magazinelogo

Advance in Biological Research

ISSN Online: 2635-0319 CODEN: ABRDF6
Frequency: Instant publication Email: abr@hillpublish.com
Total View: 546447 Downloads: 56416 Citations: 33 (From Dimensions)

Volumes & Issues

Current Issue

All Volumes

ArticleOpen Access http://dx.doi.org/10.26855/abr.2026.06.001

Indomethacin in Pharmaceutical and Clinical Practices: A Narrative Review of Its Multifaceted Roles

Anurag Mishra1,*, Satya Narayan Mishra2

1Department of Biochemistry, ISD College, University of Allahabad, Prayagraj 211004, Uttar Pradesh, India.

2Krishna Institute of Pharmacy, Dr. APJ Abdul Kalam Technical University, Mirzapur 231211, Uttar Pradesh, India.

*Corresponding author: Anurag Mishra

Published: May 26, 2026

Abstract

Indomethacin is now considered an anti-inflammatory drug in Pharmaceutical and Clinical practices. This is a non-steroid anti-inflammatory drug (NSAID) approved in 1965, which inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin (PG) synthesis and expression in cells/tissues. Beyond its classical anti-inflammatory, analgesic, and antipyretic effects, Indomethacin exhibits promising pharmacological properties, including anti-viral (e.g., against SARS-CoV-2), anti-cancer, neuroprotective, and anti-tuberculosis activities. However, in traumatic brain injury, Indomethacin acts as a cerebral vasoconstrictor by reducing PG production and lowering intracranial pressure (ICP). Moreover, in pregnancy, it reduces labor pain through regulating PG, interleukin-8 (IL-8), and nuclear factor kappa B (NF-kB) levels. Mechanistically, inflammatory cells produce cytokines, PG, and reactive oxygen species (ROS), which exacerbate tissues and organs’ homeostasis. According to COX selectivity, the anti-inflammatory potency of NSAIDs decreases as follows: Indomethacin > Naproxen > Ibuprofen > Phenylbutazone > Aspirin. This review summarizes unexplored roles, mechanistic insights, and potential therapeutic applications, aiming to guide future research. 

Keyword

Indomethacin; Bcl-2 protein; SARS-CoV-2; tuberculosis; prostaglandins; COX

References

[1] Gliszczyńska A, Gliszczyńska G, Nowaczyk M, Trabocchi A, Lenci E. Lipid formulations and bioconjugation strategies for indomethacin therapeutic advances. Molecules. 2021;26(6):1576.
https://doi.org/10.3390/molecules26061576

[2] Nalamachu S, Wortmann R. Role of indomethacin in acute pain and inflammation management: a review of the literature. Postgrad Med. 2014;126(4):92-7.
https://doi.org/10.3810/pgm.2014.07.2787

[3] Shekhar N, Kaur H, Sarma P, Prakash A, Medhi B. Indomethacin: an exploratory study of antiviral mechanism and host-pathogen inter-action in COVID-19. Expert Rev Anti Infect Ther. 2022;20(3):383-90.
https://doi.org/10.1080/14787210.2022.1990756

[4] Kiguchiya A, Teraoka R, Sakane T. Utility of solid-state UV/Vis spectra on the evaluation of photostability of indomethacin crystals. Chem Pharm Bull (Tokyo). 2018;66(9):892-5.
https://doi.org/10.1248/cpb.c18-00389

[5] Lucas S. The pharmacology of indomethacin. Headache. 2016;56(2):436-46.
https://doi.org/10.1111/head.12769

[6] Zhou Y, Hancock JF, Lichtenberger LM. The nonsteroidal anti-inflammatory drug indomethacin induces heterogeneity in lipid membranes: potential implication for its diverse biological action. PLoS One. 2010;5(1):e8811.
https://doi.org/10.1371/journal.pone.0008811

[7] Summ O, Evers S. Mechanism of action of indomethacin in indomethacin-responsive headaches. Curr Pain Headache Rep. 2013;17(4):327.
https://doi.org/10.1007/s11916-013-0327-x

[8] Lucas S. The pharmacology of indomethacin. Headache. 2016;56(2):436-46.
https://doi.org/10.1111/head.12769

[9] Draper MP, Martell RL, Levy SB. Indomethacin-mediated reversal of multidrug resistance and drug efflux in human and murine cell lines overexpressing MRP, but not P-glycoprotein. Br J Cancer. 1997;75(6):810-5. https://doi.org/10.1038/bjc.1997.145

[10] Kim WY, Won M, Koo S, Zhang X, Kim JS. Mitochondrial H2Sn-mediated anti-inflammatory theranostics. Nano-Micro Lett. 2021;13(1):168.
https://doi.org/10.1007/s40820-021-00689-1

