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Naproxen

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Naproxen
Clinical data
Trade namesAleve, Anaprox, Apronax, Naprelan, Naprosyn
AHFS/Drugs.comMonograph
MedlinePlusa681029
License data
Pregnancy
category
  • AU: C
Routes of
administration		Oral.
ATC code
Legal status
Legal status
  • AU: S2 (Pharmacy medicine)
  • CA: OTC
  • UK: P (Pharmacy medicines)
  • US: WARNING[1]OTC
  • In Australia it is only Schedule 2 when in preparations containing no more than 15 days' supply. Otherwise it is schedule 4 (prescription-only).[2]
Pharmacokinetic data
Bioavailability95% (oral)
Protein binding99%
MetabolismHepatic (to 6-desmethylnaproxen)
Elimination half-life12–24 hours
ExcretionRenal
Identifiers
  • (+)-(S)-2-(6-methoxynaphthalen-2-yl)
    propanoic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.040.747 Edit this at Wikidata
Chemical and physical data
FormulaC14H14O3
Molar mass230.259 g/mol g·mol−1
3D model (JSmol)
  • C[C@@H](c1ccc2cc(ccc2c1)OC)C(=O)O
  • InChI=1S/C14H14O3/c1-9(14(15)16)10-3-4-12-8-13(17-2)6-5-11(12)7-10/h3-9H,1-2H3,(H,15,16)/t9-/m0/s1 checkY
  • Key:CMWTZPSULFXXJA-VIFPVBQESA-N checkY
  (verify)

Naproxen /nəˈprɒksən/ (INN; brand names: Aleve, Naprosyn and many others) usually sold as the sodium salt naproxen sodium is a nonsteroidal anti-inflammatory drug (NSAID) of the propionic acid class (which puts it in the same class as ibuprofen) and is commonly used for relief of a wide variety of pain, fever, swelling and stiffness.[3][4]: 665, 673  It is the preferred NSAID for long-term use in people with a high risk of cardiovascular (for example, heart attacks or strokes) complications, due to its relatively low risk of causing such complications. Naproxen has an intermediate risk of causing stomach ulcers as compared with ibuprofen, which is low risk, and indometacin, which is high risk.[5] In order to reduce the risk of stomach ulceration, it is often combined with a proton-pump inhibitor (a medication that reduces the production of stomach acid) during long-term treatment, in those with pre-existing stomach ulcers, or a history of developing stomach ulcers while on NSAIDs.[3][4]: 665, 673 

Medical uses

Naproxen is commonly used for the reduction of pain, fever, inflammation, and stiffness caused by conditions including migraine, osteoarthritis, kidney stones, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, menstrual cramps, tendinitis, and bursitis, among others. It is also used for the treatment of primary dysmenorrhea.[6]

Diagnostics

Naproxen has been utilized to differentiate between infectious fevers and those with neoplastic or connective tissue disease related fevers.[7]

Adverse effects

COX-2 selective and nonselective NSAIDs have been linked to increases in the number of serious and potentially fatal cardiovascular events, such as myocardial infarctions and strokes. Naproxen is, however, associated with the smallest overall cardiovascular risks.[8][9] Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug. The drug had roughly 50% of the associated risk of stroke as compared with ibuprofen and was also associated with a reduced number of myocardial infarctions as compared to control groups.[8] As with other non-COX-2 selective NSAIDs, naproxen can cause gastrointestinal problems, such as heartburn, constipation, diarrhea, ulcers and stomach bleeding.[10] Persons with a history of ulcers or inflammatory bowel disease should consult a doctor before taking naproxen.

