Naproxen – known and unknown faces of a non-steroidal anti-inflammatory drug in clinical practice. Part I Review article
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Published:
Jun 30, 2025
Keywords:
naproxen, nonsteroidal anti-inflammatory drugs, pain, headache, fever
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Abstract
Naproxen is a well-known, prescription and over-the-counter nonsteroidal anti-inflammatory drug (NSAID), whose analgesic, anti-inflammatory, and antipyretic properties are used in the treatment of numerous pain syndromes, both acute and chronic. Its pharmacological activity includes, in addition to inhibiting cyclooxygenases, other multifaceted mechanisms of action, including blocking purine receptors and antiviral effects confirmed in in vitro and human studies.
Numerous clinical studies have confirmed its effectiveness in the treatment of conditions such as rheumatoid arthritis, osteoarthritis, gout, nonspecific low back pain, primary menstrual pain, headaches, and fever. Its relatively rapid analgesic effect, long half-life, and well-established safety profile among NSAIDs make it an effective drug used in everyday medical practice. This paper presents key aspects of naproxen, including its mechanisms of action, possible side effects, efficacy and safety in pain relief in many conditions, as well as in the treatment of fever and colds.
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How to Cite
Bitner-Bieleszuk, M., Bryła, A., & Kocot-Kępska, M. (2025). Naproxen – known and unknown faces of a non-steroidal anti-inflammatory drug in clinical practice. Part I. Medycyna Faktow (J EBM), 18(2(67), 277-282. https://doi.org/10.24292/01.MF.0225.16
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References
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9. Cicala C, Ianaro A, Fiorucci S et al. NO-naproxen modulates inflammation, nociception and downregulates T cell response in rat Freund’s adjuvant arthritis. Br J Pharmacol. 2000;130(6): 1399-405.
10. Aras H, Cağlayan F, Güncü GN et al. Effect of systemically administered naproxen sodium on clinical parameters and myeloperoxidase and elastase- like activity levels in gingival crevicular fluid. J Periodontol. 2007; 78(5): 868-73.
11. Glazer PA, Rosenwasser MP, Ratcliffe A. The effect of naproxen and interleukin-1 on proteoglycan catabolism and on neutral metalloproteinase activity in normal articular cartilage in vitro. J Clin Pharmacol. 1993; 33(2): 109-14.
12. Ounissi-Benkalha H, Pelletier JP, Tardif G et al. In vitro effects of 2 antirheumatic drugs on the synthesis and expression of proinflammatory cytokines in synovial membranes from patients with rheumatoid arthritis. J Rheumatol. 1996; 23(1): 16-23.
13. Smith CE, Soti S, Jones TA et al. Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors. Cell Chem Biol. 2017; 24(3): 281-92.
14. Hautaniemi T, Petrenko N, Skorinkin A et al. The inhibitory action of the antimigraine nonsteroidal anti-inflammatory drug naproxen on P2X3 receptor-mediated responses in rat trigeminal neurons. Neuroscience. 2012; 209: 32-8.
15. Brutzkus JC, Shahrokhi M, Varacallo MA. Naproxen. In: StatPearls. Treasure Island (FL). StatPearls Publishing; 2020. https://www.ncbi.nlm.nih.gov/books/NBK525965/.
16. Terrier O, Dilly S, Pizzorno A, Chalupska D et al. Antiviral Properties of the NSAID Drug Naproxen Targeting the Nucleoprotein of SARS-CoV-2 Coronavirus. Molecules. 2021; 26(9): 2593.
17. Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling. Federal Register. 2014.
18. Ocena bezpieczeństwa stosowania leku w czasie karmienia piersią. Wydawnictwo Farmaceutyczne, 2020.
19. Bruno R, Iliadis A, Jullien I et al. Naproxen kinetics in synovial fluid of patients with osteoarthritis. Br J Clin Pharmacol. 1988; 26(1): 41-4.
20. Paglia MDG, Silva MT, Lopes LC et al. Use of corticoids and non-steroidal anti-inflammatories in the treatment of rheumatoid arthritis: Systematic review and network meta-analysis. PLOS ONE. 2021; 16(4): e0248866.
