Manufacturers of the pain killing COX-2 inhibitors, which have come under increased scrutiny in recent months [[20/12/04a]], [[20/10/04c]], [[22/10/04f]], were left reeling yesterday after the European regulatory agency, the EMEA, revealed a number of “urgent safety restrictions” for the drugs.
The Committee for Medicinal Products for Human Use, which has been has been reviewing the drugs’ safety profile after Merck & Co withdrew Vioxx (rofexocib) from the market when clinical trial data showed an increased risk of heart attack and stroke [[22/10/04f]], [[07/10/04c]], [[01/10/04a]], concluded that the increased risk of cardiovascular side effects was in fact a class effect. Pfizer in particular, which markets the COX-2s Celebrex (celecoxib) and Bextra (valdecoxib), has argued that the cardiovascular risk seen with Vioxx is specific to that drug and its mechanism of action and not to the class as a whole [[17/02/05b]].
As a result, all COX-2 inhibitors are now contra-indicated in patients with ischaemic heart disease or stroke in Europe, while Merck’s Arcoxia (etoricoxib) in particular should not be prescribed in patients with hypertension whose blood pressure is not under control. In addition, prescribers are warned to exercise caution when prescribing COX-2 inhibitors for patients with risk factors for heart disease, such as hypertension, 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, the CHMP also advises doctors to use the lowest effective dose for the shortest possible duration of treatment. The committee also concluded that more research should be conducted to evaluate the products’ CV safety profile, and that ongoing cardiovascular trials should continue as planned.
All eyes will now be keenly trained on the all-important US market, where the country’s Food and Drug Administration is currently assessing whether regulatory action is warranted [[17/02/05c]].