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Clinical data
Pronunciation /ɪndˈmɛtəsn/
Trade names Indocid, Indocin
AHFS/ Monograph
License data
  • AU: C
Routes of
Oral, rectal, IV, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability ~100% (oral), 80–90% (rectal)
Protein binding 99%[1]
Metabolism Hepatic
Biological half-life 2.6-11.2 hours (adults), 12-28 hours (infants)[1]
Excretion Renal (60%), fecal (33%)
CAS Number
PubChem CID
PDB ligand
ECHA InfoCard 100.000.170
Chemical and physical data
Formula C19H16ClNO4
Molar mass 357.787 g.mol−1
3D model (Jmol)

Indometacin (INN and BAN) or indomethacin (AAN, USAN and former BAN) is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. It works by inhibiting the production of prostaglandins, molecules known to cause these symptoms.[1][2]

It is marketed under more than twelve different trade names.[3] As of 2015 the cost for a typical month of medication in the United States is less than 25 USD.[4]

Medical uses[edit]

Clinical indications for indometacin include:

Indometacin has also been used clinically to delay premature labor, reduce amniotic fluid in polyhydramnios, and to close patent ductus arteriosus.

Indometacin is a potent drug with many serious side effects and should not be considered an analgesic for minor aches and pains or fever. The medication is better described as an anti-inflammatory, rather than an analgesic. Indometacin can also affect warfarin and subsequently raise INR.


Adverse effects[edit]

In general, adverse effects seen with indomethacin are similar to all other NSAIDs. For instance, indometacin inhibits both cyclooxygenase-1 and cyclooxygenase-2, it inhibits the production of prostaglandins in the stomach and intestines, which maintain the mucous lining of the gastrointestinal tract. Indometacin, therefore, like other non-selective COX inhibitors can cause peptic ulcers. These ulcers can result in serious bleeding and/or perforation requiring hospitalization of the patient.

To reduce the possibility of peptic ulcers, indometacin should be prescribed at the lowest dosage needed to achieve a therapeutic effect, usually between 50–200 mg/day. It should always be taken with food. Nearly all patients benefit from an ulcer protective drug (e.g. highly dosed antacids, ranitidine 150 mg at bedtime, or omeprazole 20 mg at bedtime). Other common gastrointestinal complaints, including dyspepsia, heartburn and mild diarrhea are less serious and rarely require discontinuation of indometacin.

Many NSAIDs, but particularly indometacin, cause lithium retention by reducing its excretion by the kidneys. Thus indometacin users have an elevated risk of lithium toxicity. For patients taking lithium (e.g. for treatment of depression or bipolar disorder), less toxic NSAIDs such as sulindac or aspirin are preferred.

All NSAIDs, including indometacin, also increase plasma renin activity and aldosterone levels, and increase sodium and potassium retention. Vasopressin activity is also enhanced. Together these may lead to:

Elevations of serum creatinine and more serious renal damage such as acute renal failure, chronic nephritis and nephrotic syndrome, are also possible. These conditions also often begin with edema and hyperkalemia.

Paradoxically yet uncommonly, indometacin can cause headache (10 to 20%), sometimes with vertigo and dizziness, hearing loss, tinnitus, blurred vision (with or without retinal damage). There are unsubstantiated reports of worsening Parkinson's disease, epilepsy, and psychiatric disorders. Cases of life-threatening shock (including angioedema, sweating, severe hypotension and tachycardia as well as acute bronchospasm), severe or lethal hepatitis and severe bone marrow damage have all been reported. Skin reactions and photosensitivity are also possible side effects.

The frequency and severity of side effects and the availability of better tolerated alternatives make indometacin today a drug of second choice. Its use in acute gout attacks and in dysmenorrhea is well-established because in these indications the duration of treatment is limited to a few days only, therefore serious side effects are not likely to occur.

People should undergo regular physical examination to detect edema and signs of central nervous side effects. Blood pressure checks will reveal development of hypertension. Periodic serum electrolyte (sodium, potassium, chloride) measurements, complete blood cell counts and assessment of liver enzymes as well as of creatinine (renal function) should be performed. This is particularly important if Indometacin is given together with an ACE inhibitor or with potassium-sparing diuretics, because these combinations can lead to hyperkalemia and/or serious kidney failure. No examinations are necessary if only the topical preparations (spray or gel) are applied.

In women who are pregnant, it has been shown that use of this medication can have an effect of the fetal (Baby's) heart possibly resulting in fetal death via premature closing of the Ductus arteriosus; this is rare.[13]


Indometacin has a high acute toxicity both for animals (in rats, 12 mg/kg) and for humans. Exact human data does not exist, but some fatal human cases, particularly in children and adolescents, have been seen.

Generally, overdose in humans causes drowsiness, dizziness, severe headache, mental confusion, paresthesia, numbness of limbs, nausea and vomiting. Severe gastrointestinal bleeding is also possible. Cerebral edema, and cardiac arrest with fatal outcome have been seen in children.

The treatment is symptomatic and largely the same as with diclofenac. However, the possibility of severe GI tract symptoms should be particularly noted.

The risk of overdose after exaggerated local treatment with gel or spray is very limited.

Mechanism of action[edit]

Indometacin is a nonselective inhibitor of cyclooxygenase (COX) 1 and 2, enzymes that participate in prostaglandin synthesis from arachidonic acid. Prostaglandins are hormone-like molecules normally found in the body, where they have a wide variety of effects, some of which lead to pain, fever, and inflammation.