21. Fan M, Liu J, Zhao B et al. Indirect comparison of NSAIDs for ankylosing spondylitis: Network meta‑analysis of randomized, double‑blinded, controlled trials. Exp Ther Med. 2020; 19(4): 3031-41.
22. Roddy E, Clarkson K, Blagojevic-Bucknall M et al. Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care. Ann Rheum Dis. 2020; 79(2): 276-84.
23. Smith SR, Deshpande BR, Collins JE et al. Comparative pain reduction of oral non-steroidal anti-inflammatory drugs and opioids for knee osteoarthritis: systematic analytic review. Osteoarthritis Cartilage. 2016; 24(6): 962-72.
24. Jevsevar DS, Shores PB, Mullen K et al. Mixed Treatment Comparisons for Nonsurgical Treatment of Knee Osteoarthritis: A Network Meta-analysis. J Am Acad Orthop Surg. 2018; 26(9): 325-36.
25. Levin OS, Skoromets AA, Tabeeva GR et al. The efficacy and safety of naproxen in the treatment of nonspecific lumbalgia: the results of an open multi-center study (NEST). Zhurnal Nevrol Psikhiatrii Im SS Korsakova. 2019; 119(5): 27.
26. van Der Gaag WH, Roelofs PD, Enthoven WT et al. Non-steroidal anti-inflammatory drugs for acute low back pain. Cochrane Back and Neck Group. Cochrane Database Syst Rev. 2020; 2020(4). http://doi.wiley.com/10.1002/14651858.CD013581.
27. Grøvle L, Hasvik E, Holst R et al. Efficacy of naproxen in patients with sciatica: multicenter, randomized, double-blind, placebo-controlled trial. Pain. 2024; 165(11): 2606-14.
28. Derry S, Moore RA, Gaskell H et al. Topical NSAIDs for acute musculoskeletal pain in adults. Cochrane Database Syst Rev. 2015; 2015(6): CD007402.
29. Thorling J, Linden B, Berg R et al. A double-blind comparison of naproxen gel and placebo in the treatment of soft tissue injuries. Curr Med Res Opin. 1990; 12(4): 242-8.
2. Charakterystyka Produktu Leczniczego – Naproksen.
3. Charakterystyka Produktu Leczniczego – Naproksen sodowy.
4. Sevelius H, Runkel R, Segre E et al. Bioavailability of Naproxen Sodium and Its Relationship to Clinical Analgesic Effects. Br J Clin Pharmac 1980; 10: 259-26.
5. Law S, Derry S, Moore RA. Sumatriptan plus naproxen for the treatment of acute migraine attacks in adults. Cochrane Database Syst Rev. 2016; 4(4): CD008541.
6. Hinz B, Cheremina O, Besz D, Zlotnick S, Brune K. Impact of naproxen sodium at over-the-counter doses on cyclooxygenase isoforms in human volunteers. Int J Clin Pharmacol Ther. 2008; 46(04):180-6.
7. Woroń J. Miejsce naproksenu w farmakoterapii bólu i gorączki. Co wiemy w 2022 roku? Med Faktów. 2022; 4(57): 401-3.
8. Shahid W, Ejaz SA, al-Rashida M et al. Identification of NSAIDs as lipoxygenase inhibitors through highly sensitive chemiluminescence method, expression analysis in mononuclear cells and computational studies. Bioorganic Chem. 2021;110: 104818.
9. Cicala C, Ianaro A, Fiorucci S et al. NO-naproxen modulates inflammation, nociception and downregulates T cell response in rat Freund’s adjuvant arthritis. Br J Pharmacol. 2000;130(6): 1399-405.
10. Aras H, Cağlayan F, Güncü GN et al. Effect of systemically administered naproxen sodium on clinical parameters and myeloperoxidase and elastase- like activity levels in gingival crevicular fluid. J Periodontol. 2007; 78(5): 868-73.
11. Glazer PA, Rosenwasser MP, Ratcliffe A. The effect of naproxen and interleukin-1 on proteoglycan catabolism and on neutral metalloproteinase activity in normal articular cartilage in vitro. J Clin Pharmacol. 1993; 33(2): 109-14.