It was found that high-dose naproxen induced near-complete suppression of platelet thromboxane throughout the dosing interval and appeared not to increase cardiovascular disease (CVD) risk, whereas other high-dose NSAID regimens had only transient effects on platelet COX-1 and were associated "with a small but definite vascular hazard". Conversely, naproxen was associated with higher rates of upper gastrointestinal bleeding complications in comparison to other NSAIDs.[9]

NSAID painkillers, such as naproxen, may interfere with and reduce the efficacy of SSRI antidepressants.[11][12]

Mechanism of action

Naproxen works by reversibly inhibiting both the COX-1 and COX-2 enzymes.[13][14][15][16][17]

Compound information

Naproxen is a member of the 2-arylpropionic acid (profen) family of NSAIDs.[18] The free acid is an odorless, white to off-white, crystalline substance. It is lipid-soluble and practically insoluble in water. It has a melting point of 152–155 °C.

Synthesis

Naproxen has been industrially produced by Syntex as follows:[19]

Other synthetic routes have also been discussed.[19]

Marketing and trade names

Naproxen and naproxen sodium are marketed under various trade names, including: Aleve, Accord, Anaprox, Antalgin, Apranax, Feminax Ultra, Flanax, Inza, Midol Extended Relief, Nalgesin, Naposin, Naprelan, Naprogesic, Naprosyn, Narocin, Proxen, Soproxen, Synflex and Xenobid.

Access restrictions

Naproxen was originally marketed as the prescription drug Naprosyn by Syntex in 1976, and naproxen sodium was first marketed under the trade name Anaprox in 1980. It remains a prescription-only drug in much of the world. In the United States, the Food and Drug Administration (FDA) approved its use as an over-the-counter (OTC) drug in 1994; OTC preparations in the U.S. are mainly marketed by Bayer HealthCare under the trade name Aleve and generic store brand formulations in 220 mg tablets. In Australia, packets of 275 mg tablets of naproxen sodium are Schedule 2 pharmacy medicines, with a maximum daily dose of five tablets or 1375 mg. In the United Kingdom, 250 mg tablets of naproxen were approved for OTC sale under the brand name Feminax Ultra in 2008, for the treatment of primary dysmenorrhoea in women aged 15 to 50.[20] In the Netherlands, 220 mg and 275 mg tablets are available OTC in drugstores, 550 mg is OTC only at pharmacies. Aleve became available over-the-counter in most provinces in Canada on 14 July 2009, but not British Columbia, Quebec or Newfoundland and Labrador;[21] it became available OTC in British Columbia in late January 2010.[22]

Research

Naproxen may have anti-viral activity against influenza. Specifically, it blocks the RNA-binding groove of the nucleoprotein of the virus, thereby preventing formation of the ribonucleoprotein complex, thus taking the vital nucleoproteins out of circulation.[23]

