Lumiracoxib

Last updated
Lumiracoxib
Lumiracoxib.svg
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
  • {2-[(2-chloro-6-fluorophenyl)amino]-5-methylphenyl}acetic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
Chemical and physical data
Formula C15H13ClFNO2
Molar mass 293.72 g·mol−1
3D model (JSmol)
  • Clc2cccc(F)c2Nc1ccc(cc1CC(=O)O)C
  • InChI=1S/C15H13ClFNO2/c1-9-5-6-13(10(7-9)8-14(19)20)18-15-11(16)3-2-4-12(15)17/h2-7,18H,8H2,1H3,(H,19,20) Yes check.svgY
  • Key:KHPKQFYUPIUARC-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Lumiracoxib is a COX-2 selective inhibitor nonsteroidal anti-inflammatory drug.

Contents

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]

It was patented in 1997 and approved for medical use in 2003. [3] It was manufactured by Novartis and is still sold in few countries, including Mexico, Ecuador and the Dominican Republic, under the trade name Prexige. [1] Lumiracoxib has been withdrawn from the market in several countries, mostly due to its potential for causing liver failure (sometimes requiring liver transplantation).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 However, in August 2007, Prexige was withdrawn from the market in Australia following 8 serious liver adverse events, including 2 deaths and 2 liver transplants. [4] On September 27, 2007, the US Food and Drug Administration issued a not approvable letter for lumiracoxib, requiring additional safety data. [5] Canada withdrew Prexige (approved at 100 mg dose only) in October 2007. [6] Several European Union countries followed suit in November 2007. [7]

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. [8]

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. [9]

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. [10]

New Zealand has followed suit with Australia in recalling Prexige. [11]

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

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). [14]

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, [15] 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. [16] Lumiracoxib was definitively withdrawn from the Brazilian market on October 3, 2008. [17]

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.

Related Research Articles

<span class="mw-page-title-main">Nonsteroidal anti-inflammatory drug</span> Class of therapeutic drug for relieving pain and inflammation

Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of use, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.

<span class="mw-page-title-main">Cyclooxygenase</span> Class of enzymes

Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for biosynthesis of prostanoids, including thromboxane and prostaglandins such as prostacyclin, from arachidonic acid. A member of the animal-type heme peroxidase family, it is also known as prostaglandin G/H synthase. The specific reaction catalyzed is the conversion from arachidonic acid to prostaglandin H2 via a short-living prostaglandin G2 intermediate.

<span class="mw-page-title-main">Diclofenac</span> Nonsteroidal anti-inflammatory drug

Diclofenac, sold under the brand name Voltaren among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout. It can be taken orally, inserted rectally as a suppository, injected intramuscularly, injected intravenously, applied to the skin topically, or through eye drops. Improvements in pain last up to eight hours. It is also available as the fixed-dose combination diclofenac/misoprostol (Arthrotec) to help protect the stomach.

<span class="mw-page-title-main">Naproxen</span> Nonsteroidal anti-inflammatory drug (NSAID) used to treat pain

Naproxen, sold under the brand name Aleve among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, and inflammatory diseases such as rheumatoid arthritis, gout and fever. It is taken orally. It is available in immediate and delayed release formulations. Onset of effects is within an hour and lasts for up to twelve hours. Naproxen is also available in salt form, naproxen sodium, which has better solubility when taken orally.

<span class="mw-page-title-main">Rofecoxib</span> Nonsteroidal anti-inflammatory drug

Rofecoxib is a COX-2-selective nonsteroidal anti-inflammatory drug (NSAID). It was marketed by Merck & Co. to treat osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, acute pain conditions, migraine, and dysmenorrhea. Rofecoxib was approved in the US by the US Food and Drug Administration (FDA) in May 1999, and was marketed under the brand names Vioxx, Ceoxx, and Ceeoxx. Rofecoxib was available by prescription in both tablets and as an oral suspension.

<span class="mw-page-title-main">Celecoxib</span> Nonsteroidal anti-inflammatory medication

Celecoxib, sold under the brand name Celebrex among others, is a COX-2 inhibitor and nonsteroidal anti-inflammatory drug (NSAID). It is used to treat the pain and inflammation in osteoarthritis, acute pain in adults, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, painful menstruation, and juvenile rheumatoid arthritis. It may also be used to decrease the risk of colorectal adenomas in people with familial adenomatous polyposis. It is taken by mouth. Benefits are typically seen within an hour.

