
    Last updated: 18/12/2019
    EMA/PRAC/214200/2019 Rev. 2

  • List item

    Estradiol-containing (0.01% w/w) medicinal products for topical use Article 31 referral - Notification (PDF/71.63 KB)


    First published: 12/04/2019

  • List item

    Estradiol-containing (0.01% w/w) medicinal products for topical use Article 31 referral - Annex I (PDF/127.58 KB)


    First published: 12/04/2019
    Last updated: 08/04/2020

  • List item

    Estradiol-containing (0.01% w/w) medicinal products for topical use Article 31 referral - PRAC list of questions (PDF/77 KB)


    First published: 12/04/2019
    EMA/PRAC/214199/2019

  • List item

    Estradiol-containing (0.01% w/w) medicinal products for topical use Article 31 referral - New review of risks with high-strength estradiol-containing creams (PDF/77.55 KB)


    First published: 12/04/2019
    EMA/215459/2019

  • Recommendation provided by Pharmacovigilance Risk Assessment Committee

    Position provided by CMDh

  • List item

    Estradiol-containing (0.01% w/w) medicinal products for topical use Article 31 referral - Four-week limit for use of high-strength estradiol creams confirmed (PDF/128.99 KB)


    First published: 31/01/2020
    Last updated: 08/04/2020
    EMA/48567/2020

  • List item

    Estradiol-containing (0.01% w/w) medicinal products for topical use Article 31 referral - Annex II (PDF/175 KB)


    First published: 08/04/2020

  • List item

    Estradiol-containing (0.01% w/w) medicinal products for topical use Article 31 referral - PRAC assessment report (PDF/554.03 KB)

    Adopted

    First published: 10/02/2020
    EMA/62697/2020

  • List item

    Estradiol-containing (0.01% w/w) medicinal products for topical use Article 31 referral - Timetable for the implementation of the CMDh position (PDF/48.5 KB)


    First published: 04/02/2020
    Last updated: 08/04/2020

  • List item

    Estradiol-containing (0.01% w/w) medicinal products for topical use Article 31 referral - Annex III (PDF/369.8 KB)


    First published: 31/01/2020
    Last updated: 08/04/2020

  • Description of documents published

    Please note that some of the listed documents apply only to certain procedures.

    • Overview - lay-language summary of the stage of the procedure
    • Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
    • Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
    • List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
    • Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
    • List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
    • List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
    • Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
    • Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
    • Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
    • Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
    • Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
    • Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
    • Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
    • Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

    Note that older documents may have different titles.

    News

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