Cyproterone- and ethinylestradiol-containing medicines

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

Overview


Benefits of Diane 35 and its generics outweigh risks in certain patient groups

On 29 May 2013, the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) endorsed by majority (26:1) the recommendation of the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC), which concluded that the benefits of Diane 35 (cyproterone acetate 2 mg / ethinylestradiol 35 micrograms) and its generics outweigh the risks, provided that several measures are taken to minimise the risk of thromboembolism (formation of blood clots in blood vessels). These medicines should be used solely in the treatment of moderate to severe acne related to androgen sensitivity or hirsutism (excessive unwanted growth of hair in women) in women of reproductive age. Furthermore, Diane 35 and generics should only be used for the treatment of acne when alternative treatments, such as topical therapy and antibiotic treatment, have failed.

Since Diane 35 and its generics act as hormonal contraceptives, women should not take these medicines in combination with other hormonal contraceptives. Concomitant use of Diane 35 and its generics with another hormonal contraceptive will expose women to a higher dose of oestrogen and increase the risk of thromboembolism.

The risk of thromboembolism occurring with these medicines is low and well known. However, to minimise this risk, further measures should be implemented in addition to the updated product information. These include providing educational materials to prescribers and patients highlighting the risks of thromboembolism, for example a prescriber checklist to ensure that the risks, together with the signs and symptoms, are discussed with the patient.

These recommendations were endorsed by the CMDh, a body representing European Union (EU) Member States. Because the CMDh took this position by majority it was sent to the European Commission, which endorsed it and adopted a final legally binding decision on 25 July 2013.

The review of Diane 35 and its generics was triggered by the French medicines agency, the National Agency for the Safety of Medicine and Health Products (ANSM), following its decision to suspend Diane 35 and its generics in France within three months. The French decision followed a national review of the medicine by ANSM. This review highlighted serious thromboembolic events and extensive off-label use of these medicines as a contraceptive only.

Despite the PRAC recommendation ANSM proceeded with the suspension of the marketing authorisation of these medicines in France. However, the subsequent European Commission decision to maintain the marketing authorisation with the agreed risk-minimisation measures, including changes to the information to prescribers and patients, is to be implemented in all EU Member States

Key facts

About this medicine
Approved name
Cyproterone- and ethinylestradiol-containing medicines
International non-proprietary name (INN) or common name
cyproterone / ethinylestradiol
Associated names
  • Acnemine
  • Acneson
  • Chloe
  • Clairette
  • Cyprest
  • Cyprodiol
  • Diane 35
  • Dianette
  • Feminil
  • Minerva
  • Zyrona
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-107i/1357
Type
Article 107i procedures

This type of procedure is triggered when a Member State or the European Commission consider that urgent action is necessary because of a safety issue. Situations that fall under this procedure include consideration for suspension or revocation of the marketing authorisation for a medicine, the prohibition of supply of a medicine or major changes to the marketing authorisation such as deletion of indications, reduction of the recommended dose or new contraindications. The procedure is also applicable in case of a safety issue with a class of medicines.

Decision making model
PRAC-CMDh
Authorisation model
Nationally authorised product(s)
Key dates and outcomes
Procedure start date
07/02/2013
PRAC recommendation date
16/05/2013
CHMP opinion/CMDh position date
29/05/2013
EC decision date
25/07/2013
Outcome
Risk minimisation measures

Data submission

The Agency invites all stakeholders (e.g. healthcare professionals, patients' organisations, the general public) to submit data relevant to this procedure. This is in accordance with Article 107j(1) of Directive 2001/83/EC.

The following requirements apply for data to be considered:

Submitting data

Send the completed form electronically to the stakeholders' submission inbox (public@ema.europa.eu). Specify the name of the medicine in the subject line of the e-mail.

The size of the submission file should not exceed 25 MB. If your attempt to send your data package to the dedicated e-mail address is unsuccessful, please use alternative submission means.