Etanercept, sold under the brand name Enbrel among others, is a biologic medical product that is used to treat autoimmune diseases by interfering with tumor necrosis factor (TNF), a soluble inflammatory cytokine, by acting as a TNF inhibitor. It has US Food and Drug Administration (FDA) approval to treat rheumatoid arthritis, juvenile idiopathic arthritis and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. Tumor necrosis factor alpha (TNFα) is the "master regulator" of the inflammatory (immune) response in many organ systems. Autoimmune diseases are caused by an overactive immune response. Etanercept has the potential to treat these diseases by inhibiting TNF-alpha.

<span class="mw-page-title-main">Indometacin</span> Anti-inflammatory drug

Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. It works by inhibiting the production of prostaglandins, endogenous signaling molecules known to cause these symptoms. It does this by inhibiting cyclooxygenase, an enzyme that catalyzes the production of prostaglandins.

<span class="mw-page-title-main">Etoricoxib</span> COX-2 selective NSAID medication

Etoricoxib, sold under the brand name Arcoxia, is a selective COX-2 inhibitor developed and commercialized by Merck. It is approved in 63 countries worldwide as of 2007, except the United States where the Food and Drug Administration sent a Non Approvable Letter to Merck and required them to provide additional data.

<span class="mw-page-title-main">Piroxicam</span> Chemical compound

Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class used to relieve the symptoms of painful inflammatory conditions like arthritis. Piroxicam works by preventing the production of endogenous prostaglandins which are involved in the mediation of pain, stiffness, tenderness and swelling. The medicine is available as capsules, tablets and, in some countries, as a prescription-free gel 0.5%. It is also available in a betadex formulation, which allows a more rapid absorption of piroxicam from the digestive tract. Piroxicam is one of the few NSAIDs that can be given parenteral routes.

<span class="mw-page-title-main">Nimesulide</span> Anti-inflammatory drug

Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) with pain medication and fever reducing properties. Its approved indications are the treatment of acute pain, the symptomatic treatment of osteoarthritis, and primary dysmenorrhoea in adolescents and adults above 12 years old.

<span class="mw-page-title-main">Ketorolac</span> Nonsteroidal anti-inflammatory drug (NSAID; analgesic)

Ketorolac, sold under the brand name Toradol among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain. Specifically it is recommended for moderate to severe pain. Recommended duration of treatment is less than six days, and in Switzerland not more than seven days. It is used by mouth, by nose, by injection into a vein or muscle, and as eye drops. Effects begin within an hour and last for up to eight hours. Ketorolac also has antipyretic (fever-reducing) properties.

<span class="mw-page-title-main">Etodolac</span> Nonsteroidal anti-inflammatory drug

Etodolac is a nonsteroidal anti-inflammatory drug (NSAID).

<span class="mw-page-title-main">Nabumetone</span> NSAID analgesic and anti-inflammatory drug

Nabumetone, sold under the brand name Relafen among others, is a nonsteroidal anti-inflammatory drug (NSAID). Nabumetone was developed by Beecham and first received regulatory approval in 1991.

<span class="mw-page-title-main">Nilotinib</span> Chemical compound

Nilotinib, sold under the brand name Tasigna among others, is a anti-cancer medication used to treat chronic myelogenous leukemia (CML) which has the Philadelphia chromosome. It may be used both in initial cases of chronic phase CML as well as in accelerated and chronic phase CML that has not responded to imatinib. It is taken by mouth.

<span class="mw-page-title-main">Nepafenac</span> NSAID analgesic and anti-inflammatory drug

Nepafenac, sold under the brand name Nevanac among others, is a nonsteroidal anti-inflammatory drug (NSAID), usually sold as a prescription eye drop 0.1% solution (Nevanac) or 0.3% solution (Ilevro). It is used to treat pain and inflammation associated with cataract surgery. Nepafenac is a prodrug of amfenac, an inhibitor of COX-1 and COX-2 activity.

COX-inhibiting nitric oxide donators (CINODs), also known as NO-NSAIDs, are a new class of nonsteroidal anti-inflammatory drug (NSAID) developed with the intention of providing greater safety than existing NSAIDs.

