Lumiracoxib

Lumiracoxib (rINN) is a COX-2 selective inhibitor non-steroidal anti-inflammatory drug, manufactured by Novartis and still sold in few countries, including Mexico, South Africa, and Brazil, under the trade name Prexige (sometimes misquoted as "Prestige" by the media). The TARGET study (Therapeutic Arthritis Research and Gastrointestinal Event Trial) was conducted with more than 18,000 patients to test its gastrointestinal and cardiovascular safety against Naproxen and Ibuprofen and also study its efficacy against these two NSAIDs.

In November 2006, Prexige received marketing approval for all European Union countries through a common procedure called MRP. As of 2007, the Food and Drug Administration (FDA) has not yet granted approval for its sale in the United States.

Lumiracoxib has a different structure from the standard COX-2 inhibitors (e.g. celecoxib). It more closely resembles the structure of diclofenac (one chlorine substituted by fluorine, the phenylacetic acid has another methyl group in meta position), making it a member of the arylalkanoic acid family of NSAIDs. It binds to a different site on the COX-2 receptor than the standard COX-2 inhibitors. It displays extremely high COX-2 selectivity.

The FDA rejected Prexige as a trade name for lumiracoxib in 2003. The FDA Division of Medication Errors and Technical Support (DMETS) subsequently recommended against the alternative name Prexede. The planned trade name for lumiracoxib in the US has not been disclosed to the public.

On September 27, 2007, the US Food and Drug Administration issued a not approvable letter for lumiracoxib, requiring additional safety data.

Withdrawal from market
On August 11, 2007, Australia's Therapeutic Goods Administration (TGA, the Australian equivalent of the FDA) cancelled the registration of lumiracoxib in Australia due to concerns that it may cause liver failure.

According to the TGA's Principal Medical Adviser, Dr Rohan Hammett, as of 10 August 2007 the TGA had received 8 reports of serious adverse liver reactions to the drug, including two deaths and two liver transplants.

"The TGA and its expert advisory committee, the Adverse Drug Reactions Advisory Committee (ADRAC), have urgently investigated these reports. ADRAC has today recommended the cancellation of the registration of Lumiracoxib due to the severity of the reported side effects associated with this drug," Dr Hammett said.

"The TGA has taken this advice to cancel the registration of Lumiracoxib in order to prevent further cases of severe liver damage.

"It seems that the longer people are on the medicine, the greater the chance of liver injury. The TGA is, therefore, advising people to stop taking the Lumiracoxib immediately and to discuss alternative treatments with their doctor," Dr Hammett said.

New Zealand has followed suit with Australia in recalling Prexige.

On October 3, 2007, Health Canada requested sales of Prexige to stop. Novartis has agreed to the request and has taken steps to do so. On December 13, 2007, the European Medicines Agency recommended the withdrawal for Prexige from all EU markets.