Lumiracoxib

Lumiracoxib
Clinical data
Trade names Prexige
AHFS/Drugs.com International Drug Names
Pregnancy
category
  • AU: C
    Routes of
    administration
    Oral
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability 74-90%[1]
    Protein binding >98%[1]
    Metabolism Predominantly in the liver via oxidation and hydroxylation (CYP2C9)[1]
    Elimination half-life 5-8 hours[1]
    Excretion Urine (54%) and faeces (43%)[1]
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    PDB ligand
    Chemical and physical data
    Formula C15H13ClFNO2
    Molar mass 293,72 g/mol
    3D model (JSmol)
     NY (what is this?)  (verify)

    Lumiracoxib (rINN) is a carboxylic acid COX-2 selective inhibitor nonsteroidal anti-inflammatory drug, manufactured by Novartis and still sold in few countries, including Mexico, Ecuador and the Dominican Republic, under the trade name Prexige (sometimes misquoted as "Prestige" by the media).[1]

    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 enzyme than do other COX-2 inhibitors; it is the only acidic coxib and has the highest COX-2 selectivity of any NSAID.[2]

    Since its original approval, lumiracoxib has been withdrawn from the market in several countries, mostly due to its potential for causing liver failure (sometimes requiring liver transplantation). It has never been approved for use in the United States.[1]

    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 However, in August 2007, Prexige was withdrawn from the market in Australia following 8 serious liver adverse events, including 2 deaths and 2 liver transplants.[3] On September 27, 2007, the US Food and Drug Administration issued a not approvable letter for lumiracoxib, requiring additional safety data.[4] Canada withdrew Prexige (approved at 100 mg dose only) in October 2007.[5] Several European Union countries followed suit in November 2007.[6]

    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.[7]

    Withdrawal from market

    On August 11, 2007, Australia's Therapeutic Goods Administration (TGA, the national agency responsible for regulation of pharmaceuticals) cancelled the registration of lumiracoxib in Australia due to concerns that it may cause liver failure.[8]

    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.[9]

    New Zealand has followed suit with Australia in recalling Prexige.[10]

    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.[11] On December 13, 2007, the European Medicines Agency recommended the withdrawal for Prexige from all EU markets.[12]

    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).[13]

    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,[14] 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.[15] Lumiracoxib was definitively withdrawn from the Brazilian market on October 3, 2008.[16]

    On November 12, 2008, INVIMA, the Colombian National Institute for Food and Drug Surveillance ordered the withdrawal of all presentations of lumiracoxib (Prexige), due to the international reports on hepatotoxicity.

    References

    1. 1 2 3 4 5 6 7 Shi, S; Klotz, U (March 2008). "Clinical use and pharmacological properties of selective COX-2 inhibitors". European Journal of Clinical Pharmacology. 64 (3): 233–52. doi:10.1007/s00228-007-0400-7. PMID 17999057.
    2. Tacconelli S, Capone ML, Patrignani P (2004). "Clinical pharmacology of novel selective COX-2 inhibitors". Curr Pharm Des. 10 (6): 589–601. doi:10.2174/1381612043453108. PMID 14965322.
    3. Urgent medicine recall - Lumiracoxib (PREXIGE)
    4. http://hugin.info/134323/R/1156327/223186.pdf
    5. Withdrawal of Market Authorization for Prexige
    6. Media releases
    7. http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4090B1_33_GG-FDA-Tab-U.pdf
    8. Medicines Regulator cancels registration of anti inflammatory drug, Lumiracoxib Archived 2009-06-03 at the Wayback Machine., Therapeutic Goods Administration, 11 August 2007. Retrieved on 2007-08-11
    9. "Archived copy". Archived from the original on 2009-06-03. Retrieved 2007-08-10.
    10. "NZ regulators ban arthritis drug". The New Zealand Herald. 21 August 2007. Retrieved 12 September 2011.
    11. http://www.novartis.ca/downloads/en/letters/prexige_fact_20071003_e.pdf%5Bpermanent+dead+link%5D
    12. Press release: European Medicines Agency recommends withdrawal of the marketing authorisations for lumiracoxib-containing medicines, 13 December 2007 Archived 11 September 2008 at the Wayback Machine.
    13. Abs-Cbn Interactive, DOH recalls lumiracoxib, sets two-week deadline
    14. "Anvisa cancela registro do Prexige; consumidor deve substituir medicamento". Folha de S. Paulo (in Portuguese). July 22, 2008. Retrieved 2008-07-22.
    15. "Anvisa cancela registro do antiinflamatório Prexige" (Press release) (in Portuguese). Anvisa. July 22, 2008. Retrieved 2008-07-22.
    16. "Anvisa suspende venda e uso de 2 antiinflamatórios" (in Portuguese). Terra. October 3, 2008. Retrieved 2008-10-03.
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