Lumiracoxib

drugbox
IUPAC_name = {2- [(2-chloro-6-fluorophenyl)amino] -5-methylphenyl}
acetic acid

---

width = 180px
CAS_number =
ATC_prefix = M01
ATC_suffix = AH06
PubChem = 151166
DrugBank =
C = 15 |H = 13 |Cl = 1 |F = 1 |N = 1 |O = 2
molecular_weight = 293.72 g/mol
bioavailability = 74% (oral)
protein_bound = >98%
metabolism = Hepatic oxidation and hydroxylation (CYP2C9)
elimination_half-life = 4 hours
excretion = Renal and fecal
pregnancy_AU = C
legal_status = ℞-only Withdrawn (Australia, New Zealand, Canada, UK, Germany, Austria, Belgium, Cyprus, Brazil)
routes_of_administration = Oral

Lumiracoxib (rINN) is a COX-2 selective inhibitor non-steroidal anti-inflammatory drug, manufactured by Novartis and still sold in few countries, including Mexico, Colombia, and the Dominican Republic, under the trade name Prexige (sometimes misquoted as "Prestige" by the media).

Lumiracoxib has several distinctive features. Its structure is different from that of other COX-2 inhibitors, such as celecoxib: lumiracoxib is an analogue 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 class of NSAIDs; it binds to a different site on the COX-2 receptor than do other COX-2 inhibitors; it is the only acidic coxib; and has the highest COX-2 selectivity of any NSAID.cite journal |author=Tacconelli S, Capone ML, Patrignani P |title=Clinical pharmacology of novel selective COX-2 inhibitors |journal=Curr Pharm Des |volume=10 |issue=6 |pages=589–601 |year=2004 |pmid=14965322 |doi= |url=http://www.bentham-direct.org/pages/content.php?CPD/2004/00000010/00000006/0003B.SGM]

Since its original approval, lumiracoxib has been withdrawn from the market in several countries, mostly due to hepatotoxicity concerns. It has never been approved for use in the United States.

History

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. However, in August 2007, Prexige was withdrawn from the market in Australia following 8 serious liver adverse events, including 2 deaths and 2 liver transplants. [ [http://www.tga.gov.au/recalls/2007/lumiracoxib.htm Urgent medicine recall - Lumiracoxib (PREXIGE) ] ] On September 27, 2007, the US Food and Drug Administration issued a not approvable letter for lumiracoxib, requiring additional safety data. [http://hugin.info/134323/R/1156327/223186.pdf] Canada withdrew Prexige (approved at 100mg dose only) in October 2007. [ [http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2007/2007_141-eng.php Withdrawal of Market Authorization for Prexige ] ] Several European Union countries followed suit in November 2007. [ [http://www.novartis.com/newsroom/media-releases/en/2007/1169462.shtml Media releases ] ]

The FDA rejected Prexige as a trade name for lumiracoxib in 2003. Prexede was suggested as an alternative, but the FDA Division of Medication Errors and Technical Support (DMETS) subsequently recommended against it as well. [http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4090B1_33_GG-FDA-Tab-U.pdf]

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. [ [http://www.tga.gov.au/media/2007/070811-lumiracoxib.htm Medicines Regulator cancels registration of anti inflammatory drug, Lumiracoxib] , "Therapeutic Goods Administration", 2007-08-11. Retrieved on 2007-08-11]

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. [http://www.tga.gov.au/media/2007/070811-lumiracoxib.htm] [http://www.tga.gov.au/recalls/2007/lumiracoxib.htm ]

New Zealand has followed suit with Australia in recalling Prexige. [ [http://www.nzherald.co.nz/category/story.cfm?c_id=278&objectid=10459030 NZ regulators ban arthritis drug - 21 Aug 2007 - Pharmaceuticals news - NZ Herald ] ]

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. [http://www.novartis.ca/downloads/en/letters/prexige_fact_20071003_e.pdf] On December 13, 2007, the European Medicines Agency recommended the withdrawal for Prexige from all EU markets. [ [http://www.emea.europa.eu/pdfs/human/press/pr/PR_Lumiracoxib_57930107en.pdf Press release: European Medicines Agency recommends withdrawal of the marketing authorisations for lumiracoxib-containing medicines, 13 December 2007] ]

On January 17, 2008, the Philippines Department of Health ordered Novartis Healthcare Phils. Inc. (Novartis) to remove (recall) all lumiracoxib from local drug stores in 2 weeks due to the harmful effects of the drug (potential serious liver-related side effects, hepatotoxicity or malfunction of the lungs). [ [http://www.abs-cbnnews.com/storypage.aspx?StoryId=105842 Abs-Cbn Interactive, DOH recalls lumiracoxib, sets two-week deadline] ]

On July 22, 2008, The Brazilian National Health Surveillance Agency ordered the withdrawal of 100 mg formulations of lumiracoxib and suspended marketing of the 400 mg formulation for 90 days, [cite news |url=http://www1.folha.uol.com.br/folha/cotidiano/ult95u425127.shtml |title=Anvisa cancela registro do Prexige; consumidor deve substituir medicamento |date=July 22, 2008 |accessdate=2008-07-22 |work=Folha de S. Paulo |language=Portuguese] after a three-year safety review found a marked increase in adverse event reports; 35% of lumiracoxib-associated adverse events reported worldwide between July 2005 and April 2008 were found to have occurred in Brazil. [cite press release |url=http://www.anvisa.gov.br/divulga/noticias/2008/220708_1.htm |title=Anvisa cancela registro do antiinflamatório Prexige |date=July 22, 2008 |accessdate=2008-07-22 |publisher=Anvisa |language=Portuguese] Lumiracoxib was definitively withdrawn from the Brazilian market on October 3, 2008. [cite news |url=http://noticias.terra.com.br/brasil/interna/0,,OI3230378-EI715,00-Anvisa+suspende+venda+e+uso+de+antiinflamatorios.html |title=Anvisa suspende venda e uso de 2 antiinflamatórios |date=October 3, 2008 |accessdate=2008-10-03 |publisher=Terra |language=Portuguese]

References

External links

* [http://arthritis.about.com/od/prexige/ About.com]
* [http://www.drugdevelopment-technology.com/projects/prexige/ Prexige]
* [http://www.forbes.com/2002/04/19/0419nvs.html Forbes]
* [http://www.pharma.us.novartis.com/newsroom/pressReleases/releaseDetail.jsp?PRID=1003&usertrack.filter_applied=true&NovaId=1178761730655802584 FDA request more information September 23, 2003]
* [http://www.npsradar.org.au/site.php?page=1&content=/npsradar/content/lumiracoxib.html NPS RADAR]
* [http://www.fda.gov/ohrms/dockets/AC/05/briefing/2005-4090B2_02_Novartis-Lumiracoxib.pdf FDA - Background Document for Lumiracoxib 1/13/2005]
*http://www.nzherald.co.nz/category/story.cfm?c_id=278&objectid=10459030