Nomegestrol and chlormadinone

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CHMP opinion
  • European Commission final decision
Current status
European Commission final decision

Overview

New measures to minimise risk of meningioma with medicines containing nomegestrol or chlormadinone

On 1 September 2022, EMA’s human medicines committee (CHMP) endorsed the recommendation of the Pharmacovigilance Risk Assessment Committee (PRAC), which concluded that the benefits of medicines containing nomegestrol or chlormadinone outweigh the risks, provided new measures are taken to minimise the risk of meningioma.

A meningioma is a tumour of the membranes covering the brain and spinal cord. It is usually benign and is not considered to be a cancer, but due to their location in and around the brain and spinal cord meningiomas can in rare cases cause serious problems.

The CHMP recommended that medicines containing high-dose nomegestrol (3.75 – 5 mg) or high-dose chlormadinone (5 – 10 mg) should be used at the lowest effective dose and for the shortest duration possible, and only when other interventions are not appropriate. In addition, low- and high-dose nomegestrol- or chlormadinone-containing medicines must not be used by patients who have, or have had, meningioma.

As well as restricting the use of the high-dose medicines, the CHMP recommended that patients should be monitored for symptoms of meningioma, which can include change in vision, hearing loss or ringing in the ears, loss of smell, headaches, memory loss, seizures and weakness in arms or legs. If a patient is diagnosed with meningioma, treatment with these medicines must be permanently stopped. 

The product information for the high-dose medicines will also be updated to include meningioma as a rare side effect.

The recommendations follow a review by the PRAC of available data, including post-marketing safety data and results from two recent epidemiological studies.1,2 These data showed that the risk of meningioma increases with increasing dose and duration of treatment. The CHMP endorsed the PRAC’s assessment of this risk.

The CHMP opinion was sent to the European Commission, which issued legally binding decisions valid across the EU between 28 October and 28 November 2022.

1 Nguyen P, Hoisnard L, Neumann A, Zureik M, Weill A. Utilisation prolongée de l’acétate de chlormadinone et risque de méningiome intracrânien: une étude de cohorte à partir des données du SND. EPI-PHARE, 2021.

2 Nguyen P, Hoisnard L, Neumann A, Zureik M, Weill A. Utilisation prolongée de l’acétate de nomégestrol et risque de méningiome intracrânien: une étude de cohorte à partir des données du SNDS. EPI-PHARE, 2021.    

Key facts

About this medicine
Approved name
Nomegestrol and chlormadinone
International non-proprietary name (INN) or common name
  • nomegestrol
  • chlormadinone
Associated names
Zoely
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-31/1510
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.

Authorisation model
Centrally and nationally authorised products (mixed)
Decision making model
PRAC-CHMP-EC
Key dates and outcomes
Procedure start date
30/09/2021
PRAC recommendation date
07/07/2022
CHMP opinion/CMDh position date
01/09/2022
EC decision date
28/11/2022
Outcome
Risk minimisation measures

All documents

Procedure started

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Opinion provided by Committee for Medicinal Products for Human Use

  • List item

    New measures to minimise risk of meningioma with medicines containing nomegestrol or chlormadinone (PDF/117.04 KB)


    First published: 02/09/2022
    Last updated: 14/12/2022
    EMA/684243/2022

  • European Commission final decision

  • List item

    Nomegestrol and chlormadinone Article-31 referral - Annex IV (PDF/57.7 KB)


    First published: 14/12/2022

  • List item

    Nomegestrol and chlormadinone Article-31 referral - Annex III (PDF/138.75 KB)


    First published: 14/12/2022

  • List item

    Nomegestrol and chlormadinone Article-31 referral - Annex II (PDF/81.65 KB)


    First published: 14/12/2022

  • List item

    Nomegestrol and chlormadinone Article-31 referral - Annex I (PDF/134.01 KB)


    First published: 14/12/2022

  • List item

    Nomegestrol and chlormadinone Article-31 referral - Assessment report (PDF/656.76 KB)


    First published: 14/12/2022
    EMA/773938/2022

  • List item

    Nomegestrol and chlormadinone Article-31 referral - Divergent positions to CHMP opinion (PDF/74.71 KB)


    First published: 08/11/2022

  • 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.

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