12. Ounissi-Benkalha H, Pelletier JP, Tardif G et al. In vitro effects of 2 antirheumatic drugs on the synthesis and expression of proinflammatory cytokines in synovial membranes from patients with rheumatoid arthritis. J Rheumatol. 1996; 23(1): 16-23.
13. Smith CE, Soti S, Jones TA et al. Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors. Cell Chem Biol. 2017; 24(3): 281-92.
14. Hautaniemi T, Petrenko N, Skorinkin A et al. The inhibitory action of the antimigraine nonsteroidal anti-inflammatory drug naproxen on P2X3 receptor-mediated responses in rat trigeminal neurons. Neuroscience. 2012; 209: 32-8.
15. Brutzkus JC, Shahrokhi M, Varacallo MA. Naproxen. In: StatPearls. Treasure Island (FL). StatPearls Publishing; 2020. https://www.ncbi.nlm.nih.gov/books/NBK525965/.
16. Terrier O, Dilly S, Pizzorno A, Chalupska D et al. Antiviral Properties of the NSAID Drug Naproxen Targeting the Nucleoprotein of SARS-CoV-2 Coronavirus. Molecules. 2021; 26(9): 2593.
17. Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling. Federal Register. 2014.
18. Ocena bezpieczeństwa stosowania leku w czasie karmienia piersią. Wydawnictwo Farmaceutyczne, 2020.
19. Bruno R, Iliadis A, Jullien I et al. Naproxen kinetics in synovial fluid of patients with osteoarthritis. Br J Clin Pharmacol. 1988; 26(1): 41-4.
20. Paglia MDG, Silva MT, Lopes LC et al. Use of corticoids and non-steroidal anti-inflammatories in the treatment of rheumatoid arthritis: Systematic review and network meta-analysis. PLOS ONE. 2021; 16(4): e0248866.
21. Fan M, Liu J, Zhao B et al. Indirect comparison of NSAIDs for ankylosing spondylitis: Network meta‑analysis of randomized, double‑blinded, controlled trials. Exp Ther Med. 2020; 19(4): 3031-41.
22. Roddy E, Clarkson K, Blagojevic-Bucknall M et al. Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care. Ann Rheum Dis. 2020; 79(2): 276-84.
23. Smith SR, Deshpande BR, Collins JE et al. Comparative pain reduction of oral non-steroidal anti-inflammatory drugs and opioids for knee osteoarthritis: systematic analytic review. Osteoarthritis Cartilage. 2016; 24(6): 962-72.
24. Jevsevar DS, Shores PB, Mullen K et al. Mixed Treatment Comparisons for Nonsurgical Treatment of Knee Osteoarthritis: A Network Meta-analysis. J Am Acad Orthop Surg. 2018; 26(9): 325-36.
25. Levin OS, Skoromets AA, Tabeeva GR et al. The efficacy and safety of naproxen in the treatment of nonspecific lumbalgia: the results of an open multi-center study (NEST). Zhurnal Nevrol Psikhiatrii Im SS Korsakova. 2019; 119(5): 27.
26. van Der Gaag WH, Roelofs PD, Enthoven WT et al. Non-steroidal anti-inflammatory drugs for acute low back pain. Cochrane Back and Neck Group. Cochrane Database Syst Rev. 2020; 2020(4). http://doi.wiley.com/10.1002/14651858.CD013581.
27. Grøvle L, Hasvik E, Holst R et al. Efficacy of naproxen in patients with sciatica: multicenter, randomized, double-blind, placebo-controlled trial. Pain. 2024; 165(11): 2606-14.
28. Derry S, Moore RA, Gaskell H et al. Topical NSAIDs for acute musculoskeletal pain in adults. Cochrane Database Syst Rev. 2015; 2015(6): CD007402.
29. Thorling J, Linden B, Berg R et al. A double-blind comparison of naproxen gel and placebo in the treatment of soft tissue injuries. Curr Med Res Opin. 1990; 12(4): 242-8.