Following discussions with the European Medicines Agency ( EMEA ), Pfizer has agreed to the suspension of use of anti-inflammatory drug, Bextra ( Valdecoxib), in Europe as an interim measure pending finalisation of the assessment of COX-2 inhibitors.

Pfizer has agreed to similar actions in the United States at the request of the Food and Drug Administration.

The European Medicines Agency has an ongoing safety review of the COX-2 class of medicines.

Contraindications and warnings concerning the cardiovascular safety of all COX-2 medicines were introduced in the information for prescribers and patients in February 2005.

The Agency had previously issued a statement on 15 December 2004 concerning safety issues for patients undergoing coronary artery bypass graft ( CABG ) surgery and serious skin reactions relating to the use of two COX-2 medicines, including Bextra.

Contraindications for patients undergoing CABG surgery and additional information and warnings on the occurrence of serious skin reactions were introduced.

Until the completion of the ongoing review, prescribers are advised to monitor carefully patients being treated with Bextra and not to initiate treatment of new patients.

Two clinical studies were conducted to evaluate the safety of Valdecoxib and Parecoxib sodium ( Dynastat ), in patients following CABG surgery and another study in patients following general surgery.

The first CABG study evaluated the safety of Parecoxib sodium/Valdecoxib 40 mg BID given for up to 14 days in 462 patients ( 311 on Parecoxib sodium/Valdecoxib and 151 on placebo ).

The second CABG surgery study evaluated Parecoxib sodium ( 40mg then 20mg bid ) /Valdecoxib 20 mg bid or placebo/Valdecoxib 20 mg bid or placebo/placebo for up to 10 days in 1671 patients ( 544 receiving Parecoxib/Valdecoxib, 544 placebo/Valdecoxib and 548 placebo/placebo ).

Both CABG studies showed a higher rate of serious cardiovascular thromboembolic events ( e.g. myocardial infarction, cerebrovascular accident ) in the Parecoxib sodium/Valdecoxib treatment arm compared to the group of patients receiving placebo. This was not observed in a general surgery setting.

The EMEA has received post-marketing reports of serious skin reactions, some with fatal outcome, including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis in patients receiving Valdecoxib.
Erythema multiforme has been reported in association with the use of Parecoxib sodium.

The reported rate of these reactions appears to be greater for Valdecoxib as compared with other COX-2 selective inhibitors.

Patients appear to be at highest risk for these events early in the course of therapy, the onset of the event occurring in the majority of cases within the first two weeks of treatment.
Patients without a history of sulphonamide allergy may also be at risk for serious skin reactions.

Source: EMEA, 2005


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