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. ==Pharmacology==