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Thromb Haemost 2006; 96(04): 423-432
DOI: 10.1160/TH06-08-0462
Theme Issue Article
Schattauer GmbH

Selective COX-2 inhibitors and risk of thromboembolic events – regulatory aspects

Hans-Karl Heim
1   Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Germany
,
Karl Broich
1   Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Germany
› Author Affiliations
Further Information

Publication History

Received 24 August 2006

Accepted after revision 06 September 2006

Publication Date:
29 November 2017 (online)

Also available at
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Summary

In the 1990s, the pharmaceutical industry developed selective COX-2 inhibitors (coxibs) as alternatives to conventional nonsteroidal anti-inflammatory drugs (NSAIDs), with the expectation of similar analgetic and anti-inflammatory efficacy but a reduced risk of adverse gastrointestinal (GI) effects. Marketing authorisation (MA) was granted for rofecoxib and celecoxib as first representatives of this new pharmacological class at the end of the 1990s in the EU. In the following years MAs were granted for the ´second generation` coxibs etoricoxib, parecoxib/valdecoxib and lumiracoxib. However, data from large clinical ´outcome studies` as well as epidemiological data raised concerns about the cardiovascular (CV) safety of the coxibs. In consequence, two comprehensive review processes (referrals) were initiated by the European Medicines Agency (EMEA).As a result, in the EU the use of coxibs has been contraindicated in patients with established coronary heart disease, cerebrovascular disease and peripheral arterial disease and a number of warning statements concerning CV, GI and skin toxicity have been introduced in the coxib product informations. This article provides a description of the regulatory actions taken and discusses some specific aspects of the past and future regulatory assessment of coxibs.

Keywords

Cyclooxygenase 2 inhibitors - anti-inflammatory agents - non-steroidal - cardiovascular diseases - gastrointestinal diseases - legislation - drug
 

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