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Indocin

Pronunciation

Generic Name: Indomethacin
Class: Other Nonsteroidal Anti-inflammatory Agents
CAS Number: 53-86-1

For Professionals Side Effects Interactions More...

Warning(s)

Cardiovascular Risk
Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).⁴²⁰ Risk may increase with duration of use.⁴²⁰ Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.⁴²⁰ (See Cardiovascular Effects under Cautions.)
Contraindicated for the treatment of pain in the setting of CABG surgery.⁴²⁰

GI Risk
Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).⁴²⁰ Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.⁴²⁰ Geriatric individuals are at greater risk for serious GI events.⁴²⁰ (See GI Effects under Cautions.)

Introduction

Prototypical NSAIA; indoleacetic acetic acid derivative.³⁰¹ ³⁴¹ ⁴²⁰

Uses for Indocin

When used for inflammatory diseases, consider potential benefits and risks of indomethacin therapy as well as alternative therapies before initiating therapy with the drug.⁴²⁰ Use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.⁴²⁰

Inflammatory Diseases

Symptomatic treatment of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis.³⁴¹ ⁴²⁰

Symptomatic relief of acute gout and acute painful shoulder (i.e., bursitis and/or tendinitis).³⁴¹ ⁴²⁰

Management of juvenile rheumatoid arthritis† in children ≥2 years of age.⁴²⁰

Patent Ductus Arteriosus (PDA)

Treatment of PDA in premature neonates.³⁰¹ ³⁰² ³⁰³ ³⁰⁴ ³⁰⁵ ³⁰⁶ ³⁰⁸ ³⁰⁹ ³¹⁰ ³¹¹ ³¹² ³¹³ ³¹⁴ ³¹⁶ ³¹⁸ ³¹⁹ ³²⁰ ³²² ³²³ ³²⁴ ³²⁵ ³²⁶ Used to promote closure of a hemodynamically significant PDA (i.e., left-to-right shunt large enough to compromise cardiorespiratory status) in premature neonates weighing 500–1750 g when 36–48 hours of usual medical management (e.g., fluid restriction, diuretics, cardiac glycosides, respiratory support) is ineffective.³⁰¹ ³⁰⁶ ³⁰⁷ ³¹³

Pericarditis

Reduction of pain, fever, and inflammation of pericarditis†;^a however, other drugs (i.e., aspirin) generally are preferred.⁴⁵²

Indocin Dosage and Administration

General

For inflammatory diseases, consider potential benefits and risks of indomethacin therapy as well as alternative therapies before initiating therapy with the drug.⁴²⁰

Administration

Administer orally or rectally (for inflammatory diseases or pericarditis)³⁴¹ ⁴²⁰ or by IV infusion (for PDA).³⁰¹

Oral Administration

In patients who have persistent night pain and/or morning stiffness, a large portion (maximum 100 mg) of the total daily dose may be given at bedtime.³⁴¹ ⁴²⁰

Conventional Capsules and Oral Suspension

Administer conventional capsules and oral suspension in 2–4 divided doses daily.⁴²⁰

Extended-release Capsules

Administer extended-release capsules once or twice daily.³⁴¹

Extended-release capsules can be used as an alternative to conventional capsules: 75 mg once daily (extended-release) as an alternative to 25 mg 3 times daily (conventional); 75 mg twice daily (extended-release) as an alternative to 50 mg 3 times daily (conventional).³⁴¹

Swallow extended-release capsules intact.³⁴¹

Extended-release capsules are not recommended for treatment of acute gouty arthritis.³⁴¹

Rectal Administration

Administer in 2–4 divided doses daily.⁴²⁰

Retain suppositories in rectum for ≥1 hour to ensure complete absorption.⁴²⁰

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion.³⁰¹

Avoid extravasation (irritating to extravascular tissues).³⁰¹

Reconstitution

Reconstitute vial containing 1 mg of indomethacin with 1 or 2 mL of preservative-free 0.9% sodium chloride injection or sterile water for injection to provide a solution containing 1 mg/mL or 0.5 mg/mL, respectively.³⁰¹ Further dilution is not recommended.³⁰¹

Use of bacteriostatic water for injection containing benzyl alcohol is not recommended because of potential risk of benzyl alcohol exposure if administered to a neonate.³⁰¹

Prepare solutions immediately before use; discard any unused solution.³⁰¹

Rate of Administration

Optimum rate not established; may administer dose over 20–30 minutes.³⁰¹

Dosage

Available as indomethacin and indomethacin sodium; dosage expressed in terms of indomethacin.³⁰¹ ³⁴¹ ⁴²⁰

To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.⁴²⁰ Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.⁴²⁰

