Description

Simple

A painkiller medication used to treat various types of pain in adults, as well as for the reversal of heart defects in premature infants.

Clinical

A nonsteroidal anti-inflammatory (NSAID) used for symptomatic management of chronic musculoskeletal pain conditions and to induce closure of a hemodynamically significant patent ductus arteriosus in premature infants.

Overview

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.[1] 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, [10] along with other acetic acid derivatives such as [diclofenac] and [sulindac] that were also developed during the 1960s.[Read more

Pharmacology

Indication

Oral indometacin is indicated for symptomatic management of moderate to severe rheumatoid arthritis including acute flares of chronic disease, moderate to severe ankylosing spondylitis, moderate to severe osteoarthritis, acute painful shoulder (bursitis and/or tendinitis) and acute gouty arthritis.[... Read more

Pharmacodynamic

Indometacin is an NSAID with analgesic and antipyretic properties that exerts its pharmacological effects by inhibiting the synthesis of factors involved in pain, fever, and inflammation. Its therapeutic action does not involve pituitary-adrenal stimulation.[ Read more

Mechanism of action

Indometacin is a nonspecific and reversible inhibitor of the cyclo-oxygenase (COX) enzyme, or prostaglandin G/H synthase. There are two identified isoforms of COX: COX-1 is universally present in most body tissues and is involved in the synthesis of the prostaglandins and thromboxane A2, while COX-2... Read more

Absorption

Indometacin displays a linear pharmacokinetics profile where the plasma concentrations and area under the curve (AUC) are dose-proportional, whereas half-life (T1/2) and plasma and renal clearance are dose-dependent.[ Read more

Protein binding

Indometacin is a weak organic acid that is 90-99% bound to protein in plasma over the expected range of therapeutic plasma concentrations [ Read more

Volume of distribution

The volume of distribution ranged from 0.34 to 1.57 L/kg following oral, intravenous, or rectal administration of single and multiple doses of indometacin in healthy individuals.[ Read more

Clearance

In a clinical pharmacokinetic study, the plasma clearance of indometacin was reported to range from 1 to 2.5 mL/kg/min following oral administration.[ Read more

Half life

Indometacin disposition from the plasma is reported to be biphasic, with a half-life of 1 hour during the initial phase and 2.6–11.2 hours during the second phase.[ Read more

Route of elimination

Indometacin is eliminated via renal excretion, metabolism, and biliary excretion. It is also subject to enter the enterohepatic circulation through excretion of its glucuronide metabolites into bile followed by resorption of indometacin after hydrolysis [ Read more

Toxicity

Acute oral LD50 is 2.42 mg/kg in rats and 13 mg/kg in mice.[MSDS] The oral LD50 of indomethacin in mice and rats (based on 14-day mortality response) was 50 and 12 mg/kg, respectively.[11]

Symp... Read more

Adverse Effects

Contraindications

  • Route:
    • Intravenous
  • Regions: US
  • Age Groups:
    • neonatal
    • premature infants
  • Patient Conditions:
      • Name: Patent Ductus Arteriosus
      • Drugbank Id: DBCOND0031877
      • Name: Neonatal Congenital Heart Disease
      • Drugbank Id: DBCOND0043939
  • Patient Conditions Associated With:
      • Name: Aortic Coarctation
      • Drugbank Id: DBCOND0000541
      • Name: Tetralogy Of Fallot
      • Drugbank Id: DBCOND0065153
      • Name: Pulmonary Atresia
      • Drugbank Id: DBCOND0000569
      • Name: Reduction of Blood Flow
      • Drugbank Id: DBCOND0077897
  • Route:
    • Intravenous
  • Regions: US
  • Age Groups:
    • neonatal
    • premature infants
  • Patient Conditions:
      • Name: Renal Impairment
      • Drugbank Id: DBCOND0031781
  • Route:
    • Intravenous
  • Regions: US
  • Age Groups:
    • neonatal
    • premature infants
  • Patient Conditions:
      • Name: Suspected necrotizing enterocolitis
      • Drugbank Id: DBCOND0107642
  • Route:
    • Intravenous
  • Regions: US
  • Age Groups:
    • neonatal
    • premature infants
  • Patient Conditions:
      • Name: Coagulation Defects
      • Drugbank Id: DBCOND0057558
  • Route:
    • Intravenous
  • Regions: US
  • Age Groups:
    • neonatal
    • premature infants
  • Patient Conditions:
      • Name: Thrombocytopenia
      • Drugbank Id: DBCOND0006608
  • Route:
    • Intravenous
  • Regions: US
  • Age Groups:
    • neonatal
    • premature infants
  • Patient Conditions:
      • Name: Intracranial Haemorrhage
      • Drugbank Id: DBCOND0086527
      • Name: Bleeding
      • Drugbank Id: DBCOND0020313
      • Name: Gastrointestinal haemorrhage
      • Drugbank Id: DBCOND0011340
  • Route:
    • Intravenous
  • Regions: US
  • Age Groups:
    • neonatal
    • premature infants
  • Patient Conditions:
      • Name: Proven or suspected untreated infection
      • Drugbank Id: DBCOND0107641
  • Hypersensitivity:
    • true
  • Sex Group: all
  • Regions: US
  • Route:
    • Oral
    • Rectal
  • Regions: US
  • Patient Conditions:
      • Name: History of allergic reaction caused by Anti-Inflammatory Agents, Non-Steroidal
      • Drugbank Id: DBCOND0107640
      • Combination Of:
        • Caused By:
            • Name: Anti-Inflammatory Agents, Non-Steroidal
            • Drugbank Id: DBCOND0052889
        • Included Conditions:
            • Name: History of allergic reaction
            • Drugbank Id: DBCOND0107639
  • Route:
    • Oral
    • Rectal
  • Regions: US
  • Patient Conditions:
      • Name: History of urticaria caused by Anti-Inflammatory Agents, Non-Steroidal
      • Drugbank Id: DBCOND0107638
      • Combination Of:
        • Caused By:
            • Name: Anti-Inflammatory Agents, Non-Steroidal
            • Drugbank Id: DBCOND0052889
        • Included Conditions:
            • Name: History of urticaria
            • Drugbank Id: DBCOND0107637
  • Route:
    • Oral
    • Rectal
  • Regions: US
  • Patient Conditions:
      • Name: History of asthma caused by Anti-Inflammatory Agents, Non-Steroidal
      • Drugbank Id: DBCOND0107636
      • Combination Of:
        • Caused By:
            • Name: Anti-Inflammatory Agents, Non-Steroidal
            • Drugbank Id: DBCOND0052889
        • Included Conditions:
            • Name: History of asthma
            • Drugbank Id: DBCOND0107635
  • Route:
    • Oral
    • Rectal
  • Regions: US
  • With Therapies:
      • Name: Coronary Artery Bypass Graft Surgery
      • Drugbank Id: DBCOND0032060

