5.10.07

Another COX-2 inhibitor bites the dust

Health Canada has banned the sale of lumiracoxib (Prexige), an anti-inflammatory drug used to treat osteoarthritis, after determining that it poses a significant risk to the livers of those taking it. It was banned in Australia in August (2007) after being linked to serious liver damage, including full out liver failure. As the FDA has not yet granted its approval, this drug is not for sale in the US (and now probably won't ever be), and I've just lost the interest of most of my readers. Stick with me, folks, it's almost over.

Now, lumiracoxib is a selective inhibitor of COX-2. Rofecoxib (Vioxx), another COX-2 selective inhibitor, was withdrawn from the market in 2004 after being linked to an entirely different problem, an increased risk of adverse cardiovascular events (i.e. heart attack and stroke). Lumiracoxib is structurally dissimilar to your standard COX-2 inhibitors, including rofecoxib, which might explain why it causes a different problem. It is known to be metabolized by the liver, so it's possible that certain liver enzymes are capable of transforming it into an extremely reactive metabolite that, unless detoxified by other enzymes, goes on a cell killing spree. Instant hepatitis. It could be that most people possess either too little of the activating enzyme(s) or just enough of the detoxifying enzyme(s) that they are not appreciably harmed by the drug. Please note that the above was pure, slightly educated speculation. In any event, it's off the market, so Canadians are good to go.

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- Rordorf CM, Choi L, Marshall P, Mangold JB. Clinical pharmacology of lumiracoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet. 2005;44(12):1247-66. Review.
- http://en.wikipedia.org/wiki/Lumiracoxib

1 chemically inspired comments:

DrSnowboard said...

Well, different to vioxx but not tooo different to diclofenac it's ancestor - which also has a history of idiosyncratic liver toxicity ascribed to glucuronide conjugation of the hydroxylated form. OK, so the methyl is there to block the obvious site of oxidation but what if it happens on the other ring?
Cynics would also disagree with the 'selective' COX2 tag - those assays are very sensitive to how you run them and a company with an existing NSAID franchise wouldn't want to miss the new marketing boat now would they?