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).
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).
|Approved name||Yaz 24+4|
|International non-proprietary name (INN) or common name|
ethinylestradiol / drospirenone
|Associated names||Ethinylestradiol-Drospirenone 24+4|
|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 is no longer applicable and has been replaced by Article 13 referrals.
|Status||European Commission final decision|
- Questions and answers (Q&A) - easy-to-understand summary of key issues and Committee conclusions
- Summary of Opinion - contains the CHMP opinion of the referred medicine(s)
- List of the medicines affected by the referral (Annex I)
- Scientific conclusions of the Committee (Annex II)
The following two documents are sometimes available:
- Changes to the summary of product characteristics, labeling or package leaflet (also known as Annex III) - available when changes have been recommended by the Committee
- Conditions of the marketing authorisation (also known as Annex IV) - available when the Committee recommends measures to be taken for the marketing authorisation(s) such as safety measures or extra studies