Pediatric Patients

Inflammatory Diseases

Juvenile Rheumatoid Arthritis†

Oral

Children ≥2 years of age: Initially, 1–2 mg/kg daily in divided doses.³⁴¹ ⁴²⁰ Increase dosage until a satisfactory response is achieved, up to maximum dosage of 3 mg/kg daily or 150–200 mg daily (whichever is less) in divided doses; limited data support the use of a maximum dosage of 4 mg/kg daily or 150–200 mg daily (whichever is less) in divided doses.³⁴¹ ⁴²⁰ As symptoms subside, reduce dosage to the lowest effective level or discontinue the drug.³⁴¹ ⁴²⁰

PDA

IV

Each course of therapy consists of up to 3 doses administered at 12- to 24-hour intervals.³⁰¹

Base dosage on neonate’s age at the time therapy is initiated.³⁰¹

Dosage for the Management of PDA in Neonates
Age at First Dose	First Dose	Second Dose	Third Dose
<48 hours	0.2 mg/kg	0.1 mg/kg	0.1 mg/kg
2–7 days	0.2 mg/kg	0.2 mg/kg	0.2 mg/kg
>7 days	0.2 mg/kg	0.25 mg/kg	0.25 mg/kg

If anuria or oliguria (urine output <0.6 mL/kg per hour) is present at the time of a second or third dose, withhold the dose until laboratory determinations indicate that renal function has returned to normal.³⁰¹

If ductus arteriosus closes or is substantially constricted 48 hours or longer after completion of the first course, no further doses are necessary.³⁰¹

If ductus reopens, a second course of 1–3 doses may be administered.³⁰¹ Surgical ligation may be necessary if ductus is unresponsive to 2 courses of therapy.³⁰¹

Pericarditis†

Oral

50–100 mg daily in 2–4 divided doses.^a

Adults

Inflammatory Diseases

Osteoarthritis, Rheumatoid Arthritis, or Ankylosing Spondylitis

Oral

Conventional capsules or oral suspension: Initially, 25 mg 2 or 3 times daily.⁴²⁰ If needed, increase dosage by 25 or 50 mg daily at weekly intervals until a satisfactory response is obtained up to a maximum dosage of 150–200 mg daily.⁴²⁰

Extended-release capsules: Initially, 75 mg once daily.³⁴¹ May increase dosage to 75 mg twice daily.³⁴¹

Rectal

25 mg 2 or 3 times daily. If needed, increase dosage by 25 or 50 mg daily at weekly intervals until a satisfactory response is obtained up to a maximum dosage of 150–200 mg daily.⁴²⁰

Gout

Oral

Conventional capsules: 50 mg 3 times daily until pain is tolerable; then reduce dosage rapidly and discontinue.⁴²⁰

Painful Shoulder

Oral

Conventional capsules or oral suspension: 75–150 mg daily in 3 or 4 divided doses.⁴²⁰ Discontinue once symptoms have been controlled for several days; usual course of therapy is 7–14 days.⁴²⁰

Extended-release capsules: 75 mg once or twice daily.³⁴¹ Discontinue once symptoms have been controlled for several days; usual course of therapy is 7–14 days.³⁴¹

Rectal

75–150 mg daily in 3 or 4 divided doses.⁴²⁰ Discontinue once symptoms have been controlled for several days; usual course of therapy is 7–14 days.⁴²⁰

Pericarditis†

Oral

75–200 mg daily in 3 or 4 divided doses.^a

Prescribing Limits

Pediatric Patients

Juvenile Rheumatoid Arthritis

Oral

Maximum 4 mg/kg or 150–200 mg daily, whichever is less.⁴²⁰

Adults

Inflammatory Diseases

Rheumatoid Arthritis, Osteoarthritis, or Ankylosing Spondylitis

Oral

Maximum 200 mg daily.⁴²⁰

Rectal

Maximum 200 mg daily.⁴²⁰

Special Populations

Geriatric Patients

Careful dosage selection recommended due to possible age-related decreases in renal function.³⁴¹ ⁴²⁰

Cautions for Indocin

Contraindications

Known hypersensitivity to indomethacin or any ingredient in the formulation.³⁴¹ ⁴²⁰
History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.³⁴¹ ⁴²⁰
Treatment of perioperative pain in the setting of CABG surgery.⁴²⁰
When administered rectally, history of proctitis or recent rectal bleeding.⁴²⁰
When used for PDA, known or suspected untreated infection; bleeding, especially active intracranial hemorrhage or GI bleeding; thrombocytopenia; coagulation defects; known or suspected necrotizing enterocolitis; substantial renal impairment; congenital heart disease if patency of the ductus arteriosus is necessary for pulmonary or systemic blood flow (e.g., pulmonary atresia, severe tetralogy of Fallot, severe coarctation of the aorta).³⁰¹

Warnings/Precautions

Warnings

Cardiovascular Effects

Selective COX-2 inhibitors have been associated with an increased risk of cardiovascular events in certain situations.⁴⁸⁴ Several prototypical NSAIAs also have been associated with an increased risk of cardiovascular events.⁴⁸⁷ ⁴⁸⁸ ⁴⁸⁹ Current evidence suggests that use of indomethacin is associated with increased cardiovascular risk.⁴⁸⁷ ⁴⁸⁸ ⁴⁸⁹ ⁴⁹⁰

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events), and at the lowest effective dosage for the shortest duration necessary.⁴²⁰

Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).⁴⁸⁴

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.⁴²⁰ (See Specific Drugs under Interactions.)