Food Interactions

  • Avoid alcohol.
  • Take with or without food. Food has no effect on drug absorption. However, food may decrease the extent of gastrointestinal irritation caused by indomethacin.

Interactions

Type in a drug name to check for interaction with Indomethacin
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The risk or severity of bleeding and hemorrhage can be increased when Indomethacin is combined with (R)-warfarin.
(S)-Warfarin
The risk or severity of bleeding and hemorrhage can be increased when Indomethacin is combined with (S)-Warfarin.
1-benzylimidazole
The risk or severity of hypertension can be increased when Indomethacin is combined with 1-benzylimidazole.
2-Methoxyethanol
The risk or severity of adverse effects can be increased when Indomethacin is combined with 2-Methoxyethanol.
2,4-thiazolidinedione
The risk or severity of hypoglycemia can be increased when Indomethacin is combined with 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamine
The risk or severity of hypertension can be increased when Indomethacin is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine
The risk or severity of hypertension can be increased when Indomethacin is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamine
The risk or severity of hypertension can be increased when Indomethacin is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarin
The risk or severity of bleeding and hemorrhage can be increased when Indomethacin is combined with 4-hydroxycoumarin.
4-Methoxyamphetamine
The risk or severity of hypertension can be increased when Indomethacin is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine
The risk or severity of hypertension can be increased when Indomethacin is combined with 5-methoxy-N,N-dimethyltryptamine.
9-(N-methyl-L-isoleucine)-cyclosporin A
The risk or severity of adverse effects can be increased when Indomethacin is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
Abacavir
Indomethacin may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abatacept
The metabolism of Indomethacin can be increased when combined with Abatacept.
Abciximab
The risk or severity of bleeding and hemorrhage can be increased when Indomethacin is combined with Abciximab.
Abediterol
The risk or severity of hypertension can be increased when Indomethacin is combined with Abediterol.
Abemaciclib
The serum concentration of Abemaciclib can be increased when it is combined with Indomethacin.
Abetimus
The risk or severity of adverse effects can be increased when Indomethacin is combined with Abetimus.
Abiraterone
The metabolism of Indomethacin can be decreased when combined with Abiraterone.
Acarbose
Indomethacin may decrease the excretion rate of Acarbose which could result in a higher serum level.
12 References
  1. 1 . Lucas S: The Pharmacology of Indomethacin. Headache. 2016 Feb;56(2):436-46. doi: 10.1111/head.12769. Epub 2016 Feb 11.PubMed: 26865183
  2. 2 . Helleberg L: Clinical Pharmacokinetics of indomethacin. Clin Pharmacokinet. 1981 Jul-Aug;6(4):245-58. doi: 10.2165/00003088-198106040-00001.PubMed: 7249487
  3. 3 . Nalamachu S, Wortmann R: Role of indomethacin in acute pain and inflammation management: a review of the literature. Postgrad Med. 2014 Jul;126(4):92-7. doi: 10.3810/pgm.2014.07.2787.PubMed: 25141247
  4. 4 . Pacifici GM: Clinical pharmacology of indomethacin in preterm infants: implications in patent ductus arteriosus closure. Paediatr Drugs. 2013 Oct;15(5):363-76. doi: 10.1007/s40272-013-0031-7.PubMed: 23754139
  5. 5 . Jensen KM, Grenabo L: Bioavailability of indomethacin after intramuscular injection and rectal administration of solution and suppositories. Acta Pharmacol Toxicol (Copenh). 1985 Nov;57(5):322-7.PubMed: 4090993
  6. 6 . 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: 22970738
  7. 7 . Alvan G, Orme M, Bertilsson L, Ekstrand R, Palmer L: Pharmacokinetics of indomethacin. Clin Pharmacol Ther. 1975 Sep;18(3):364-73.PubMed: 1100305
  8. 8 . Ricciotti E, FitzGerald GA: Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011 May;31(5):986-1000. doi: 10.1161/ATVBAHA.110.207449.PubMed: 21508345
  9. 9 . Rouzer CA, Marnett LJ: Cyclooxygenases: structural and functional insights. J Lipid Res. 2009 Apr;50 Suppl:S29-34. doi: 10.1194/jlr.R800042-JLR200. Epub 2008 Oct 23.PubMed: 18952571
  10. 10 . HART FD, BOARDMAN PL: INDOMETHACIN: A NEW NON-STEROID ANTI-INFLAMMATORY AGENT. Br Med J. 1963 Oct 19;2(5363):965-70.PubMed: 14056924
  11. 11 . Indomethacin Capsules (25 mg) - FDA Label Link
  12. 12 . Indocin I.V. (indomethacin for injection) - FDA Label Link