[11] Tan J, Deng Z, Liu G, Hu J, Liu S. Anti-inflammatory polymersomes of redox-responsive polyprodrug amphiphiles with inflammation-triggered indomethacin release characteristics. Biomaterials. 2018;178:608-19.
https://doi.org/10.1016/j.biomaterials.2018.03.035

[12] Little P. Non-steroidal anti-inflammatory drugs and Covid-19. BMJ. 2020;368:m1185.
https://doi.org/10.1136/bmj.m1185

[13] Xu T, Gao X, Wu Z, Selinger DW, Zhou Z. Indomethacin has a potent antiviral activity against SARS CoV-2 in vitro and canine coronavirus in vivo. bioRxiv [Preprint]. 2020 Apr 2:2020.04.01.017624. https://doi.org/10.1101/2020.04.01.017624

[14] Alkotaji M, Al-Zidan RN. Indomethacin: can it counteract bradykinin effects in COVID-19 patients? Curr Pharmacol Rep. 2021;7(3):102-8.
https://doi.org/10.1007/s40495-021-00257-6

[15] Raghav N, Kamboj RC, Singh H. Effect of some steroidal and non-steroidal anti-inflammatory drugs on purified goat brain, cathepsin L. Indian J Med Res. 1993;98:188-92.

[16] Amici C, Di Caro A, Ciucci A, Chiappa L, Castilletti C, Martella V, et al. Indomethacin has a potent antiviral activity against SARS coro-navirus. Antivir Ther. 2006;11(8):1021-30.
 https://doi.org/10.1177/135965350601100803

[17] Amici C, La Frazia S, Brunelli C, Balsamo M, Angelini M, Santoro MG. Inhibition of viral protein translation by indomethacin in vesicular stomatitis virus infection: role of eIF2α kinase PKR. Cell Microbiol. 2015;17(9):1391-404. https://doi.org/10.1111/cmi.12439

[18] Brunelli C, Amici C, Angelini M, Fracassi C, Belardo G, Santoro MG. The non-steroidal anti-inflammatory drug indomethacin activates the eIF2α kinase PKR, causing a translational block in human colorectal cancer cells. Biochem J. 2012;443(2):379-86.

https://doi.org/10.1042/BJ20111436

[19] Ravichandran R, Purna P, Vijayaraghavalu S, Teja Kalavakollu RT, Gaidhane S, Krishna Kumar R. Use of indomethacin in COVID-19 patients-experience from two medical centres. J Indian Med Assoc. 2021;119(7):42-5.

[20] Ravichandran R, Mohan SK, Sukumaran SK, Kamaraj B, Thiruvengadam R, Subramani K, et al. An open label randomized clinical trial of indomethacin for mild and moderate hospitalised Covid-19 patients. Sci Rep. 2022;12:6413.
https://doi.org/10.1038/s41598-022-10370-1

[21] Gordon DE, Hiatt J, Bouhaddou M, Rezelj VV, Ulferts S, Braberg H, et al. Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science. 2020;370(6521):eabe9403.
https://doi.org/10.1126/science.abe9403

[22] Rajan R, Subramanian S, Clark C. Low dose indomethacin for symptomatic treatment of COVID-19. Int J Med Rev Case Rep. 2020;4(9):6-7.
https://doi.org/10.5455/IJMRCR.low-dose-indomethacin-covid-19

[23] Kanakaraj A, Ravichandran R. Low dose indomethacin in the outpatient treatment of COVID-19 in kidney transplant recipients: a case series. OALib. 2020;07(10):1-8.
https://doi.org/10.4236/oalib.1106689

[24] Chen C, Nie Y, Xu G, Yang X, Fang H, Hou X. Design, synthesis and preliminary bioactivity studies of indomethacin derivatives as Bcl-2/Mcl-1 dual inhibitors. Bioorg Med Chem. 2019;27(13):2771-83. https://doi.org/10.1016/j.bmc.2019.05.003

[25] Curry JM, Besmer DM, Erick TK, Steuerwald N, Roy LD, Grover P, et al. Indomethacin enhances anti-tumor efficacy of a MUC1 peptide vaccine against breast cancer in MUC1 transgenic mice. PLoS One. 2019;14(11):e0224309. 

https://doi.org/10.1371/journal.pone.0224309

[26] Martín-Saborido C, López-Alcalde J, Ciapponi A, Sánchez Martín CE, Garcia Garcia E, Escobar Aguilar G, et al. Indomethacin for intra-cranial hypertension secondary to severe traumatic brain injury in adults. Cochrane Database Syst Rev. 2019;2019(11):CD011725.