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.⁴²⁰ Use with caution in patients with hypertension; monitor BP.⁴²⁰ Impaired response to certain diuretics may occur.⁴²⁰ (See Specific Drugs under Interactions.)

Fluid retention and edema reported.³⁴¹ ⁴²⁰ Caution in patients with fluid retention or heart failure.³⁴¹ ⁴²⁰

Deterioration of circulatory hemodynamics reported in patients with severe heart failure and hyponatremia.³⁴¹ ⁴²⁰

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.⁴²⁰

Incidence of major GI bleeding reported in neonates receiving IV indomethacin in clinical studies similar to that in neonates receiving placebo; minor GI bleeding occurred more frequently in indomethacin-treated neonates.³⁰¹

When used for inflammatory diseases in patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol;⁴⁵⁷ ⁴⁶⁴ alternatively, consider concomitant use of a proton-pump inhibitor (e.g., omeprazole)⁴⁵⁷ ⁴⁶⁴ or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).⁴⁶⁴

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.³⁴¹ ⁴²⁰

Potential for overt renal decompensation.³⁴¹ ⁴²⁰ Increased risk of renal toxicity in adults with renal or hepatic impairment or heart failure, in patients with volume depletion, in geriatric patients, and in those receiving a diuretic, ACE inhibitor, or angiotension II receptor antagonist.⁴²⁰ ⁴⁸⁶ (See Renal Impairment under Cautions.)

May precipitate renal insufficiency in neonates; increased risk in those with extracellular volume depletion, CHF, sepsis, or hepatic dysfunction or those receiving concomitant therapy with a nephrotoxic drug.³⁰¹ If a substantial reduction in urine output occurs, withhold additional doses until output returns to normal.³⁰¹ (See PDA under Dosage and Administration.)

Hyponatremia reported in neonates.³⁰¹ ³⁰² ³⁰³ ³⁰⁶ ³¹⁴ ³²⁴ ³²⁵ ³²⁶ ³²⁹ ³⁴⁸ ³⁷¹ Monitor renal function and serum electrolytes.³⁰¹

Hyperkalemia reported in adults.³⁴¹ ⁴²⁰

Hematologic Effects

Potential for spontaneous intraventricular hemorrhage in neonates.³⁰¹ Observe premature infants for signs of bleeding.³⁰¹

Contraindicated in neonates who are bleeding and in those with thrombocytopenia or coagulation defects.³⁰¹

Ocular Effects

Corneal deposits and retinal disturbances reported in patients receiving long-term therapy.³⁴¹ ⁴²⁰ Ophthalmic examination recommended in patients with blurred vision; periodic ophthalmic examinations recommended in patients receiving long-term therapy.³⁴¹ ⁴²⁰

CNS Effects

May aggravate depression or other psychiatric disturbances, epilepsy, or parkinsonism; use with caution in patients with these conditions.³⁴¹ ⁴²⁰

May cause drowsiness; may impair ability to perform activities requiring mental alertness.³⁴¹ ⁴²⁰

May cause headache.³⁴¹ ⁴²⁰ Discontinue the drug in patients in whom indomethacin-induced headache persists despite a reduction in dosage.³⁴¹ ⁴²⁰

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions (e.g., anaphylaxis, angioedema) reported.³⁴¹ ⁴²⁰

Immediate medical intervention and discontinuance for anaphylaxis.³⁴¹ ⁴²⁰

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.³⁴¹ ⁴²⁰

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.⁴²⁰ Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).⁴²⁰

General Precautions

Hepatic Effects

Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs.³⁴¹ ⁴²⁰

Elevations of serum ALT or AST reported.³⁴¹ ⁴²⁰

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.³⁴¹ ⁴²⁰ Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur or if liver function test abnormalities persist or worsen.³⁰¹ ³⁴¹ ⁴²⁰

Hematologic Precautions

Anemia reported rarely.⁴²⁰ Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.⁴²⁰

May inhibit platelet aggregation and prolong bleeding time.³⁴¹ ⁴²⁰ When used for inflammatory diseases, use with caution in patients with coagulation defects.³⁴¹ ⁴²⁰

