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Indomethacin (Monograph)

Brand names: Indocin, Tivorbex
Drug class: Other Nonsteroidal Anti-inflammatory Agents
CAS number: 53-86-1

Medically reviewed by Drugs.com on Nov 20, 2023. Written by ASHP.

Warning

    Cardiovascular Risk

  • Increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).420 500 502 508 Risk may occur early in treatment and may increase with duration of use.500 502 505 506 508 (See Cardiovascular Thrombotic Effects under Cautions.)

  • Contraindicated in the setting of CABG surgery.508

    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 Indomethacin

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† [off-label] in children ≥2 years of age.420

Pain

Indomethacin (Tivorbex): Relief of mild to moderate acute pain.517

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† [off-label];a however, in the treatment of post-MI pericarditis, NSAIAs are potentially harmful and aspirin is the treatment of choice.491 (See Cardiovascular Thrombotic Effects under Cautions.)

Indomethacin Dosage and Administration

General

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† [off-label]
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† [off-label]
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

Pain
Acute Pain
Oral

Indomethacin (Tivorbex) capsules: 20 mg 3 times daily or 40 mg 2 or 3 times daily.517 This formulation is not interchangeable with other oral formulations.517 (See Bioavailability under Pharmacokinetics.)

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

Detailed Indomethacin dosage information

Cautions for Indomethacin

Contraindications

Warnings/Precautions

Warnings

Cardiovascular Thrombotic Effects

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) increase the risk of serious adverse cardiovascular thrombotic events (e.g., MI, stroke) in patients with or without cardiovascular disease or risk factors for cardiovascular disease.500 502 508

Findings of FDA review of observational studies, meta-analysis of randomized controlled trials, and other published information500 501 502 indicate that NSAIAs may increase the risk of such events by 10–50% or more, depending on the drugs and dosages studied.500

Relative increase in risk appears to be similar in patients with or without known underlying cardiovascular disease or risk factors for cardiovascular disease, but the absolute incidence of serious NSAIA-associated cardiovascular thrombotic events is higher in those with cardiovascular disease or risk factors for cardiovascular disease because of their elevated baseline risk.500 502 506 508

Increased risk may occur early (within the first weeks) following initiation of therapy and may increase with higher dosages and longer durations of use.500 502 505 506 508

In controlled studies, increased risk of MI and stroke observed in patients receiving a selective COX-2 inhibitor for analgesia in first 10–14 days following CABG surgery.508

In patients receiving NSAIAs following MI, increased risk of reinfarction and death observed beginning in the first week of treatment.505 508

Increased 1-year mortality rate observed in patients receiving NSAIAs following MI;500 508 511 absolute mortality rate declined somewhat after the first post-MI year, but the increased relative risk of death persisted over at least the next 4 years.508 511

Some systematic reviews of controlled observational studies and meta-analyses of randomized studies suggest naproxen may be associated with lower risk of cardiovascular thrombotic events compared with other NSAIAs.487 488 489 490 500 501 502 503 506 FDA states that limitations of these studies and indirect comparisons preclude definitive conclusions regarding relative risks of NSAIAs.500

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events throughout therapy, even in those without prior cardiovascular symptoms) and at the lowest effective dosage for the shortest duration necessary.420 500 508

Some clinicians suggest that it may be prudent to avoid NSAIA use, whenever possible, in patients with cardiovascular disease.505 511 512 516 Avoid use in patients with recent MI unless benefits of therapy are expected to outweigh risk of recurrent cardiovascular thrombotic events; if used, monitor for cardiac ischemia.508 Contraindicated in the setting of CABG surgery.508

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.420 502 508 (See Specific Drugs under Interactions.)

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

Hypertension

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 ACE inhibitors, angiotensin II receptor antagonists, β-blockers, and certain diuretics may occur.420 508 (See Specific Drugs under Interactions.)

Heart Failure and Edema

Fluid retention and edema reported.341 420 508

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) may increase morbidity and mortality in patients with heart failure.500 501 504 507 508

NSAIAs may diminish cardiovascular effects of diuretics, ACE inhibitors, or angiotensin II receptor antagonists used to treat heart failure or edema.508 (See Specific Drugs under Interactions.)

