API: Indomethacin

What Is Indomethacin and How Does it Work?

Indomethacin is an non-steroidal anti-inflammatory drug (NSAID) that has anti-inflammatory, analgesic, and antipyretic activity. It belongs to the acetic acid class of NSAIDs and works by inhibiting the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. These enzymes are required for the synthesis of prostaglandins, which are hormone-like molecules that regulate the body’s inflammatory response to injury.1 The anti-inflammatory and analgesic properties of indomethacin also derive from its ability to uncouple oxidative phosphorylation in mitochondria and inhibit the motility of polymorphonuclear leukocytes.2 Indomethacin is primarily used to treat moderate to severe pain and inflammation.


Indomethacin has been approved to treat3:

  • Arthritis: Indomethacin is used to relieve moderate to severe pain from rheumatoid arthritis (arthritis caused by inflammation of the joints), osteoarthritis (arthritis caused by breakdown of the lining of the joints), and ankylosing spondylitis (arthritis caused by inflammation of the joints in the spine). It can also treat gouty arthritis (gout), which is characterized by sudden, burning pain in a joint, most commonly the big toe.
  • Acute Shoulder Pain: Indomethacin provides effective treatment for acute shoulder pain caused by either bursitis or tendinitis.
  • Fever Reduction: Indomethacin is a powerful antipyretic.
  • Patent Ductus Arteriosus (PDA): Indomethacin injection is used to treat PDA in premature infants when other medical treatments have failed after 48 hours. PDA occurs when the ductus arteriosus blood vessel in the heart fails to close normally after birth, and indomethacin causes the vessel to close.

Side Effects and Drug Interactions

Common side effects of indomethacin include4:

  • Upset stomach
  • Heartburn
  • Headache
  • Drowsiness
  • Dizziness
  • Constipation or diarrhea
  • Gas or bloating
  • Rectal irritation
  • Skin rash
  • Blurred vision

Patients should contact a doctor immediately if they experience uncommon but serious side effects, including:

  • Swelling of the hands or feet (edema)
  • Sudden weight gain
  • Ringing in the ears
  • Uncontrollable mood changes
  • Difficulty swallowing
  • Severe fatigue
  • Neck stiffness
  • Changes in the amount of urine

In some cases, prolonged indomethacin use can cause peptic ulcers or severe liver disease, and it can worsen the symptoms of Parkinson’s disease, epilepsy, and psychotic disorders. Indomethacin also puts patients at significantly higher cardiovascular risk than other NSAIDs.5  

Indomethacin is known to interact with ACE-inhibitors and angiotensin II antagonists, aspirin, beta-adrenoceptor blocking agents, cyclosporine, diflunisal, digoxin, lithium, methotrexate, and probenecid. It may also reduce the effectiveness of potassium-sparing and thiazide diuretics. It should not be taken in conjunction with other NSAIDs.6  

Latest News and Research

Indomethacin was discovered in 1963 and approved for use by the FDA in 1965. Because it was one of the first NSAIDs to be discovered, indomethacin was used in the early biochemical research that revealed the mechanisms of NSAID action and the physiological importance of prostaglandins.7  

There is ongoing research into how indomethacin can be used to treat more conditions.

One recent study suggests that NSAID-metal ion complexes may be toxic to cancer cells that resist chemotherapy treatment. The combination of indomethacin with ruthenium and osmium ions was found to be more effective against ovarian cancer cells than cisplatin.8 Other studies seek to optimize the use of indomethacin as a tocolytic agent. The drug has been shown to effectively delay preterm labor, but it can cross the placental barrier and cause heart problems in the fetus. Some researchers are seeking to use nanoparticles to target indomethacin to the uterus in order to eliminate this risk.9

Safety concerns about indomethacin also continue to generate research. Indomethacin has a wide range of side effects and recent research highlights the drug’s ability to alter the activity of cell membrane proteins as a possible cause.10 Another study suggests that indomethacin could alter the composition of the gut microbiome, which can contribute to a wide range of health conditions, including metabolic disorders and depression.11

Buying Guide

Many compound pharmacists prefer other NSAIDs, including Diclofenac Sodium, Flurbiprofen, Ketoprofen,  Meloxicam, and Piroxicam, which can treat similar conditions but have less serious side effects. Please find more information about our Bulk APIs here.

Show 11 footnotes

  1. “Effect of antiinflammatory drugs COX-1 and COX-2 activity in human articular chondrocytes,” June 26, 1999, http://www.ncbi.nlm.nih.gov/pubmed/10381057
  2. “Effects of ketoprofen and indomethacin on leukocyte migration in two models of pleurisy induced by carrageenan or zymosan-activated serum in rats,” January 1989, http://www.ncbi.nlm.nih.gov/pubmed/2913275
  3. “Indomethacin,” March 1, 2016, http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0000945/
  4. “Indocin Side Effects Center,” April 24, 2015, http://www.rxlist.com/indocin-side-effects-drug-center.htm
  5. “Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies,” September 27, 2011, http://www.ncbi.nlm.nih.gov/pubmed/21980265
  6. “Drug Interactions,” July 11, 2007, http://www.rxlist.com/indocin-drug/side-effects-interactions.htm
  7. “The discovery of indomethacin and the proliferation of NSAIDs,” November 1982, http://www.semarthritisrheumatism.com/article/0049-0172(82)90004-X/abstract
  8. “Pairing pain medicine with metal ions to battle cancer,” February 17, 2016, http://www.acs.org/content/acs/en/pressroom/presspacs/2016/acs-presspac-february-17-2016/pairing-pain-medicine-with-metal-ions-to-battle-cancer.html
  9. “New Research Uses Nanotechnology to Prevent Preterm Birth, March of Dimes honors abstract on prematurity at SMFM Annual Meeting,” February 4, 2016, http://www.smfmnewsroom.org/2016/02/new-research-uses-nanotechnology-to-prevent-preterm-birth-march-of-dimes-honors-abstract-on-prematurity-at-smfm-annual-meeting/
  10. “Three commonly used NSAIDs affect cell membranes, produce unwanted side effects,” August 22, 2014, http://www.news-medical.net/news/20140822/Three-commonly-used-NSAIDs-affect-cell-membranes-produce-unwanted-side-effects.aspx
  11. “Bidirectional interactions between indomethacin and the murine intestinal microbiota,” December 23, 2015, https://elifesciences.org/content/4/e08973