Other Precautions

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.⁴²⁰

May mask certain signs of infection.³⁴⁰ ³⁴¹ ⁴²⁰

Obtain CBC and chemistry profile periodically during long-term use.⁴²⁰

Specific Populations

Pregnancy

Category C.⁴²⁰ Avoid use in third trimester because of possible premature closure of the ductus arteriosus.³⁴¹ ⁴²⁰

Lactation

Distributed into milk; use not recommended.³⁴¹ ⁴²⁰

Pediatric Use

Safety and efficacy established in neonates receiving the drug for PDA.³⁰¹

Safety and efficacy of oral or rectal indomethacin not established in children ≤14 years of age.³⁴¹ ⁴²⁰

Indomethacin should not be used in children 2–14 years of age unless toxicity or lack of efficacy with other drugs justifies the risk.⁴²⁰

Adverse effects reported in children receiving indomethacin capsules generally comparable to those reported in adults.⁴²⁰ Hepatotoxicity, sometimes fatal, has been reported in pediatric patients with juvenile rheumatoid arthritis.⁴²⁰ Periodic assessment of liver function recommended.⁴²⁰

Geriatric Use

Caution advised.⁴²⁰ Geriatric patients appear to tolerate NSAIA-induced adverse effects less well than younger individuals.³⁴¹ ⁴²⁰ Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.³⁴¹ ⁴²⁰

Possible confusion or, rarely, psychosis in geriatric patients.⁴²⁰

Substantially eliminated by the kidney; select dosage carefully and assess renal function periodically since geriatric patients more likely to have decreased renal function.³⁴¹ ⁴²⁰

Renal Impairment

Use not recommended in patients with advanced renal disease; close monitoring of renal function advised if used.⁴²⁰

Common Adverse Effects

With oral therapy, nausea, dyspepsia, headache, dizziness.³⁴¹ ⁴²⁰

With rectal administration, rectal irritation, tenesmus; adverse effects associated with oral administration possible.⁴²⁰

With IV therapy, bleeding,³⁰¹ ³⁰² ³⁰³ ³⁰⁵ ³⁰⁶ ³¹⁰ ³¹⁵ ³¹⁶ ³²² ³²³ ³⁴⁶ ³⁴⁷ ³⁴⁸ ³⁴⁹ ³⁵⁰ ³⁵¹ ³⁵² ³⁵³ ³⁵⁴ transient oliguria,³⁰¹ ³⁰² ³⁰³ ³⁰⁶ ³⁰⁹ ³¹⁴ ³¹⁵ ³²⁴ ³²⁵ ³²⁶ ³²⁹ ³⁴⁶ ³⁴⁷ ³⁴⁸ ³⁵⁰ ³⁵³ ³⁵⁴ ³⁵⁵ ³⁵⁷ ³⁵⁸ ³⁵⁹ ³⁷¹ increases in serum creatinine concentrations,³⁰¹ ³⁰² ³⁰³ ³⁰⁶ ³¹⁴ ³²⁴ ³²⁵ ³²⁶ ³²⁹ ³⁴⁸ ³⁷¹ hyponatremia,³⁰¹ elevated serum potassium concentrations.³⁰¹

Interactions for Indocin

Protein-bound Drugs

Possible pharmacokinetic interaction; observe for adverse effects if used with other protein-bound drugs.^a

Drugs Excreted by the Kidney

Possible pharmacokinetic interaction with drugs that rely on adequate renal function for excretion.³⁰¹ In neonates receiving IV indomethacin, consider dosage adjustment for drugs that rely on adequate renal function for excretion.³⁰¹

