Piroxicam

Piroxicam
Clinical data
Pronunciation	/paɪˈrɒksɪˌkæm/
Trade names	Feldene, others
Other names	Piroksikam, piroxikam
AHFS/Drugs.com	Monograph
MedlinePlus	a684045
Pregnancy; category	AU: C; ;
Routes of; administration	By mouth
ATC code	M01AC01 (WHO) M02AA07 (WHO), S01BC06 (WHO);
Legal status
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: WARNINGRx-only; EU: Rx-only;
Pharmacokinetic data
Protein binding	99%
Metabolism	Liver-mediated hydroxylation and glucuronidation
Elimination half-life	50 hours
Excretion	Urine, faeces
Identifiers
	IUPAC name 4-Hydroxy-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide;
CAS Number	36322-90-4 ;
PubChem CID	54676228;
IUPHAR/BPS	7273;
DrugBank	DB00554 ;
ChemSpider	10442653 ;
UNII	13T4O6VMAM;
KEGG	D00127 ;
ChEBI	CHEBI:8249 ;
ChEMBL	ChEMBL527 ;
CompTox Dashboard (EPA)	DTXSID5021170 ;
ECHA InfoCard	100.048.144
Chemical and physical data
Formula	C15H13N3O4S
Molar mass	331.35 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES OC=2c1ccccc1S(=O)(=O)N(C)C=2C(=O)Nc3ccccn3;
	InChI InChI=1S/C15H13N3O4S/c1-18-13(15(20)17-12-8-4-5-9-16-12)14(19)10-6-2-3-7-11(10)23(18,21)22/h2-9,19H,1H3,(H,16,17,20) ; Key:QYSPLQLAKJAUJT-UHFFFAOYSA-N ;
	(verify)

Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class used to relieve the symptoms of painful inflammatory conditions like arthritis.^[4]^[5] Piroxicam works by preventing the production of endogenous prostaglandins which are involved in the mediation of pain, stiffness, tenderness and swelling.^[4] The medicine is available as capsules, tablets and, in some countries, as a prescription-free gel 0.5%.^[6] It is also available in a betadex formulation, which allows a more rapid absorption of piroxicam from the digestive tract.^[4] Piroxicam is one of the few NSAIDs that can be given parenteral routes.^{[citation needed]}

It was patented in 1968 by Pfizer and approved for medical use in 1979.^[7] It became generic in 1992,^[8] and is marketed worldwide under many brandnames.^[1]

Medical uses

It is used in the treatment of certain inflammatory conditions like rheumatoid and osteoarthritis, primary dysmenorrhoea, and postoperative pain; it acts as an analgesic, especially where there is an inflammatory component.^[4] The European Medicines Agency issued a review of its use in 2007 and recommended that its use be limited to the treatment of chronic inflammatory conditions, as it is only in these circumstances that its risk-benefit ratio proves to be favourable.^[6]^[9]

Adverse effects

As with other NSAIDs the principal side effects include: digestive complaints like nausea, discomfort, diarrhoea and bleeds or ulceration of the stomach, as well as headache, dizziness, nervousness, depression, drowsiness, insomnia, vertigo, hearing disturbances (such as tinnitus), high blood pressure, oedema, light sensitivity, skin reactions (including, albeit rarely, Stevens–Johnson syndrome and toxic epidermal necrolysis) and rarely, kidney failure, pancreatitis, liver damage, visual disturbances, pulmonary eosinophilia and fibrosing alveolitis.^[6] Compared to other NSAIDs it is more prone to causing gastrointestinal disturbances and serious skin reactions.^[6]

In October 2020, the U.S. Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.^[10]^[11] They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.^[10]^[11]

Mechanism of action

Piroxicam is an NSAID and, as such, is a non-selective COX inhibitor possessing both analgesic and antipyretic properties.^[6]

Chemical properties

Piroxicam exists as alkenol tautomer in organic solvents and as zwitterionic form in water.^[12]

History

The project that produced piroxicam began in 1962 at Pfizer; the first clinical trial results were reported in 1977, and the product launched in 1980 under the brand name "Feldene".^[8]^[13] Major patents expired in 1992^[8] and the drug is marketed worldwide under many brandnames.^[1]

References

^ ^a ^b ^c "International listings for piroxicam". Drugs.com. Retrieved 3 July 2015.
^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
^ "Active substance: piroxicam" (PDF). List of nationally authorised medicinal products. European Medicines Agency. 10 December 2020.
^ ^a ^b ^c ^d ^e ^f ^g Brayfield A, ed. (14 January 2014). "Piroxicam". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Archived from the original on 28 August 2021. Retrieved 24 June 2014.
^ "TGA Approved Terminology for Medicines, Section 1 – Chemical Substances" (PDF). Therapeutic Goods Administration, Department of Health and Ageing. Australian Government. July 1999. p. 97.
^ ^a ^b ^c ^d ^e Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. pp. 665, 673–674. ISBN 978-0-85711-084-8.
^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 519. ISBN 9783527607495.
^ ^a ^b ^c Lombardino JG, Lowe JA (October 2004). "The role of the medicinal chemist in drug discovery--then and now". Nature Reviews. Drug Discovery. 3 (10): 853–862. doi:10.1038/nrd1523. PMID 15459676. S2CID 11225541.. See: [1] Box 1: Discovery of piroxicam (1962–1980)
^ "Committee for medicinal products for human use (CHMP) opinion following an Article 31(2) referral for Piroxicam containing medicinal products" (PDF). European Medicines Agency. London, UK. 20 September 2007. Retrieved 24 June 2014.
^ ^a ^b "FDA Warns that Using a Type of Pain and Fever Medication in Second Half of Pregnancy Could Lead to Complications". U.S. Food and Drug Administration (FDA) (Press release). 15 October 2020. Retrieved 15 October 2020. This article incorporates text from this source, which is in the public domain.
^ ^a ^b "NSAIDs may cause rare kidney problems in fetuses". U.S. Food and Drug Administration. 21 July 2017. Retrieved 15 October 2020. This article incorporates text from this source, which is in the public domain.
^ Ivanova D, Deneva V, Nedeltcheva D, Kamounah FS, Gergov G, Hansen PE, Kawauchi S, Antonov L (2015). "Tautomeric transformations of piroxicam in solution: a combined experimental and theoretical study". RSC Advances. 5 (40): 31852–31860. Bibcode:2015RSCAd...531852I. doi:10.1039/c5ra03653d.
^ Weintraub M, Jacox RF, Angevine CD, Atwater EC (1977). "Piroxicam (CP 16171) in rheumatoid arthritis: a controlled clinical trial with novel assessment techniques". The Journal of Rheumatology. 4 (4): 393–404. PMID 342691.