Comparison of Gastrointestinal Safety of NSAID Drugs Ibuprofen, Naproxen, and Celecoxib at Various Doses: A Literature Review
Article metrics
OJS usage and citation sourcesViews and downloads are recorded by OJS; statistics processing may be delayed. A dash means the source count is unavailable. Search Google Scholar
Article Sidebar
Naila Permatasari, Mukarromah Dita Putri, Namira Azzani (2026). Comparison of Gastrointestinal Safety of NSAID Drugs Ibuprofen, Naproxen, and Celecoxib at Various Doses: A Literature Review. Journal of Pharmaceutical and Sciences, JPS Volume 9 Nomor 4 (2026). https://doi.org/10.36490/journal-jps.com.v9i4.2003
Main Article Content
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to manage pain and inflammation, particularly in osteoarthritis and rheumatoid arthritis, but their use may cause gastrointestinal adverse effects ranging from dyspepsia to ulceration and gastrointestinal bleeding. This literature review aimed to compare the gastrointestinal safety of ibuprofen, naproxen, and celecoxib across different doses and treatment regimens. Literature was reviewed from studies published between January 2016 and March 2026, with attention to NSAID type, dose, frequency, treatment duration, patient characteristics, concomitant aspirin or corticosteroid use, gastroprotective therapy, and gastrointestinal outcomes. The reviewed studies showed that celecoxib generally had a lower incidence of gastrointestinal events than ibuprofen and naproxen in several treatment regimens. In the PRECISION trial, clinically significant gastrointestinal events occurred less frequently with celecoxib than with ibuprofen and naproxen, while the CONCERN trial demonstrated a lower rate of recurrent upper gastrointestinal bleeding with celecoxib plus esomeprazole than with naproxen plus esomeprazole in patients at high gastrointestinal risk. However, gastrointestinal safety was also influenced by treatment duration, aspirin or corticosteroid use, patient characteristics, and gastroprotective therapy. Differences in dose expressed in milligrams could not be directly interpreted as equivalent exposure between NSAIDs. Therefore, gastrointestinal safety should be assessed based on the overall treatment regimen and patient risk profile rather than dose alone
Article Details
Section
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
How to Cite
References
[1] Bakhriansyah M, Souverein PC, De Boer A, Klungel OH. Gastrointestinal toxicity among patients taking selective COX‐2 inhibitors or conventional NSAIDs, alone or combined with proton pump inhibitors: a case-control study. Pharmacoepidemiol Drug Saf 2017;26:1141–8. https://doi.org/10.1002/pds.4183.
[2] Sostres C, Carrera-Lasfuentes P, Lanas A. Non-steroidal anti-inflammatory drug related upper gastrointestinal bleeding: types of drug use and patient profiles in real clinical practice. Curr Med Res Opin 2017;33:1815–20. https://doi.org/10.1080/03007995.2017.1338178.
[3] Shin S. Safety of celecoxib versus traditional nonsteroidal anti-inflammatory drugs in older patients with arthritis. J Pain Res 2018;Volume 11:3211–9. https://doi.org/10.2147/JPR.S186000.
[4] Ruiz B, Aguirre U, Estany-Gestal A, Rodella L, Ruiz P, Figueiras A, et al. Only full adherence to proton pump inhibitors protects against drug-induced upper gastrointestinal bleeding. Eur J Clin Pharmacol 2018;74:1503–11. https://doi.org/10.1007/s00228-018-2523-4.
[5] Gordo AC, Walker C, Armada B, Zhou D. Efficacy of celecoxib versus ibuprofen for the treatment of patients with osteoarthritis of the knee: A randomized double-blind, non-inferiority trial. J Int Med Res 2017;45:59–74. https://doi.org/10.1177/0300060516673707.
[6] Nissen SE, Yeomans ND, Solomon DH, Lüscher TF, Libby P, Husni ME, et al. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. N Engl J Med 2016;375:2519–29. https://doi.org/10.1056/NEJMoa1611593.
[7] Yeomans ND, Graham DY, Husni ME, Solomon DH, Stevens T, Vargo J, et al. Randomised clinical trial: gastrointestinal events in arthritis patients treated with celecoxib, ibuprofen or naproxen in the PRECISION trial. Aliment Pharmacol Ther 2018;47:1453–63. https://doi.org/10.1111/apt.14610.
[8] Chan FKL, Ching JYL, Tse YK, Lam K, Wong GLH, Ng SC, et al. Gastrointestinal safety of celecoxib versus naproxen in patients with cardiothrombotic diseases and arthritis after upper gastrointestinal bleeding (CONCERN): an industry-independent, double-blind, double-dummy, randomised trial. The Lancet 2017;389:2375–82. https://doi.org/10.1016/S0140-6736(17)30981-9.
[9] Park MS, Kang C-N, Lee W-S, Kim H-J, Lee S, Kim JH, et al. A comparative study of the efficacy of NAXOZOL compared to celecoxib in patients with osteoarthritis. PLOS ONE 2020;15:e0226184. https://doi.org/10.1371/journal.pone.0226184.
[10] Reed GW, Abdallah MS, Shao M, Wolski K, Wisniewski L, Yeomans N, et al. Effect of Aspirin Coadministration on the Safety of Celecoxib, Naproxen, or Ibuprofen. J Am Coll Cardiol 2018;71:1741–51. https://doi.org/10.1016/j.jacc.2018.02.036.
[11] Jiang S, Wang M, Ren X, Jiang Z, Zhu Q, Dai S, et al. Risk factors for drug-related gastrointestinal ulcer:a retrospective pharmacovigilance study. Front Pharmacol 2026;17:1784428. https://doi.org/10.3389/fphar.2026.1784428.
[12] Narum S, Westergren T, Klemp M. Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ Open 2014;4:e004587. https://doi.org/10.1136/bmjopen-2013-004587.