Specific Drugs

Drug	Interaction	Comments
ACE inhibitors	Reduced BP response to ACE inhibitor³⁴¹ ⁴²⁰ ⁴⁴⁰ ⁴⁴¹ ⁴⁴² ⁴⁴³ ⁴⁴⁴ ⁴⁴⁵ ⁴⁴⁶ ⁴⁴⁷ Possible deterioration of renal function in individuals with renal impairment⁴²⁰	Monitor BP³⁴¹ ⁴²⁰
Aminoglycosides (amikacin, gentamicin)	Increased plasma aminoglycoside concentrations reported in neonates receiving IV indomethacin³⁰¹ ³⁷²	Monitor serum aminoglycoside concentrations and renal function³⁷²
Angiotensin II receptor antagonists	Reduced BP response to angiotensin II receptor antagonist⁴²⁰ Possible deterioration of renal function in individuals with renal impairment⁴²⁰	Monitor BP⁴²⁰
Antacids (aluminum- or magnesium-containing)	Slight reduction or delay in peak plasma indomethacin concentration^a	Clinical importance not established^a
Anticoagulants	Possible bleeding complications; pharmacodynamic interaction not observed in clinical studies ⁴²⁰	Monitor anticoagulant activity;³⁴¹ ⁴²⁰ caution advised⁴²⁰
Alcohol	Bleeding time prolonged^a
β-adrenergic blocking agents	Reduced BP response to β-adrenergic blocking agent³⁴¹ ⁴²⁰	Monitor BP ⁴²⁰
Cyclosporine	Possible increase in cyclosporine toxicity³⁴¹ ⁴²⁰	Use with caution; monitor renal function³⁴¹ ⁴²⁰
Digoxin	Increased serum concentration and half-life of digoxin³⁰¹ ³⁴¹ ³⁶⁹ ³⁷⁰ ⁴²⁰	Monitor serum digoxin concentrations³⁰¹ ³⁴¹ ⁴²⁰ Consider digoxin dosage reduction in neonates; ³⁶⁹ ³⁷⁰ monitor ECG³⁰¹ ³⁶⁹ ³⁷⁰
Diuretics (furosemide, thiazides)	Reduced natriuretic effects³⁰¹ ³⁴¹ ⁴²⁰ Pharmacokinetic interaction with hydrochlorothiazide unlikely³⁶⁷ ³⁶⁸	Monitor for diuretic efficacy and renal failure⁴²⁰ Concomitant administration of furosemide used to therapeutic advantage in neonates³⁰¹ ³²⁴
Diuretics (potassium-sparing)	Increased serum potassium concentrations³⁴¹ ⁴²⁰ Acute renal failure reported in adults receiving triamterene³⁴¹ ³⁶⁶ ⁴²⁰	Should not be administered concomitantly with triamterene³⁴¹ ⁴²⁰
Hydantoins	Potential pharmacokinetic (protein binding) interaction^a	Monitor for toxicity^a
Hydralazine	Reduced BP response to hydralazine³⁹³	Monitor BP³⁹³
Lithium	Increased plasma lithium concentrations³⁴¹ ⁴²⁰	Monitor for lithium toxicity³⁴¹ ⁴²⁰
Methotrexate	Possible increased plasma methotrexate concentrations⁴²⁰	Caution advised³⁴¹ ⁴²⁰
NSAIAs	NSAIAs including aspirin: Potential for increased risk of GI toxicity with little or no increase in efficacy³⁴¹ ⁴²⁰ Aspirin: No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs⁴²⁰ Aspirin: Decreased plasma indomethacin concentrations reported with concomitant aspirin (3.6 g daily) therapy³⁴¹ ⁴²⁰ Diflunisal: Increased plasma indomethacin concentrations and serious GI adverse effects reported³⁴¹ ⁴²⁰	Concomitant use not recommended³⁴¹ ⁴²⁰
Potassium supplements	Increased serum potassium concentrations³⁶²	Caution advised³⁶²
Prednisolone	Increased plasma concentrations of free prednisolone; total plasma prednisolone concentrations unchanged^a
Probenecid	Increased plasma concentrations of indomethacin³⁴¹ ⁴²⁰	Select and adjust indomethacin dosage with care; lower dosage may be adequate³⁴¹ ⁴²⁰
Sulfonamides	Potential pharmacokinetic (protein binding) interaction^a	Monitor for toxicity^a
Sulfonylureas	Potential pharmacokinetic (protein binding) interaction^a	Monitor for toxicity^a
Thrombolytic agents	Possible bleeding complications^a	Caution advised^a

Indocin Pharmacokinetics

Absorption

Bioavailability

Well absorbed from the GI tract.³⁴¹ ⁴²⁰ Almost completely absorbed following oral administration as conventional or extended-release capsules;³⁴¹ ⁴²⁰ bioavailability following rectal administration is 80–90% of that of the conventional capsule.⁴²⁰

Indomethacin extended-release capsules release 25 mg of drug initially and the remaining 50 mg over 12 hours.³⁴¹

When administered with food, the commercially available conventional capsules and oral suspension are bioequivalent.⁴²⁰

Distribution

Extent

Crosses the placenta and blood-brain barrier.³⁰¹

Concentrations in synovial fluid 20% of those in serum.^a

Distributed into milk.³⁴¹ ⁴²⁰

Plasma Protein Binding

99% (in adults).³⁴¹ ⁴²⁰

Elimination

Metabolism

Metabolized in the liver.³⁴¹ ⁴²⁰

Elimination Route

Undergoes appreciable enterohepatic circulation.³⁰¹ ³⁴¹ ⁴²⁰ Following oral administration, excreted in the urine (60%) and feces (33%) as unchanged drug and metabolites.³⁴¹ ⁴²⁰