Manufacturer recommends avoiding use in patients with severe heart failure unless benefits of therapy are expected to outweigh risk of worsening heart failure; if used, monitor for worsening heart failure.508

Some experts recommend avoiding use, whenever possible, in patients with reduced left ventricular ejection fraction and current or prior symptoms of heart failure.507

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 angiotensin 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

Potentially fatal or life-threatening syndrome of multi-organ hypersensitivity (i.e., drug reaction with eosinophilia and systemic symptoms [DRESS]) reported in patients receiving NSAIAs.1201 Clinical presentation is variable, but typically includes eosinophilia, fever, rash, lymphadenopathy, and/or facial swelling, possibly associated with other organ system involvement (e.g., hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis).1201 Symptoms may resemble those of acute viral infection.1201 Early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present in the absence of rash.1201 If signs or symptoms of DRESS develop, discontinue indomethacin and immediately evaluate the patient.1201

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

Use of NSAIAs during pregnancy at about ≥30 weeks’ gestation can cause premature closure of the fetal ductus arteriosus; use at about ≥20 weeks’ gestation associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment.1200 1201

Effects of NSAIAs on the human fetus during third trimester of pregnancy include prenatal constriction of the ductus arteriosus, tricuspid incompetence, and pulmonary hypertension; nonclosure of the ductus arteriosus during the postnatal period (which may be resistant to medical management); and myocardial degenerative changes, platelet dysfunction with resultant bleeding, intracranial bleeding, renal dysfunction or renal failure, renal injury or dysgenesis potentially resulting in prolonged or permanent renal failure, oligohydramnios, GI bleeding or perforation, and increased risk of necrotizing enterocolitis.1202

Avoid use of NSAIAs in pregnant women at about ≥30 weeks’ gestation; if use required between about 20 and 30 weeks’ gestation, use lowest effective dosage and shortest possible duration of treatment, and consider monitoring amniotic fluid volume via ultrasound examination if treatment duration >48 hours; if oligohydramnios occurs, discontinue drug and follow up according to clinical practice.1200 1201 (See Advice to Patients.)

Fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment observed, on average, following days to weeks of maternal NSAIA use; infrequently, oligohydramnios observed as early as 48 hours after initiation of NSAIAs.1200 1201 Oligohydramnios is often, but not always, reversible (generally within 3–6 days) following NSAIA discontinuance.1200 1201 Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation.1200 1201 In limited number of cases, neonatal renal dysfunction (sometimes irreversible) occurred without oligohydramnios.1200 1201 Some neonatas have required invasive procedures (e.g., exchange transfusion, dialysis).1200 1201 Deaths associated with neonatal renal failure also reported.1200 Limitations of available data (lack of control group; limited information regarding dosage, duration, and timing of drug exposure; concomitant use of other drugs) preclude a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAIA use.1201 Available data on neonatal outcomes generally involved preterm infants; extent to which risks can be generalized to full-term infants is uncertain.1201

Animal data indicate important roles for prostaglandins in kidney development and endometrial vascular permeability, blastocyst implantation, and decidualization.1201 In animal studies, inhibitors of prostaglandin synthesis increased pre- and post-implantation losses; also impaired kidney development at clinically relevant doses.1201

Adverse effects reported in animal reproduction studies with indomethacin (e.g., increased fetal resorptions, retarded fetal ossification, fetal malformations, increased incidence of neuronal necrosis).1201

Effects of indomethacin on labor and delivery not known.1201 In animal studies, NSAIAs increased incidence of dystocia, delayed parturition, and decreased pup survival.1201

Lactation

Distributed into milk; use not recommended.341 420

Fertility

NSAIAs may be associated with reversible infertility in some women.1201 Reversible delays in ovulation observed in limited studies in women receiving NSAIAs; animal studies indicate that inhibitors of prostaglandin synthesis can disrupt prostaglandin-mediated follicular rupture required for ovulation.1201

Consider withdrawal of NSAIAs in women experiencing difficulty conceiving or undergoing evaluation of infertility.1201

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

Safety and efficacy of indomethacin (Tivorbex) for relief of mild to moderate acute pain not established in pediatric patients <18 years of age.517

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

Drug Interactions

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 concentrationa

Clinical importance not establisheda

Anticoagulants

Possible bleeding complications; pharmacodynamic interaction not observed in clinical studies 420

Monitor anticoagulant activity;341 420 caution advised420

Alcohol

Bleeding time prolongeda

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) interactiona

Monitor for toxicitya

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 502 508

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

Pemetrexed

Possible increased risk of pemetrexed-associated myelosuppression, renal toxicity, and GI toxicity1201