Cyclooxygenases are enzymes that take part in a complex biosynthetic cascade that results in the conversion of polyunsaturated fatty acids to prostaglandins and thromboxane(s). Their main role is to catalyze the transformation of arachidonic acid into the intermediate prostaglandin H2, which is the precursor of a variety of prostanoids with diverse and potent biological actions. Cyclooxygenases have two main isoforms that are called COX-1 and COX-2. COX-1 is responsible for the synthesis of prostaglandin and thromboxane in many types of cells, including the gastro-intestinal tract and blood platelets. COX-2 plays a major role in prostaglandin biosynthesis in inflammatory cells and in the central nervous system. Prostaglandin synthesis in these sites is a key factor in the development of inflammation and hyperalgesia. COX-2 inhibitors have analgesic and anti-inflammatory activity by blocking the transformation of arachidonic acid into prostaglandin H2 selectively.

<span class="mw-page-title-main">Apremilast</span> Medication for psoriasis and psoriatic arthritis

Apremilast, sold under the brand name Otezla among others, is a medication for the treatment of certain types of psoriasis and psoriatic arthritis. The drug acts as a selective inhibitor of the enzyme phosphodiesterase 4 (PDE4). It is taken by mouth.

Onasemnogene abeparvovec, sold under the brand name Zolgensma, is a gene therapy used to treat spinal muscular atrophy (SMA), a disease causing muscle function loss in children. It involves a one-time infusion of the medication into a vein. It works by providing a new copy of the SMN gene that produces the SMN protein.

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. S2CID   24063728.
  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. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 518. ISBN   9783527607495.
  4. ↑ "Urgent medicine recall - Lumiracoxib (PREXIGE)". Therapeutic Goods Administration . Archived from the original on 2007-08-27. Retrieved 2007-08-11.
  5. ↑ "Prexige® receives "not approvable" letter in the US despite being one of the most studied COX-2 inhibitors" (PDF). Novartis.
  6. ↑ "Withdrawal of Market Authorization for Prexige". Health Canada. November 2021.
  7. ↑ "United Kingdom and Germany suspend marketing and sale of Prexige® pending outcome of European regulatory review". Novartis AG. Archived from the original on 2009-09-05. Retrieved 2008-07-02.
  8. ↑ "NDA 21-521/ind 58,495 Prexige (COX189, lumiracoxib 100 mgs tablets)" (PDF). Food and Drug Administration . Archived from the original (PDF) on 2017-05-04. Retrieved 2019-12-16.
  9. ↑ "Medicines Regulator cancels registration of anti inflammatory drug, Lumiracoxib". Therapeutic Goods Administration . 11 August 2007. Archived from the original on 2009-06-03. Retrieved 11 August 2007.
  10. ↑ "Media statement - Medicines Regulator cancels registration of anti inflammatory drug, Lumiracoxib (Prexige)". Therapeutic Goods Administration . Archived from the original on 2009-06-03. Retrieved 2007-08-10.
  11. ↑ "NZ regulators ban arthritis drug". The New Zealand Herald . 21 August 2007. Archived from the original on 29 September 2007. Retrieved 12 September 2011.
  12. ↑ "Important Safety Information on Prexige (lumiracoxib)" (PDF). www.novartis.ca. Archived from the original (PDF) on 9 October 2007. Retrieved 25 January 2022.
  13. ↑ "European Medicines Agency recommends withdrawal of the marketing authorisations for lumiracoxib-containing medicines" (PDF). Press release. 13 December 2007. Archived from the original (PDF) on 11 September 2008.
  14. ↑ "DOH recalls lumiracoxib, sets two-week deadline". Abs-Cbn Interactive.
  15. ↑ "Anvisa cancela registro do Prexige; consumidor deve substituir medicamento" [Anvisa cancels Prexige registration; consumer should substitute medicine]. Folha de S. Paulo (in Portuguese). July 22, 2008. Retrieved 2008-07-22.
  16. ↑ "Anvisa cancela registro do antiinflamatório Prexige" [Anvisa cancels registration of the anti-inflammatory drug Prexige] (Press release) (in Portuguese). Anvisa. July 22, 2008. Archived from the original on July 26, 2008. Retrieved 2008-07-22.
  17. ↑ "Anvisa suspende venda e uso de 2 antiinflamatórios" [Anvisa suspends sale and use of 2 anti-inflammatories] (in Portuguese). Terra. October 3, 2008. Retrieved 2008-10-03.
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