Half-life

Adults: 4.5 hours.³⁴¹ ⁴²⁰

Neonates <7 days of age: 20 hours.³⁰¹

Neonates >7 days of age: 12 hours.³⁰¹

Neonates weighing <1 kg: 21 hours.³⁰¹

Neonates weighing >1 kg: 15 hours.³⁰¹

Stability

Storage

Oral

Conventional or Extended-release Capsules

15–30°C.^a ³⁴¹

Suspension

<30°C; avoid temperatures >50°C.⁴²⁰ Protect from freezing.⁴²⁰

Rectal

Suppositories

<30°C; avoid temperatures >40°C (even transiently).⁴²⁰

Parenteral

Powder for Injection

<30°C; protect from light.³⁰¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Reconstitute with preservative-free sterile water for injection or preservative-free 0.9% sodium chloride injection.³⁰¹ Further dilution with IV solutions is not recommended.³⁰¹

Drug Compatibility

Syringe CompatibilityHID
Incompatible
Pantoprazole sodium

Y-Site CompatibilityHID
Compatible
Furosemide
Potassium chloride
Sodium bicarbonate
Sodium nitroprusside
Incompatible
Amino acid injection (TrophAmine)
Calcium gluconate
Cimetidine HCl
Dobutamine HCl
Dopamine HCl
Gentamicin sulfate
Levofloxacin
Tobramycin sulfate
Variable
Dextrose injection

Actions

Inhibits cyclooxygenase-1 (COX-1) and COX-2.³⁰¹ ³⁴¹ ⁴²⁰ ⁴⁵⁵ ⁴⁵⁶ ⁴⁵⁷ ⁴⁵⁸ ⁴⁶¹ ⁴⁶² ⁴⁶³
Pharmacologic actions similar to those of other prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.³⁰¹ ³⁴¹ ⁴²⁰
Permits closure of the ductus arteriosus in premature neonates by inhibiting prostaglandin synthesis.³⁰¹

Advice to Patients

Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.⁴²⁰
Risk of serious cardiovascular events with long-term use.⁴²⁰
Risk of GI bleeding and ulceration.³⁴¹ ⁴²⁰
Risk of serious skin reactions.⁴²⁰ Risk of anaphylactoid and other sensitivity reactions.⁴²⁰
Risk of hepatotoxicity.³⁴¹ ⁴²⁰
Risk of ocular toxicity.³⁴¹ ⁴²⁰
Potential for drug to impair mental alertness; use caution when driving or operating machinery until effects on individual are known.³⁴¹ ⁴²⁰
Importance of notifying clinician if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.⁴²⁰
Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops.³⁴¹ ⁴²⁰
Importance of discontinuing indomethacin and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.⁴²⁰ Importance of seeking immediate medical attention if an anaphylactic reaction occurs.³⁴¹ ⁴²⁰
Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.³⁴¹ ⁴²⁰
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.³⁴¹ ⁴²⁰ Importance of avoiding indomethacin in late pregnancy (third trimester).³⁴¹ ⁴²⁰
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.³⁴¹ ⁴²⁰
Importance of informing patients of other important precautionary information.³⁴¹ ⁴²⁰ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Indomethacin
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	25 mg*	Indocin	Merck
			Indomethacin Capsules	Clonmel, Mutual, Mylan, Par, Pliva, Sandoz, Teva
		50 mg*	Indocin	Merck
			Indomethacin Capsules	Clonmel, Mutual, Mylan, Par, Pliva, Sandoz, Teva
	Capsules, extended-release	75 mg*	Indomethacin Extended-release Capsules	Inwood
	Suspension	25 mg/5 mL	Indocin (with alcohol 1% and sorbic acid)	Merck
Rectal	Suppositories	50 mg*	Indomethacin Suppositories	G&W, PD-RX

Indomethacin Sodium
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IV use only	1 mg (of anhydrous indomethacin)	Indocin I.V.	Ovation

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Indomethacin 25MG Capsules (TEVA PHARMACEUTICALS USA): 30/$15.99 or 60/$20.99

Indomethacin 50MG Capsules (TEVA PHARMACEUTICALS USA): 30/$15.99 or 60/$21.98

Indomethacin CR 75MG Controlled-release Capsules (SANDOZ): 30/$82.15 or 90/$208.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions March 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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344. Lanza FL, Umbenhauer ER, Nelson RS et al. A double-blind randomized placebo controlled gastroscopic study to compare the effects of indomethacin capsules and indomethacin suppositories on the gastric mucosa of human volunteers. J Rheumatol. 1982; 9:415-9. [PubMed 6750118]

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348. Petersen S, Christensen NC et al. Serum indomethacin concentrations after intravenous administration to preterm infants with patent ductus arteriosus. Acta Paediatr Scand. 1981; 70:729-33. [PubMed 7324922]

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352. Campbell AN, Beasley JR, Kenna AP. Indomethacin and gastric perforation in a neonate. Lancet. 1981; 1:1110-1. [IDIS 131255] [PubMed 6112478]

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364. Yeh TF, Raval D, Lilien LD et al. Decreased plasma glucose after indomethacin therapy in premature infants with patent ductus arteriosus. Lancet. 1982; 2:104-5. [IDIS 153454] [PubMed 6123794]

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370. Zarfin Y, Koren G, Perlman M. Digoxin and indomethacin in preterm infants with PDA. J Pediatr. 1984; 105:678-9. [IDIS 190944] [PubMed 6481555]

371. John EG, Vasan U, Hastreiter AR et al. Intravenous indomethacin and changes of renal function in premature infants with patent ductus arteriosus. Pediatr Pharmacol. 1984; 4:11-9.

