Cyproterone- and ethinylestradiol-containing medicines
- Procedure started
- Under evaluation
- PRAC recommendation
- CMDh position
- European Commission final decision
Table of contents
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
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Approved name |
Cyproterone- and ethinylestradiol-containing medicines
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International non-proprietary name (INN) or common name |
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Associated names |
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About this procedure
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Current status |
European Commission final decision
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Reference number |
EMEA/H/A-107i/1357
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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. |
Authorisation model |
Nationally authorised product(s)
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Decision making model |
PRAC-CMDh
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Key dates and outcomes
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Procedure start date |
07/02/2013
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PRAC recommendation date |
16/05/2013
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CHMP opinion/CMDh position date |
29/05/2013
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EC decision date |
25/07/2013
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Outcome |
Risk minimisation measures
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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:
- Submissions must be accompanied by the submission form below, with all fields completed. The form must be used with Adobe Reader X+ or Adobe Acrobat X+:
Stakeholder's submission form
- Data submitted should make reference to the Pharmacovigilance Risk Assessment Committee (PRAC) questions:
PRAC list of questions to be addressed by stakeholders
- The submission of all data should take place by 11 March 2013.
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
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
Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Annex I (PDF/258.79 KB)
First published: 11/02/2013
Last updated: 11/02/2013
EMA/84655/2013
Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Stakeholder's submission form (PDF/128.28 KB)
First published: 11/02/2013
Last updated: 11/02/2013
EMA/639499/2012
Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Timetable for the procedure (PDF/88.21 KB)
First published: 11/02/2013
Last updated: 15/03/2013
EMA/PRAC/69142/2013 Rev.1
Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - PRAC list of questions to be addressed by stakeholders (PDF/61.03 KB)
First published: 11/02/2013
Last updated: 11/02/2013
EMA/PRAC/78185/2013
Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - PRAC list of questions (PDF/82.66 KB)
First published: 11/02/2013
Last updated: 11/02/2013
EMA/PRAC/69149/2013
Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Notification (PDF/124.18 KB)
First published: 08/02/2013
Last updated: 08/02/2013
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)
First published: 08/02/2013
Last updated: 08/02/2013
EMA/76602/2013
Recommendation provided by Pharmacovigilance Risk Assessment Committee
Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - PRAC assessment report (PDF/592.72 KB)
First published: 10/06/2013
Last updated: 13/06/2013
EMA/339116/2013
Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - PRAC recommendations on Diane 35: Questions and answers (PDF/72.48 KB)
First published: 17/05/2013
Last updated: 17/05/2013
EMA/280182/2013
Position provided by CMDh
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
Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Annex IV (PDF/29.27 KB)
First published: 10/06/2013
Last updated: 10/06/2013
Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Annex III (PDF/125.87 KB)
First published: 10/06/2013
Last updated: 10/06/2013
Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Annex I (PDF/297.73 KB)
First published: 10/06/2013
Last updated: 10/06/2013
Cyproterone / ethinylestradiol-containing medicines: Article-107i procedure - Annex II (PDF/227.09 KB)
First published: 10/06/2013
Last updated: 10/06/2013
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
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.