https://doi.org/10.1002/14651858.CD011725.pub2

[27] Revuelta M, Zamarrón A, Fortes J, Rodríguez-Boto G, Gutiérrez-González R. Neuroprotective effect of indomethacin in normal perfusion pressure breakthrough phenomenon. Sci Rep. 2020;10(1):13811. https://doi.org/10.1038/s41598-020-72461-1

[28] Summ O, Andreou AP, Akerman S, Holland PR, Hoffmann J, Goadsby PJ. Differential actions of indomethacin: clinical relevance in headache. Pain. 2021;162(2):591-9.
 https://doi.org/10.1097/j.pain.0000000000002032

[29] Laprairie RB, Mohamed KA, Zagzoog A, Kelly MEM, Stevenson LA, Pertwee R, et al. Indomethacin enhances type 1 cannabinoid re-ceptor signaling. Front Mol Neurosci. 2019;12:257. https://doi.org/10.3389/fnmol.2019.00257

[30] Rovers JFJ, Thomissen IJC, Janssen LCE, Lingius S, Wieland BV, Dieleman JP, et al. The relationship between antenatal indomethacin as a tocolytic drug and neonatal outcomes: a retrospective cohort study. J Matern Fetal Neonatal Med. 2021;34(18):2945-51.

https://doi.org/10.1080/14767058.2019.1674807

[31] Abou-Ghannam G, Usta IM, Nassar AH. Indomethacin in pregnancy: applications and safety. Am J Perinatol. 2012;29(3):175-86. 

https://doi.org/10.1055/s-0031-1284227

[32] Tomida S, Aizawa K, Nishida N, Aoki H, Imai Y, Nagai R, Suzuki T. Indomethacin reduces rates of aortic dissection and rupture of the abdominal aorta by inhibiting monocyte/macrophage accumulation in a murine model. Sci Rep. 2019;9(1):10756.

https://doi.org/10.1038/s41598-019-46673-z

[33] Sloan B. Indomethacin for burning scrotum syndrome: September 2021. J Am Acad Dermatol. 2021;85(3):568.

https://doi.org/10.1016/j.jaad.2021.06.851

[34] Tonby K, Wergeland I, Lieske NV, Kvale D, Taskén K, Dyrhol-Riise AM. The COX- inhibitor indomethacin reduces Th1 effector and T regulatory cells in vitro in Mycobacterium tuberculosis infection. BMC Infect Dis. 2016;16:599. 

https://doi.org/10.1186/s12879-016-1938-8

[35] Chamoun-Emanuelli AM, Bryan LK, Cohen ND, Tetrault TL, Szule JA, Barhoumi R, et al. NSAIDs disrupt intestinal homeostasis by suppressing macroautophagy in intestinal epithelial cells. Sci Rep. 2019;9(1):14534. https://doi.org/10.1038/s41598-019-51067-2

[36] Bykova AV, Bykov VV, Stankevich SA, Vengerovskii AI, Udut VV. Effect of ester derivative of indomethacin on immune inflammation. Bull Exp Biol Med. 2021;170(4):440-3.
 https://doi.org/10.1007/s10517-021-05082-x

[37] Fearon AD, Stokes GY. Thermodynamics of indomethacin adsorption to phospholipid membranes. J Phys Chem B. 2017;121(46):10508-18.
https://doi.org/10.1021/acs.jpcb.7b08359

[38] Herminghaus A, Buitenhuis AJ, Schulz J, Truse R, Vollmer C, Relja B, et al. Indomethacin increases the efficacy of oxygen utilization of colonic mitochondria and uncouples hepatic mitochondria in tissue homogenates from healthy rats. Front Med (Lausanne). 2020;7:463.

https://doi.org/10.3389/fmed.2020.00463

[39] Munjal A, Allam AE. Indomethacin. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [updated 2021 Dec 4; cited 2023 Mar 13]. Available from: 
https://www.ncbi.nlm.nih.gov/books/NBK555936/

[40] El-Mashad AE, El-Mahdy H, El Amrousy D, Elgendy M. Comparative study of the efficacy and safety of paracetamol, ibuprofen, and indomethacin in closure of patent ductus arteriosus in preterm neonates. Eur J Pediatr. 2017;176(2):233-40.

https://doi.org/10.1007/s00431-016-2828-1

Copyright

© 2026 by the author(s).
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) license, which permits non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited and is not modified or adapted.
https://creativecommons.org/licenses/by-nc-nd/4.0/

How to cite this paper

Indomethacin in Pharmaceutical and Clinical Practices: A Narrative Review of Its Multifaceted Roles

How to cite this paper: Anurag Mishra, Satya Narayan Mishra. (2026)  Indomethacin in Pharmaceutical and Clinical Practices: A Narrative Review of Its Multifaceted RolesAdvance in Biological Research, 7(1), 1-10.

DOI: http://dx.doi.org/10.26855/abr.2026.06.001