372. Zarfin Y, Koren G, Maresky D et al. Possible indomethacin-aminoglycoside interaction in preterm infants. J Pediatr. 1985; 106:511-3. [IDIS 197134] [PubMed 3973790]

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376. Weinberger M. Analgesic sensitivity in children with asthma. Pediatrics. 1978; 62(Suppl):910-5. [IDIS 118712] [PubMed 103067]

377. Settipane GA. Aspirin and allergic diseases: a review. Am J Med. 1983; 74(Suppl):102-9. [IDIS 171763] [PubMed 6344621]

378. VanArsdel PP Jr. Aspirin idiosyncracy and tolerance. J Allergy Clin Immunol. 1984; 73:431-3. [IDIS 183975] [PubMed 6423718]

379. Stevenson DD. Diagnosis, prevention, and treatment of adverse reactions to aspirin and nonsteroidal anti-inflammatory drugs. J Allergy Clin Immunol. 1984; 74(4 Part 2):617-22. [IDIS 193318] [PubMed 6436354]

380. Stevenson DD, Mathison DA. Aspirin sensitivity in asthmatics: when may this drug be safe? Postgrad Med. 1985; 78:111-3,116-9. (IDIS 205854)

381. The Upjohn Company. Motrin prescribing information. Kalamazoo, MI; 1985 Jul.

382. McNeil Pharmaceutical. Tolectin DS and Tolectin prescribing information. Spring House, PA; 1985 Aug.

383. Syntex Puerto Rico, Inc. Naprosyn prescribing information. Humacao, PR; 1985 Jun.

384. Pleskow WW, Stevenson DD, Mathison DA et al. Aspirin desensitization in aspirin-sensitive asthmatic patients: clinical manifestations and characterization of the refractory period. J Allergy Clin Immunol. 1982; 69(1 Part 1):11-9. [IDIS 144037] [PubMed 7054250]

385. Thyss A, Milano G, Kubar J et al. Clinical and pharmacokinetic evidence of a life-threatening interaction between methotrexate and ketoprofen. Lancet. 1986; 1:256-8. [IDIS 210465] [PubMed 2868265]

386. Ellison NM, Servi RJ. Acute renal failure and death following sequential intermediate-dose methotrexate and 5-FU: a possible adverse effect due to concomitant indomethacin administration. Cancer Treat Rep. 1985; 69:342-3. [IDIS 198404] [PubMed 3978662]

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391. Hansten PD, Horn JR. Methotrexate and nonsteroidal anti-inflammatory drugs. Drug Interact Newsl. 1986; 6:41-3.

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393. Cinquegrani MP, Liang CS. Indomethacin attenuates the hypotensive action of hydralazine. Clin Pharmacol Ther. 1986; 39:564-70. [IDIS 216068] [PubMed 3698464]

394. Ment LR. Indomethacin for prevention of intraventricular hemorrhage. J Pediatr. 1986; 109:397-8.

395. Barrington KJ. Indomethacin for prevention of intraventricular hemorrhage. J Pediatr. 1986; 109:396-7. [PubMed 3525793]

396. Cowan F. Indomethacin, patent ductus arteriosus, and cerebral blood flow. J Pediatr. 1986; 109:341-4. [IDIS 219997] [PubMed 3734971]

397. Gordon RD, Tunny TJ, Klemm SA et al. Indomethacin and atrial natriuretic peptide in Bartter’s syndrome. N Engl J Med. 1986; 315:459. [IDIS 219396] [PubMed 2942775]

398. Vanhaesebrouck P, Thiery M, Leroy JG et al. Oligohydramnios, renal insufficiency, and ileal perforation in preterm infants after intrauterine exposure to indomethacin. J Pediatr. 1988; 113:738-43. [IDIS 247688] [PubMed 3050004]

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403. Ment LR, Duncan CC, Ehrenkranz RA et al. Randomized low-dose indomethacin trial for prevention of intraventricular hemorrhage in very low birth weight neonates. J Pediatr. 1988; 112:948-55. [IDIS 243715] [PubMed 3373405]

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405. Hanigan WC, Kennedy G, Roemisch F et al. Administration of indomethacin for the prevention of periventricular-intraventricular hemorrhage in high-risk neonates. J Pediatr. 1988; 112:941-7. [IDIS 243714] [PubMed 3373404]

406. Palmer JF. Letter sent to Berger ET, of Merck Sharp & Dohme regarding labeling revisions about gastrointestinal adverse reactions to Indocin (indomethacin). Rockville, MD: Food and Drug Administration, Division of Oncology and Radiopharmaceutical Drug Products; 1988 Sep.