Indometacin has three additional modes of actions with clinical importance:

  • it inhibits motility of polymorphonuclear leukocytes, similar to colchicine
  • it uncouples oxidative phosphorylation in cartilaginous (and hepatic) mitochondria, like salicylates
  • decreased cerebral blood flow (see below)

Indometacin's role in treating certain headaches is unique compared to other NSAIDs. In addition to the class effect of COX inhibition, there is evidence that indometacin has the ability to alter cerebral blood flow not only through modulation of nitric oxide pathways but also via intracranial precapillary vasoconstriction.[14] This may be responsible for the remarkable efficacy in a group of headaches that is referred to as "indometacin-responsive headaches", such as idiopathic stabbing headache, chronic paroxysmal hemicranial, and exertional headaches.[15]

Prostaglandins also cause uterine contractions in pregnant women. Indometacin is an effective tocolytic agent,[16] able to delay premature labor by reducing uterine contractions through inhibition of prostaglandin synthesis in the uterus and possibly through calcium channel blockade.

Indometacin readily crosses the placenta and can reduce fetal urine production to treat polyhydramnios. It does so by reducing renal blood flow and increasing renal vascular resistance, possibly by enhancing the effects of vasopressin on the fetal kidneys.


Indometacin was discovered in 1963[17] and it was first approved for use in the U.S. by the Food and Drug Administration in 1965. Its mechanism of action, along with several other NSAIDs that inhibit COX, was described in 1971.[18]

See also[edit]


  1. ^ a b c Brayfield, A, ed. (14 January 2014). "Indometacin". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 22 June 2014. 
  2. ^ "TGA Approved Terminology for Medicines, Section 1 – Chemical Substances" (PDF). Therapeutic Goods Administration, Department of Health and Ageing, Australian Government. July 1999: 70. 
  3. ^ Trade names are listed on entry DB00328
  4. ^ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 8. ISBN 9781284057560. 
  5. ^ Sanders, Lisa (6 January 2012). "Think Like a Doctor: Ice Pick Pain Solved!". The New York Times. 
  6. ^ Garza, I & Schwedt, TJ. "Hemicrania continua." UpToDate. Accessed 8/27/13.
  7. ^ "Hemicrania Continua". The Migraine Trust. Retrieved 11 June 2014. 
  8. ^ a b c d Dodick, D.W. (8 February 2004). "Indomethacin-responsive headache syndromes". Current pain and headache reports. 8 (1): 19–26. doi:10.1007/s11916-004-0036-6. PMID 14731379. 
  9. ^ "Medication for Migraine". The Migraine Trust. Retrieved 11 June 2014. 
  10. ^ Smyth JM, Collier PS, Darwish M, et al. (September 2004). "Intravenous indometacin in preterm infants with symptomatic patent ductus arteriosus. A population pharmacokinetic study". Br J Clin Pharmacol. 58 (3): 249–58. doi:10.1111/j.1365-2125.2004.02139.x. PMC 1884560Freely accessible. PMID 15327584. 
  11. ^ "INDOMETHACIN". Hazardous Substances Data Bank (HSDB). National Library of Medicine's TOXNET. Retrieved April 4, 2013. 
  12. ^ Akbarpour F, Afrasiabi A, Vaziri N; Afrasiabi; Vaziri (1985). "Severe hyperkalemia caused by indomethacin and potassium supplementation". South Med J. 78 (6): 756–7. doi:10.1097/00007611-198506000-00039. PMID 4002013. 
  13. ^ Enzensberger, Christian; Wienhard, Julia; Weichert, Jan; Kawecki, Andreea; Degenhardt, Jan; Vogel, Melanie; Axt-Fliedner, Roland (2012-08-01). "Idiopathic Constriction of the Fetal Ductus Arteriosus Three Cases and Review of the Literature". Journal of Ultrasound in Medicine. 31 (8): 1285–1291. ISSN 0278-4297. PMID 22837295. 
  14. ^ AE Castellano, G Micieli, P Bellantonio, MG Buzzi, S Marcheselli, F Pompeo, F Rossi, G Nappi. Indomethacin Increases the Effect of Isosorbide Dinitrate on Cerebral Hemodynamic in Migraine Patients: Pathogenetic and Therapeutic Implications
  15. ^ John A. Yagiela, Frank J. Dowd, Bart Johnson, Angelo Mariotti, Enid A. Neidle. Pharmacology and Therapeutics for Dentistry. Chapter 23, Drugs for Treating Orofacial Pain Syndromes. 384-385
  16. ^ Giles W, Bisits A; Bisits (October 2007). "Preterm labour. The present and future of tocolysis". Best Pract Res Clin Obstet Gynaecol. 21 (5): 857–68. doi:10.1016/j.bpobgyn.2007.03.011. PMID 17459777. 
  17. ^ Hart F, Boardman P; Boardman (October 1963). "Indomethacin: A New Non-steroid Anti-inflammatory Agent". Br Med J. 2 (5363): 965–70. doi:10.1136/bmj.2.5363.965. PMC 1873102Freely accessible. PMID 14056924. 
  18. ^ Ferreira S, Moncada S, Vane J; Moncada; Vane (Jun 23, 1971). "Indomethacin and aspirin abolish prostaglandin release from the spleen". Nat New Biol. 231 (25): 237–9. doi:10.1038/newbio231237a0. PMID 5284362. 

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