Short half-life NSAIAs (e. g., diclofenac, indomethacin): Avoid administration beginning 2 days before and continuing through 2 days after pemetrexed administration1201

Longer half-life NSAIAs (e.g., meloxicam, nabumetone): In the absence of data, avoid administration beginning at least 5 days before and continuing through 2 days after pemetrexed administration1201

Patients with Clcr 45–79 mL/minute: Monitor for myelosuppression, renal toxicity, and GI toxicity1201

Potassium supplements

Increased serum potassium concentrations362

Caution advised362

Prednisolone

Increased plasma concentrations of free prednisolone; total plasma prednisolone concentrations unchangeda

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) interactiona

Monitor for toxicitya

Sulfonylureas

Potential pharmacokinetic (protein binding) interactiona

Monitor for toxicitya

Thrombolytic agents

Possible bleeding complicationsa

Caution adviseda
Indomethacin drug interactions (more detail)

Indomethacin 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

Tivorbex 40-mg capsule under fasted conditions: AUC is 21% lower than that achieved with a 50-mg conventional capsule, but peak plasma concentrations are equivalent.517

Food

Food may slightly decrease or delay peak plasma concentration; however, clinical importance not established.a

Effect of food on pharmacokinetics appears to be comparable for Tivorbex capsules and other conventional indomethacin capsules.517

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

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 Compatibility518

Incompatible

Pantoprazole sodium
Y-Site Compatibility518

Compatible

Furosemide

Insulin regular

Potassium chloride

Sodium bicarbonate

Sodium nitroprusside

Incompatible

Amino acid injection (TrophAmine)

Calcium gluconate

Dobutamine HCl

Dopamine HCl

Gentamicin sulfate

Levofloxacin

Tobramycin sulfate

Actions

Advice to Patients

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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

Indomethacin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

20 mg

Tivorbex

Basiem

25 mg*

Indomethacin Capsules

50 mg*

Indomethacin Capsules

Capsules, extended-release

75 mg*

Indomethacin Extended-release Capsules

Suspension

25 mg/5 mL*

Indocin

Zyla

Indomethacin Oral Suspension

Rectal

Suppositories

50 mg*

Indocin

Zyla

Indomethacin Suppositories

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

Indomethacin Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use only

1 mg (of anhydrous indomethacin)*

Indomethacin Sodium for Injection

AHFS DI Essentials™. © Copyright 2024, Selected Revisions November 29, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

References

236. Mathe AA. False normal dexamethasone suppression test and indomethacin. Lancet. 1982; 2:714. http://www.ncbi.nlm.nih.gov/pubmed/6126646?dopt=AbstractPlus

300. Paulus HE. FDA Arthritis Advisory Committee meeting: postmarketing surveillance of nonsteroidal antiinflammatory drugs. Arthritis Rheum. 1985; 28:1168-9. http://www.ncbi.nlm.nih.gov/pubmed/4052129?dopt=AbstractPlus

301. Ovation Pharmaceuticals. Indocin I.V. (indomethacin sodium trihydrate) prescribing information. Deerfield, IL; 2005 Sep.

302. Yeh TF, Luken JA, Thalji A et al. Intravenous indomethacin therapy in premature infants with persistent ductus arteriosus—a double-blind controlled study. J Pediatr. 1981; 98:137-45. http://www.ncbi.nlm.nih.gov/pubmed/7005415?dopt=AbstractPlus

303. Harris JP, Merritt TA, Alexson CG et al. Parenteral indomethacin for closure of the patent ductus arteriosus: clinical experience with 67 preterm infants. Am J Dis Child. 1982; 136:1005-8. http://www.ncbi.nlm.nih.gov/pubmed/7124692?dopt=AbstractPlus

304. Smith IJ, Goss I, Congdon PJ. Intravenous indomethacin for patent ductus arteriosus. Arch Dis Child. 1984; 59:537-41. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1628746&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/6742874?dopt=AbstractPlus

305. Merritt TA, Harris JP, Roghmann K et al. Early closure of the patent ductus arteriosus in very low-birth-weight infants: a controlled trial. J Pediatr. 1981; 99:281-6. http://www.ncbi.nlm.nih.gov/pubmed/7019406?dopt=AbstractPlus

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