407. Food and Drug Administration. Labeling revisions for NSAIDs. FDA Drug Bull. 1989; 19:3-4.

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412. Jorgensen HS, Christensen HR, Kampmann JP. Interaction between digoxin and indomethacin or ibuprofen. Br J Clin Pharmacol. 1991; 31:108-10. [IDIS 277049] [PubMed 2015162]

413. Sandler DP, Burr FR, Weinberg CR. Nonsteroidal anti-inflammatory drugs and the risk for chronic renal disease. Ann Intern Med. 1991; 115:165-72. [IDIS 283815] [PubMed 2058870]

414. Wagner EH. Nonsteroidal anti-inflammatory drugs and renal disease—still unsettled. Ann Intern Med. 1991; 115:227-8. [IDIS 283820] [PubMed 2058878]

415. Stillman MT, Schlesinger PA. Nonsteroidal anti-inflammatory drug nephrotoxicity: should we be concerned? Arch Intern Med. 1990; 150:268-70.

416. Murray MD, Brater DC. Adverse effects of nonsteroidal anti-inflammatory drugs on renal function. Ann Intern Med. 1990; 112:559-60. [IDIS 265587] [PubMed 2327675]

417. Finch MB, Johnston GD, McDevitt DG. Pharmacokinetics of digoxin alone and in the presence of indomethacin therapy. Br J Clin Pharmacol. 1984; 17:353-5. [IDIS 184093] [PubMed 6712868]

418. Murray MD, Brater DC, Tierney WM et al. Ibuprofen-associated renal impairment in a large general medicine practice. Am J Med Sci. 1990; 299:222-9. [IDIS 301521] [PubMed 2321664]

419. Reviewers’ comments (personal observations).

420. Merck. Indocin (indomethacin) capsules, oral suspension, and suppositories prescribing information. Whitehouse Station, NJ; 2007 Mar.

421. Merck, West Point, PA: Personal communication.

422. Coombs RC, Morgan MEI, Durbin GM et al. Gut blood flow velocities in the newborn: effects of patent ductus arteriosus and parenteral indomethacin. Arch Dis Child. 1990; 65:1067-71. [IDIS 273669] [PubMed 2241229]

423. Rajadurai VS, Yu VYH. Intravenous indomethacin therapy in preterm neonates with patent ductus arteriosus. J Paediatr Child Health. 1991; 27:370-5. [PubMed 1756081]

424. Edwards AD, Wyatt JS, Richardson C et al. Effects of indomethacin on cerebral haemodynamics in very preterm infants. Lancet. 1990; 335:1491-5. [IDIS 267540] [PubMed 1972434]

425. Colditz P, Murphy D, Rolfe P et al. Effect of infusion rate of indomethacin on cerebrovascular responses in preterm infants. Arch Dis Child. 1989; 64:8-12. [IDIS 249853] [PubMed 2923488]

426. Pryds O, Greisen G, Johansen KH. Indomethacin and cerebral blood flow in premature infants treated for patent ductus arteriosus. Eur J Pediatr. 1988; 147:315-6. [PubMed 3391227]

427. Evans DH, Levene MI, Archer LNJ. The effect of indomethacin on cerebral blood-flow velocity in premature infants. Dev Med Child Neurol. 1987; 29:776-82. [PubMed 3691977]

428. Mardoum R, Bejar R, Merritt TA et al. Controlled study of the effects of indomethacin on cerebral blood flow velocities in newborn infants. J Pediatr. 1991; 118:112-5. [IDIS 276665] [PubMed 1986076]

429. Hammerman C, Glaser J, Schimmel MS et al. Continuous versus multiple rapid infusions of indomethacin: effects on cerebral blood flow velocity. Pediatrics. 1995; 95:244-8. [IDIS 342453] [PubMed 7838642]

430. Austin NC, Pairaudeau PW, Hames TK et al. Regional cerebral blood flow velocity changes after indomethacin infusion in preterm infants. Arch Dis Child. 1992; 67:851-4. [IDIS 300009] [PubMed 1519988]

431. Simko A, Mardoum R, Merritt TA et al. Effects on cerebral blood flow velocities of slow and rapid infusion of indomethacin. J Perinatol. 1994; 14:29-35. [PubMed 8169675]

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438. Geigy, Ardsley, NY: Personal communication on diclofenac 28:08.04.

439. Reviewers’ comments (personal observation) on diclofenac 28:08.04.

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