It is of the utmost importance that data are provided promptly, to avoid undermining the safety review. Due to the urgent nature of the procedure, you are strongly advised to submit your data in English.

Protection of personal data

Personal data submitted are subject to data-protection rules as established by Regulation (EC) 45/2001. They will be treated in accordance with the specific privacy statement for public consultations (EMA/310325/2012).

Treatment and publication of data

Data submitted will be received and recorded by the Agency.

The Agency will prepare a list of all submissions received, which will be published as an annex to the PRAC assessment report for transparency purposes and public awareness.

Please note that all data submitted in the context of this procedure may be shared and disclosed in the public domain.

All documents

Procedure started

  • List item

    Cryopterone / ethinylestradiol-containing medicines: Article-107i procedure - Rationale for the triggering of procedure under Article 107i of Directive 2001/83/EC on cyproterone / ethinylestradiol (2 mg / 0.035 mg) prese... (PDF/321.36 KB)


    First published: 27/02/2013
    Last updated: 18/03/2013
    EMEA/H/A-107i/1357

  • List item

    Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Annex I (PDF/258.79 KB)

    Adopted

    First published: 11/02/2013
    Last updated: 11/02/2013
    EMA/84655/2013

  • List item

    Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Stakeholder's submission form (PDF/128.28 KB)

    Adopted

    First published: 11/02/2013
    Last updated: 11/02/2013
    EMA/639499/2012

  • List item

    Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Timetable for the procedure (PDF/88.21 KB)

    Adopted

    First published: 11/02/2013
    Last updated: 15/03/2013
    EMA/PRAC/69142/2013 Rev.1

  • List item

    Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - PRAC list of questions to be addressed by stakeholders (PDF/61.03 KB)

    Adopted

    First published: 11/02/2013
    Last updated: 11/02/2013
    EMA/PRAC/78185/2013

  • List item

    Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - PRAC list of questions (PDF/82.66 KB)

    Adopted

    First published: 11/02/2013
    Last updated: 11/02/2013
    EMA/PRAC/69149/2013

  • List item

    Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Notification (PDF/124.18 KB)


    First published: 08/02/2013
    Last updated: 08/02/2013

  • List item

    Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Start of review of Diane 35 and other medicines containing cyproterone acetate 2 mg and ethinylestradiol 35 micrograms (PDF/74.74 KB)

    Adopted

    First published: 08/02/2013
    Last updated: 08/02/2013
    EMA/76602/2013

  • Recommendation provided by Pharmacovigilance Risk Assessment Committee

    Position provided by CMDh

  • List item

    Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Divergent positions to CMDh position (PDF/25.49 KB)


    First published: 13/06/2013
    Last updated: 13/06/2013

  • List item

    Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Annex IV (PDF/29.27 KB)


    First published: 10/06/2013
    Last updated: 10/06/2013

  • List item

    Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Annex III (PDF/125.87 KB)


    First published: 10/06/2013
    Last updated: 10/06/2013

  • List item

    Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Annex I (PDF/297.73 KB)


    First published: 10/06/2013
    Last updated: 10/06/2013

  • List item

    Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Annex II (PDF/227.09 KB)


    First published: 10/06/2013
    Last updated: 10/06/2013

  • List item

    Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Benefits of Diane 35 and its generics outweigh risks in certain patient groups - PRAC recommendation endorsed by CMDh (PDF/128.79 KB)


    First published: 30/05/2013
    Last updated: 30/05/2013
    EMA/318380/2013

  • European Commission final decision

  • List item

    Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Benefits of Diane 35 and its generics outweigh risks in certain patient groups (PDF/90.39 KB)


    First published: 05/08/2013
    Last updated: 05/08/2013
    EMA/318380/2013

  • List item

    Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Benefits of Diane 35 and its generics outweigh risks in certain patient groups (PDF/90.39 KB)


    First published: 05/08/2013
    Last updated: 05/08/2013
    EMA/318380/2013

  • 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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