References

  1. ^ "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.
  2. ^ Template:Cite isbn
  3. ^ a b Template:Cite isbn
  4. ^ a b Template:Cite isbn
  5. ^ Richy, F; Bruyere, O; Ethgen, O; Rabenda, V; Bouvenot, G; Audran, M; Herrero-Beaumont, G; Moore, A; Eliakim, R; Haim, M; Reginster, JY (July 2004). "Time dependent risk of gastrointestinal complications induced by non-steroidal anti-inflammatory drug use: a consensus statement using a meta-analytic approach". Annals of the Rheumatic Diseases. 63 (7): 759–66. doi:10.1136/ard.2003.015925. PMC 1755051. PMID 15194568.
  6. ^ French L (2005). "Dysmenorrhea" (PDF). Am Fam Physician. 71 (2): 285–91. PMID 15686299.
  7. ^ Zell JA, Chang JC (November 2005). "Neoplastic fever: a neglected paraneoplastic syndrome". Support Care Cancer. 13 (11): 870–7. doi:10.1007/s00520-005-0825-4. PMID 15864658.
  8. ^ a b Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, Egger M, Jüni P. (2011). "Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis". BMJ. 342: c7086. doi:10.1136/bmj.c7086. PMC 3019238. PMID 21224324. c7086.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ a b Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, Bombardier C, Cannon C, Farkouh ME, FitzGerald GA, Goss P, Halls H, Hawk E, Hawkey C, Hennekens C, Hochberg M, Holland LE, Kearney PM, Laine L, Lanas A, Lance P, Laupacis A, Oates J, Patrono C, Schnitzer TJ, Solomon S, Tugwell P, Wilson K, Wittes J, Baigent C (August 2013). "Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials". Lancet. 382 (9894): 769–79. doi:10.1016/S0140-6736(13)60900-9. PMC 3778977. PMID 23726390.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ Naproxen. PubMed Health.
  11. ^ Tudor, Amy (2011-04-20) Why Painkillers Interfere with Anti-depressants. Healthcentral.com. Retrieved on 2013-09-20.
  12. ^ Warner-Schmidt JL, Vanover KE, Chen EY, Marshall JJ, Greengard P (May 2011). "Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans". Proc. Natl. Acad. Sci. U.S.A. 108 (22): 9262–7. doi:10.1073/pnas.1104836108. PMC 3107316. PMID 21518864.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ^ Duggan KC, Walters MJ, Musee J, Harp JM, Kiefer JR, Oates JA, Marnett LJ (November 2010). "Molecular basis for cyclooxygenase inhibition by the non-steroidal anti-inflammatory drug naproxen". J. Biol. Chem. 285 (45): 34950–9. doi:10.1074/jbc.M110.162982. PMC 2966109. PMID 20810665.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  14. ^ Hinz B, Cheremina O, Besz D, Zlotnick S, Brune K (April 2008). "Impact of naproxen sodium at over-the-counter doses on cyclooxygenase isoforms in human volunteers". Int J Clin Pharmacol Ther. 46 (4): 180–6. doi:10.5414/CPP46180. PMID 18397691.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Van Hecken A, Schwartz JI, Depré M, De Lepeleire I, Dallob A, Tanaka W, Wynants K, Buntinx A, Arnout J, Wong PH, Ebel DL, Gertz BJ, De Schepper PJ (October 2000). "Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers". J Clin Pharmacol. 40 (10): 1109–20. PMID 11028250.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ Gross GJ, Moore J (July 2004). "Effect of COX-1/COX-2 inhibition versus selective COX-2 inhibition on coronary vasodilator responses to arachidonic acid and acetylcholine". Pharmacology. 71 (3): 135–42. doi:10.1159/000077447. PMID 15161995.
  17. ^ Hawkey CJ (October 2001). "COX-1 and COX-2 inhibitors". Best Pract Res Clin Gastroenterol. 15 (5): 801–20. doi:10.1053/bega.2001.0236. PMID 11566042.
  18. ^ el Mouelhi M, Ruelius HW, Fenselau C, Dulik DM (1987). "Species-dependent enantioselective glucuronidation of three 2-arylpropionic acids. Naproxen, ibuprofen, and benoxaprofen". Drug Metab. Dispos. 15 (6): 767–72. PMID 2893700.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  19. ^ a b Harrington PJ, Lodewijk E (1997). "Twenty Years of Naproxen Technology". Org. Process Res. Dev. 1 (1): 72–76. doi:10.1021/op960009e.
  20. ^ "Medicines regulator approves availability of a new OTC medicine for period pain" (PDF) (Press release). Medicines and Healthcare products Regulatory Agency (MHRA). 1 April 2008.
  21. ^ "ALEVE – Welcome to Canada, Eh!" (PDF) (Press release). Bayer Health Care. 14 July 2009. Retrieved 24 March 2012.
  22. ^ "ALEVE® – Helping British Columbians with Joint and Arthritis Pain Get Back to Doing the Activities They Love". newswire.ca. 28 January 2010.
  23. ^ Lejal N, Tarus B, Bouguyon E, Chenavas S, Bertho N, Delmas B, Ruigrok RW, Di Primo C, Slama-Schwok A (May 2013). "Structure-based discovery of the novel antiviral properties of naproxen against the nucleoprotein of influenza A virus". Antimicrob. Agents Chemother. 57 (5): 2231–42. doi:10.1128/AAC.02335-12. PMC 3632891. PMID 23459490. {{cite journal}}: Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)CS1 maint: multiple names: authors list (link)
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