Indomethacin capsules are indicated for:

• 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)
• Acute gouty arthritis

Adverse reactions generally appear to correlate with the dose of indomethacin. Therefore, every effort should be made to determine the lowest effective dosage for the individual patient.

Safety and effectiveness in pediatric patients 14 years of age and younger have not been established. Indomethacin capsules should not be prescribed for pediatric patients 14 years of age and younger unless toxicity or lack of efficacy associated with other drugs warrants the risk.

Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects.

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.

Indomethacin capsules are contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

Strategies to Minimize the GI Risks in NSAID-treated patients:

• Use the lowest effective dosage for the shortest possible duration
• Avoid administration of more than one NSAID at a time
• Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs
• Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy
• If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue indomethacin capsules until a serious GI adverse event is ruled out
• In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding

Elevations of ALT or AST (three or more times the upper limit of normal [ULN]) have been reported in approximately 1% of NSAID-treated patients in clinical trials. In addition, rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure have been reported.

NSAIDs, including indomethacin capsules, can lead to new onset of hypertension or worsening of pre existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs.

The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.

Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs.

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.

Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state.

Indomethacin capsules may aggravate depression or other psychiatric disturbances, epilepsy, and parkinsonism, and should be used with considerable caution in patients with these conditions.

Corneal deposits and retinal disturbances, including those of the macula, have been observed in some patients who had received prolonged therapy with indomethacin capsules.

NSAIDs, including indomethacin capsules, may increase the risk of bleeding events. Comorbid conditions, such as coagulation disorders, or concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk.

Indomethacin has been associated with anaphylactic reactions in patients with and without known hypersensitivity to indomethacin and in patients with aspirin-sensitive asthma.

A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs

NSAIDs, including indomethacin, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as indomethacin capsules. Some of these events have been fatal or life-threatening.

Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis

Indomethacin capsules are not a substitute for low dose aspirin for cardiovascular protection.

Indomethacin and triamterene should not be administered together.

Both indomethacin and potassium-sparing diuretics may be associated with increased serum potassium levels. The potential effects of indomethacin and potassium-sparing diuretics on potassium levels and renal function should be considered when these agents are administered concurrently.

Indomethacin and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of indomethacin and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone.

Concomitant use of indomethacin capsules and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding.

NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol). In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure.

The concomitant use of indomethacin with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin.

NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance.

Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction).

Concomitant use of indomethacin capsules and cyclosporine may increase cyclosporine’s nephrotoxicity.

Concomitant use of indomethacin with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy. Combined use with diflunisal may be particularly hazardous because diflunisal causes significantly higher plasma levels of indomethacin. In some patients, combined use of indomethacin and diflunisal has been associated with fatal gastrointestinal hemorrhage.
The concomitant use of indomethacin with other NSAIDs or salicylates, especially diflunisal, is not recommended.

Concomitant use of indomethacin capsules and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity.

When indomethacin is given to patients receiving probenecid, the plasma levels of indomethacin are likely to be increased.

Indomethacin capsules reduce basal plasma renin activity (PRA), as well as those elevations of PRA  induced by furosemide administration, or salt or volume depletion. These facts should be considered when evaluating plasma renin activity in hypertensive patients.

False-negative results in the dexamethasone suppression test (DST) in patients being treated with
indomethacin have been reported. Thus, results of the DST should be interpreted with caution in these patients.

Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including indomethacin capsules, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women.

Avoid use of NSAIDs, including indomethacin capsules, in pregnant women at about 30 weeks gestation and later. NSAIDs, including indomethacin capsules, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age.

Use of NSAIDs, including indomethacin capsules, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.

Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment.

If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit indomethacin capsules use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring for amniotic fluid if indomethacin capsules treatment extends beyond 48 hours. Discontinue indomethacin capsules if oligohydramnios occurs and follow up according to clinical practice.

Based on available published clinical data, indomethacin may be present in human milk.

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• Use in patients under 14 years of age. GoToSource

• Reduce cognitive decline in patients with mild to moderately impaired alzheimer’s disease. GoToSource

• Headaches. GoToSource

• Chronic back pain. GoToSource

• Menstrual cramps. GoToSource

• Inhibition of premature labor. GoToSource

Anaphylaxis (potentially life-threatening allergic reaction), urticaria (hives), angioedema (swelling in deep layers of skin), peptic ulcers, tinnitus (ringing or buzzing in ears), vertigo (sensation of motion or spinning), depression, interstitial nephritis (kidney disorder), agranulocytosis (low number of granulocytes in blood, a type of white blood cell), aplastic anemia (body fails to produce blood cells in sufficient numbers), hemolytic anemia (red blood cells are destroyed faster than they can be replaced), leukopenia (low white blood cell count), thrombocytopenia (low blood platelet count), thrombocytopenic purpura (platelets are destroyed by the immune system), respiratory distress, pulmonary edema and congestive heart failure. GoToSource

Bleeding, ulcerations or perforation of the stomach or intestines. GoToSource

Liver injury and failure. GoToSource

Hypertension (high blood pressure). GoToSource

Kidney failure. GoToSource

Hyperkalemia (high blood potassium level). GoToSource

Ischemic stroke. GoToSource

Cognitive dysfunction, depression depersonalisation, hallucination and psychosis. GoToSource

Retinopathy (disease of the retina), color vision defects, retinal pigmentation and thinning and macular edema. GoToSource

Drug rash with eosinophilia and systemic symptoms syndrome (severe skin disorder). GoToSource

Lawsuits filed for pancreatitis, heart attacks, strokes and ulcer or stomach perforation.