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European Commission final decision


The COX-2 inhibitors celecoxib, etoricoxib, lumiracoxib, parecoxib, rofecoxib and valdecoxib comprise a relatively new group of substances whose common pharmacological action is the selective inhibition of cyclooxygenase-2. COX-2 inhibitors have been introduced in medical practice for treatment of patients with chronic inflammatory degenerative diseases such as rheumatoid arthritis and osteoarthritis.

In September 2004, the Marketing Authorisation Holder of rofecoxib informed the EMEA that new clinical trial (APPROVe) data for rofecoxib have revealed a risk of thrombotic cardiovascular events. These data resulted in the worldwide withdrawal of rofecoxib (Vioxx) from the market on 30 September 2004 by the Marketing Authorisation Holder and raised questions regarding the cardiovascular safety of other Cox-2 inhibitors.

Further to discussions at the CHMP October 2004 plenary meeting, the European Commission recommended that this public health issue on all aspects of cardiovascular safety including thrombotic events and cardio-renal events should be the subject of Community referrals under Article 31 of Directive 2001/83/EC, as amended regarding decentrally authorised products containing celecoxib, etoricoxib and lumiracoxib and subject to a review procedure under Article 18 of Council Regulation (EEC) No 2309/93, as amended regarding the centrally authorised products containing celecoxib (Onsenal), parecoxib (Dynastat/Rayzon) and valdecoxib (Bextra/Valdyn). These review procedures were started in November 2004.

On 18 November 2004, the CHMP requested comprehensive cardiovascular safety information for these products.

On 7 April 2005, the FDA (Food and Drug Administration) and the EMEA requested Pfizer to voluntarily withdraw Bextra (valdecoxib) from the market. Pfizer agreed to suspend sale and marketing of Bextra worldwide pending further discussions on the unfavorable risk versus benefit due to data on serious skin reactions.

On 20 April 2005, Pfizer presented data on serious skin reactions for valdecoxib during a hearing.

Therefore, on 20 April 2005 further to a request from the EC, the CHMP broadened the scope of the procedure under Article 31 of Directive 2001/83/EC, as amended and the review procedure under Article 18 of Council Regulation (EEC) No 2309/93, to include the assessment of serious skin reactions in the ongoing class review in addition to the cardiovascular safety aspects.

The Marketing Authorisation Holder of etoricoxib provided written explanations by 10 January and 10 May 2005. Oral explanation was given by the Marketing Authorisation Holder on 18 January 2005.

Upon consideration of all available data, the CHMP adopted an opinion for etoricoxib on 23 June 2005 recommending the maintenance of the Marketing Authorisations for etoricoxib containing medicinal products in the indications stated in the Summary of Product Characteristics as set out in Annex III.

The list of product names concerned is given in Annex I. The scientific conclusions are provided in Annex II, together with the amended Summary of Product Characteristics in Annex III.

On the basis of the CHMP Opinion, the European Commission issued a Decision on 28 November 2005.

* Notes: The information given in this document and Annexes reflect only the CHMP Opinion dated 23 June 2005. The competent authorities of the Member States will continue to keep the product under regular review.

Key facts

Approved name
International non-proprietary name (INN) or common name
Reference number
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.

European Commission final decision
Opinion date
EC decision date

All documents

Document description

  • 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 havebeen 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

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