• Procedure started
  • Under evaluation
  • CHMP opinion
  • European Commission final decision
Current status:
European Commission final decision


The COX-2 inhibitors celecoxib, etoricoxib, rofecoxib, parecoxib 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.

Rofecoxib and celecoxib have been first authorised in the EU for these indications, and subsequently rofecoxib for treatment of acute pain and pain due to primary dysmenorrhoea. Etoricoxib received later authorisation with similar indications in some EU-member states. Valdecoxib received a positive opinion for the rheumatic indications and primary dysmenorrhoea and was authorised in March 2003.Parecoxib, a prodrug of valdecoxib, was authorised in March 2002 for short-term treatment of postsurgical pain, when used intravenously or intramuscularly. Celecoxib received an authorisation in October 2003 in an orphan drug indication (familial adenomatous polyposis).

In July 2002, France notified the EMEA and submitted grounds for the referral under Article 31 of Council Directive 2001/83/EC as amended for medicinal products containing celecoxib, etoricoxib, rofecoxib, valdecoxib and parecoxib.

The CPMP, during its meeting held from 23 to 25 July 2002 decided to start a referral procedure under Article 31 of Directive 2001/83/EC as amended, for medicinal products containing celecoxib, etoricoxib, parecoxib, rofecoxib and valdecoxib. The questions identified related to gastrointestinal and cardiovascular safety. In October 2002, the CPMP asked additional questions relating to serious hypersensitivity reactions (anaphylaxis and angioedema) and serious skin reactions including Stevens- Johnson syndrome, toxic epidermal necrolysis, erythema multiforme and exfoliative dermatitis in patients treated with COX-2 inhibitors.

The Marketing Authorisation Holders provided written explanations by 31 October 2002, and supplementary information by 30 April 2003 and by 15 August 2003. An oral explanation was given by the Marketing Authorisation Holders on 24 September 2003.

Upon consideration of all available data, the CPMP adopted an opinion on 20 November 2003, which was revised on 26 February 2004. This opinion recommended the maintenance of the Marketing Authorisations for celecoxib containing medicinal 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 CPMP Opinion, the European Commission issued a Decision on 29 April 2004.

* Notes: The information given in this document and Annexes reflect only the CPMP Opinion dated 20 November 2003. The Member States competent authorities 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 takenfor the marketing authorisation(s) such as safety measures or extra studies

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