Since 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.
Indometacin also increases plasma renin activity and aldosterone levels, and increases sodium and potassium retention. It also enhances the effects of vasopressin. Together these may lead to:
edema (swelling due to fluid retention)
hyperkalemia (high potassium levels)[12]
hypernatremia (high sodium levels)
hypertension
The drug may also cause elevations of serum creatinine and more serious renal damage such as acute renal failure, chronic nephritis and nephrotic syndrome. These conditions also often begin with edema and hyperkalemia.
Additionally, indometacin quite often causes headache (10 to 20%), sometimes with vertigo and dizziness, hearing loss, tinnitus, blurred vision (with or without retinal damage). There were reports of worsening Parkinson's disease, epilepsy, and psychiatric disorders but these are not substantiated. 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.
Due to its strong antipyretic activity indometacin may obscure the clinical course of serious infections.
Psychosis has also been reported with prolonged use.
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.
