<p>Indometacin, or indomethacin, is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic properties. NSAIDs consist of agents that are structurally unrelated; the NSAID chemical classification of indometacin is an indole-acetic acid derivative with the chemical name 1- (p-chlorobenzoyl)25-methoxy-2-methylindole-3-acetic acid.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Lucas S: The Pharmacology of Indomethacin. Headache. 2016 Feb;56(2):436-46. doi: 10.1111/head.12769. Epub 2016 Feb 11. (PubMed ID 26865183)" href="#reference-A177871">1</a></sup> The pharmacological effect of indometacin is not fully understood, however, it is thought to be mediated through potent and nonselective inhibition of the enzyme cyclooxygenase (COX), which is the main enzyme responsible for catalyzes the rate-limiting step in prostaglandin and thromboxane biosynthesis via the arachidonic acid (AA) pathway. Indometacin was first discovered in 1963 and it was first approved for use in the U.S. by the Food and Drug Administration in 1965, <sup class="text-reference-group"><a class="reference-popover-link" data-content="HART FD, BOARDMAN PL: INDOMETHACIN: A NEW NON-STEROID ANTI-INFLAMMATORY AGENT. Br Med J. 1963 Oct 19;2(5363):965-70. (PubMed ID 14056924)" href="#reference-A486">10</a></sup> along with other acetic acid derivatives such as <a href="https://go.drugbank.com/drugs/DB00586">diclofenac</a> and <a href="https://go.drugbank.com/drugs/DB00605">sulindac</a> that were also developed during the 1960s.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Lucas S: The Pharmacology of Indomethacin. Headache. 2016 Feb;56(2):436-46. doi: 10.1111/head.12769. Epub 2016 Feb 11. (PubMed ID 26865183)" href="#reference-A177871">1</a></sup> Since then, indometacin has been extensively studied in clinical trials as one of the most potent NSAIDs in blocking prostaglandin synthesis and was among the first NSAIDs to be used in the symptomatic treatment of migraine and for headaches that eventually became known as “indomethacin-responsive” headache disorders.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Lucas S: The Pharmacology of Indomethacin. Headache. 2016 Feb;56(2):436-46. doi: 10.1111/head.12769. Epub 2016 Feb 11. (PubMed ID 26865183)" href="#reference-A177871">1</a></sup> </p><p>Most commonly used in rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute shoulder pains, and acute gouty arthritis, indometacin is currently available as oral capsules as well as other methods of administration, including rectal and intravenous formulations. Intravenous indometacin is administered to close a hemodynamically significant patent ductus arteriosus, as indicated by clinical evidence, in premature infants.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Indocin I.V. (indomethacin for injection) - FDA Label" href="#reference-L10553">14</a></sup> Ophthalmic indometacin has been studied and used in the symptomatic treatment of postoperative ocular inflammation and pain and/or complications after cataract surgery. Although deemed effective in reducing ocular inflammation in clinical studies, topical NSAIDs were also associated with a potential reduction in corneal sensitivity accompanied by an increased risk of superficial punctate keratitis and subjective symptoms of discomfort, including pain, burning or pricking, or a tingling sensation after instillation into the cul‐de‐sac.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Weber M, Kodjikian L, Kruse FE, Zagorski Z, Allaire CM: Efficacy and safety of indomethacin 0.1% eye drops compared with ketorolac 0.5% eye drops in the management of ocular inflammation after cataract surgery. Acta Ophthalmol. 2013 Feb;91(1):e15-21. doi: 10.1111/j.1755-3768.2012.02520.x. Epub 2012 Sep 12. (PubMed ID 22970738)" href="#reference-A177949">6</a></sup></p>