Ethinylestradiol-Drospirenone 24+4 - referral

Current status

European Commission final decision

Overview

On 19 April 2012, the European Medicines Agency completed an arbitration procedure for Yaz 24+4 and Ethinylestradiol-Drospirenone 24+4. The Agency's Committee for Medicinal Products for Human Use (CHMP) had been asked to consider a proposed change to the marketing authorisations for these medicines to include a new indication for the treatment of moderate acne in women seeking oral contraception. The Committee concluded that the change to the marketing authorisations cannot be granted.

What are Yaz 24+4 and Ethinylestradiol-Drospirenone 24+4?

Yaz 24+4 and Ethinylestradiol-Drospirenone 24+4 are combined contraceptive pills. They contain two active substances, ethinylestradiol and drospirenone, which are derived from natural hormones produced in the ovaries: ethinylestradiol is derived from oestrogen and drospirenone is derived from progesterone. Yaz 24+4 and Ethinylestradiol-Drospirenone 24+4 work by changing the body's hormonal balance to prevent ovulation, by altering the mucus in the cervix (neck of the womb) and by thinning the endometrium (the lining of the womb).

The company that markets Yaz 24+4 and Ethinylestradiol-Drospirenone 24+4 is Bayer B.V.

Why were Yaz 24+4 and Ethinylestradiol-Drospirenone 24+4 reviewed?

Yaz 24+4 and Ethinylestradiol-Drospirenone 24+4 are authorised in several Member States of the European Union (EU)¹ under a mutual-recognition procedure on the basis of an initial authorisation granted by the Netherlands. The company applied for a change to the marketing authorisations of these medicines to extend their use to include the 'treatment of moderate acne vulgaris only in women seeking oral contraception'. This change was to be recognised in the Netherlands and all other concerned Member States. Because the Member States were not able to reach an agreement on this new indication, on 28 and 29 June 2011 the Italian and Swedish medicines regulatory agencies referred the matter to the CHMP for arbitration.

The grounds for the referral were concerns over whether the medicines' benefits in the combined indication outweighed their risks, particularly the risk of venous thromboembolism (VTE, formation of blood clots in the veins).

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¹ Yaz is authorised in all EU Member States except Hungary, and Ethinylestradiol-Drospirenone 24+4 is authorised in the following Member States: Austria, Bulgaria, Cyprus, the Czech Republic, Denmark, Finland, France, Germany, Greece, Italy, Malta, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden and the United Kingdom.

What are the conclusions of the CHMP?

The Committee reviewed the two main studies presented by the company to support the new indication. The CHMP noted the overall effectiveness of Yaz 24+4 and Ethinylestradiol-Drospirenone 24+4 compared with placebo in the treatment of acne.

The Committee also considered the known risks with Yaz 24+4 and Ethinylestradiol-Drospirenone 24+4, including VTE. Since acne is a common problem in young women, the CHMP was concerned that the measures proposed by the company to ensure that these medicines would be used to treat acne only in women seeking oral contraception were not sufficient. Women not seeking contraception would therefore be unnecessarily exposed to the risks of Yaz 24+4 and Ethinylestradiol-Drospirenone 24+4 when alternative acne treatments are available.

Therefore, based on the evaluation of the currently available data and the scientific discussion within the Committee, the CHMP considered that the benefits of Yaz 24+4 and Ethinylestradiol-Drospirenone 24+4 did not outweigh their risks in the proposed new indication. The Committee concluded that the variation to the marketing authorisations for these medicines cannot be approved.

The European Commission issued the decisions on 3 July 2012 (Yaz 24+4) and 6 July 2012 (Ethinylestradiol-Drospirenone 24+4).

Questions and answers on Ethinylestradiol-Drospirenone 24+4 (ethinylestradiol / drospirenone, 0.02 mg/3 mg tablets)

AdoptedReference Number: EMA/257547/2012 Rev.1Summary:

On 19 April 2012, the European Medicines Agency completed an arbitration procedure for Yaz 24+4 and associated names. The Agency’s Committee for Medicinal Products for Human Use (CHMP) had been asked to consider a proposed change to the marketing authorisation for Yaz 24+4 to include a new indication for the treatment of moderate acne in women seeking oral contraception. The Committee concluded that the change to the marketing authorisation cannot be granted.

Key facts

About this medicine

• Approved name:
  Ethinylestradiol-Drospirenone 24+4
• International non-proprietary name (INN) or common name:
  • ethinyl estradiol
  • drospirenone
• Associated names:
  Yaz 24+4

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-6(12)/1313
• Type:
  Article 6(12) referrals (prior to January 2010)

  This type of referral was triggered for a medicine that had been authorised by mutual recognition or via the decentralised procedure when there was disagreement between Member States on a variation (type II). This referral has been replaced by Article 13 referrals.

Key dates and outcomes

• CHMP opinion date:
  19/04/2012
• EC decision date:
  06/07/2012

All documents

European Commission final decision

Ethinylestradiol-Drospirenone 24+4 Article-6(12) referral - Annex I

Ethinylestradiol-Drospirenone 24+4 Article-6(12) referral - Annex II

Ethinylestradiol-Drospirenone 24+4 Article-6(12) referral - Assessment report

AdoptedReference Number: EMA/399943/2012

Questions and answers on Ethinylestradiol-Drospirenone 24+4 (ethinylestradiol / drospirenone, 0.02 mg/3 mg tablets)

AdoptedReference Number: EMA/257547/2012 Rev.1Summary:

On 19 April 2012, the European Medicines Agency completed an arbitration procedure for Yaz 24+4 and associated names. The Agency’s Committee for Medicinal Products for Human Use (CHMP) had been asked to consider a proposed change to the marketing authorisation for Yaz 24+4 to include a new indication for the treatment of moderate acne in women seeking oral contraception. The Committee concluded that the change to the marketing authorisation cannot be granted.

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.