Indometacin, also known as indomethacin, 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, endogenous signaling molecules known to cause these symptoms. It does this by inhibiting cyclooxygenase, an enzyme that catalyzes the production of prostaglandins. It was patented in 1961 and approved for medical use in 1963. It is on the World Health Organization's List of Essential Medicines. In 2023, it was the 287th most commonly prescribed medication in the United States, with more than 500,000 prescriptions.
Medical uses As an NSAID, indometacin is an analgesic, anti-inflammatory, and antipyretic. Clinical indications for indometacin include: Joint diseases
rheumatoid arthritis ankylosing spondylitis osteoarthritis gouty arthritis acute painful shoulder bursitis or tendinitis Headaches
Trigeminal autonomic cephalgias Paroxysmal hemicranias Chronic paroxysmal hemicrania Episodic paroxysmal hemicrania Hemicrania continua Valsalva-induced headaches Primary cough headache Primary exertional headache Primary headache associated with sexual activity (preorgasmic and orgasmic) Primary stabbing headache (jabs and jolts syndrome) Hypnic headache Others
Patent ductus arteriosus
Contraindications Concurrent peptic ulcer, or history of ulcer disease Allergy to indometacin, aspirin, or other NSAIDs Roux-en-Y gastric bypass and gastric sleeve patients Patients with nasal polyps reacting with an angioedema to other NSAIDs Children under 2 years of age (with the exception of neonates with patent ductus arteriosus) Severe pre-existing renal and liver damage Caution: pre-existing bone marrow damage (frequent blood cell counts are indicated) Caution: bleeding tendencies of unknown origin (indometacin inhibits platelet aggregation) Caution: Parkinson's disease, epilepsy, psychotic disorders (indometacin may worsen these conditions) Concurrent with potassium sparing diuretics Patients who have a patent ductus arteriosus dependent heart defect (such as transposition of the great vessels) Significant hypertension (high blood pressure) Concomitant administration of lithium salts (such as lithium carbonate)
Adverse effects
In general, the adverse effects of indometacin are similar to those of all other NSAIDs. For instance, indometacin inhibits both cyclooxygenase-1 and cyclooxygenase-2, which then inhibits the production of prostaglandins in the stomach and intestines responsible for maintaining 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 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 and 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:
Edema (swelling due to fluid retention) Hyperkalemia (high potassium levels) Hypernatremia (high sodium levels) Hypertension Elevations of serum creatinine and more serious renal damage such as acute kidney failure, chronic nephritis and nephrotic syndrome, are also possible. These conditions also often begin with edema and high potassium levels in the blood. 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. Rare cases have shown that use of this medication by pregnant women can have an effect on the fetal heart, possibly resulting in fetal death via premature closing of the Ductus arteriosus. In October 2020, the U.S. Food and Drug Administration (FDA) required the prescribing information to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid. They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.
Pharmacology
Mechanism of action
… excerpt ends here. Continue reading the full article.
