Europe restricts, bans Cox-2 drugs

The European Medicines Agency (EMEA), the regulatory body responsible for drug regulation in all European Union countries (a role similar to that of the FDA in the United States), has announced a number of regulatory actions for the COX-2 inhibitor class of medicines following discussions at the 14-17 February 2005 meeting of the Committee for Medicinal Products for Human Use (CHMP). This news comes at the same time that Merck intends to start selling Vioxx again. (Related article: Merck, Pfizer ignored drug safety; focused on profits alone)

The CHMP concluded that the available data show an increased risk of cardiovascular adverse events for COX-2 inhibitors as a class. The data also suggest an association between duration and dose of intake and the probability of suffering a cardiovascular event. These findings are very similar to those of the Therapeutic Goods Administration (TGA) in Australia that has also banned/limited prescription of Cox-2 drugs. This class of drugs includes Vioxx, Celebrex, Bextra, Arcoxia, Prexige, and variations of their brand names all over the globe. (Related article: Celebrex and Bextra have same risks as Vioxx, argues Merck)

The following urgent safety restrictions have been taken for COX-2 inhibitors available in the European Union:

1. A contra-indication (meaning that the drug should not be taken) is introduced for all COX-2 inhibitors in patients with ischaemic heart disease (not enough blood to the heart) or stroke.
2. As a further measure, a contra-indication is introduced for etoricoxib (Arcoxia) in patients with hypertension (high blood pressure) whose blood pressure is not under control.
3. A warning is introduced for prescribers to exercise caution when prescribing COX-2 inhibitors for patients with risk factors for heart disease, such as hypertension, hyperlipidaemia (high cholesterol levels), diabetes and smoking, as well as for patients with peripheral arterial disease.

Given the association between cardiovascular risk and exposure to COX-2 inhibitors, doctors are advised to use the lowest effective dose for the shortest possible duration of treatment
These are interim measures pending the finalization of the class review, expected in April 2005.

The Committee also concluded that more research is needed in the field to evaluate the cardiovascular safety of COX-2 inhibitors, and that ongoing cardiovascular trials should continue as planned. Companies like Merck, Pfizer, and Novartis had provided EMEA with information on their drugs. All drugmakers of Cox-2 inhibitor drugs have argued that their drugs are safe. They have made similar arguments to the ongoing FDA advisory committee meeting in the United States. (Related article: Pfizer claims Celebrex, Bextra safe drugs)

It is important to understand the position of Pfizer which has argued that there is no class effect, or in other words, Celebrex and Bextra are different from Vioxx despite having the same working mechanism. Merck, on the other hand, is arguing that if there is a problem with Vioxx, then it must be extended to other Cox-2 drugs like Celebrx and Bextra. It is very likely that Merck may be putting this argument forward merely for competitive reasons. (Related article: Merck and Pfizer fought Coke-Pepsi style marketing battle over Vioxx, Celebrex, and Bextra)

The review of COX-2 inhibitors by the European Medicines Agency began in October 2004 at the request of the European Commission. Hearings were held with the Marketing Authorisation Holders on 18 January and 15 February 2005. The whole process is not complete yet and these are merely interim decisions. The FDA will conclude its meeting today and then decide its course of action within a few weeks. (Related article: FDA tries to protect Merck and Pfizer)

This decision by EMEA stops short of banning the whole class of Cox-2 drugs. While both Celebrex and Bextra will continue to be sold in Europe, their prescriptions will be highly limited. But EMEA has specifically banned the use of Arcoxia among patients with high blood pressure.

The decision by EMEA is based on the same argument that world-famous FDA scientist Dr. David Graham has made. His research has shown that there is a class effect and there is simply no need for Cox-2 drugs on the market. (Related article: Dr. David Graham blasts Merck, Pfizer, FDA, and Cox-2 drugs)

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