We hardly knew ya! Prexige (lumaricoxib) has only been out for about a year here in Canada and it's already being tossed into the ever more crowded cox-2 scrap heap. Vioxx, Bextra and the stillborn Arcoxia have already been given the heave-ho, Prexige joins the bunch and Mobicox (meloxicam) seems to have decided that they weren't really a cox-2 after all. Do you think Celebrex is feeling a little insecure?
Actually, I think it may well be the regulatory bodies that are feeling it a bit. The basis of the last decision, by Health Canada regarding Prexige, was the higher than normal incidence of severe liver toxicity. This was precipitated by the Australian withdrawal, based on eight severe cases of toxicity, including death. In that country, lumaricoxib was available in 200 and 400 mg doses, and it was hoped that the lower Canadian doses of 100mg might have spared us the same outcome. In the Health Canada advisory we are told that they have uncovered four cases of severe toxicity at the 100 mg dose, two in Canada and two elsewhere, and based on these four cases, they felt that the security of the drug could not be guaranteed. So long Prexige.
I'm not one to argue with the experts, but haven't we seen liver toxicity with NSAID use before? In fact, one researcher, Dr Aithal, from across the pond, seems to have built his career around the toxicity of diclofenac (voltaren). He uses diclofenac as a kind of model for liver toxicity, and when your drug is being used as a model for toxicity, that can't be good. He has produced a nice review in FREE full text on NSAID liver toxicity and states that voltaren as well as sulindac have higher than usual incidences. As well,a single Scandinavian study (free full text) documented 28 cases of NSAID related liver toxicity, 10 of which lead to death. Both diclofenac and naproxen contributed 4 patients each.
I don't pretend to know whether prexige is more or less toxic than voltaren, but the evidence provided by Health Canada does seem a little thin; four cases, and doesn't take into consideration any possible reduction in mortality that cox-2's might provide. I think the bar is now raised to the point where no new NSAIDs have a chance to break into the market and the older ones are trembling in their boots. I see only naproxen in a future that looks a lot like 1975.