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Indomethacin: Drug information

Indomethacin: Drug information
(For additional information see "Indomethacin: Patient drug information" and see "Indomethacin: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Serious cardiovascular thrombotic events:

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

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

Serious gastrointestinal bleeding, ulceration, and perforation:

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.

Brand Names: US
  • Indocin;
  • Tivorbex [DSC]
Brand Names: Canada
  • AURO-Indomethacin;
  • MINT-Indomethacin;
  • ODAN-Indomethacin;
  • TEVA-Indomethacin
Pharmacologic Category
  • Analgesic, Nonopioid;
  • Nonsteroidal Anti-inflammatory Drug (NSAID), Oral;
  • Nonsteroidal Anti-inflammatory Drug (NSAID), Parenteral
Dosing: Adult

Note: Safety: Use the lowest effective dose for the shortest duration of time. Avoid or use with caution in patients at risk for or with existing cardiovascular disease, GI disease, kidney impairment, chronic liver disease, or a bleeding diathesis due to greater risk for adverse events. Consider administering in combination with a proton pump inhibitor in patients at risk for GI bleeding (eg, taking dual antiplatelet therapy or an anticoagulant, ≥60 years of age, high indomethacin doses) (Ref).

Acute pain

Acute pain (mild to moderate): Note: Indomethacin 20 mg capsules (brand and generic) have been discontinued in the United States for >1 year.

Oral (Tivorbex only): 20 mg 3 times daily or 40 mg 2 or 3 times daily.

Ankylosing spondylosis, osteoarthritis, or rheumatoid arthritis

Ankylosing spondylosis, osteoarthritis, or rheumatoid arthritis: Note: Use lowest effective dose for the shortest duration possible.

Oral (immediate release [excluding Tivorbex]), rectal: 25 mg 2 to 3 times daily; if well tolerated, increase daily dosage by 25 or 50 mg at weekly intervals until satisfactory response or a total daily dose of 150 to 200 mg/day (maximum dose: 200 mg/day) is reached. In patients with arthritis and persistent night pain and/or morning stiffness may give the larger portion (up to maximum of 100 mg) of the total daily dose at bedtime.

Oral (ER capsules): Initial: 75 mg once daily, may increase to 75 mg twice daily (maximum dose: 150 mg/day).

Bursitis/tendinopathy of the shoulder

Bursitis/tendinopathy of the shoulder: Oral (excluding Tivorbex), rectal: Initial dose: 75 to 150 mg/day in 3 to 4 divided doses or 1 to 2 divided doses for extended release; usual treatment is 7 to 14 days; discontinue after signs/symptoms of inflammation have been controlled for several days.

Gout, treatment, acute flares

Gout, treatment, acute flares:

Oral (generic IR capsules, suspension), rectal (suppository): 50 mg 3 times daily within 24 to 48 hours of flare onset; reduce dose as symptoms improve. Discontinue a few days after resolution of clinical signs (usual total duration: 5 to 7 days); longer duration may be required if therapy is delayed (Ref).

Pericarditis, acute or recurrent

Pericarditis, acute or recurrent (off-label use):

Note: In patients with an indication for aspirin (eg, coronary artery disease), aspirin is preferred over other nonsteroidal anti-inflammatory drugs (NSAIDs). Non-aspirin NSAIDs should be avoided in patients with pericarditis secondary to acute myocardial infarction given lack of benefit and potential harm (Ref).

Oral: Initial: 25 to 50 mg every 8 hours until resolution of symptoms for at least 24 hours and normalization of inflammatory biomarkers (eg, C-reactive protein) if monitored; initial therapy typically lasts for ≥1 to 2 weeks. Gradually taper by decreasing each dose by 25 mg every 1 to 2 weeks (eg, if initially 50 mg every 8 hours, taper to 25 mg every 8 hours, then discontinue); some clinicians may taper more slowly before discontinuing therapy (eg, if inititally 25 mg every 8 hours, taper to 25 mg every 12 hours, then 25 mg once daily, then discontinue); during taper, ensure patient remains asymptomatic and inflammatory biomarkers remain normal (if monitored). Use in combination with colchicine. In patients at risk of NSAID-related GI toxicity, prophylaxis (generally with a proton pump inhibitor) is recommended (Ref).

Prevention of pancreatitis post-endoscopic retrograde cholangiopancreatography

Prevention of pancreatitis post-endoscopic retrograde cholangiopancreatography (off-label use): Rectal: 100 mg immediately before or after endoscopic retrograde cholangiopancreatography (Ref).

Tocolysis

Tocolysis (off-label use): Oral, rectal: Initial: 50 to 100 mg orally or rectally, followed by 25 mg every 4 to 6 hours orally in women between 24 and 32 weeks' gestation. Duration of treatment is generally limited to 48 to 72 hours (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function:

CrCl ≥60 mL/minute: No dosage adjustment necessary (Ref).

CrCl >30 to <60 mL/minute: No dosage adjustment necessary (Ref); however, use the lowest effective dose for the shortest duration possible. Use of analgesics other than nonsteroidal anti-inflammatory drugs (NSAIDs) or topical NSAIDs may be preferred. Avoid use in patients at high risk for acute kidney injury (ie, volume depleted, hypotensive, older adults, taking concurrent nephrotoxic medications) (Ref).

CrCl ≤30 mL/minute: Avoid use due to increased risk of acute kidney injury (Ref).

Hemodialysis, intermittent (thrice weekly): Slightly dialyzable (20%) (Ref): Avoid use, as patients with end-stage kidney disease may be at increased risk for bleeding (eg, GI), cardiovascular adverse effects, and loss of residual kidney function (Ref).

Peritoneal dialysis: Unlikely to be significantly dialyzable (high protein binding): Avoid use, as patients with end-stage kidney disease may be at increased risk for bleeding (eg, GI), cardiovascular adverse effects, and loss of residual kidney function (Ref).

CRRT: Avoid use (may worsen kidney injury) (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Avoid use (may worsen kidney injury) (Ref).

Acute kidney injury while on indomethacin therapy: Discontinue use (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution to avoid adverse effects and discontinue if hepatic function worsens.

Dosing: Older Adult

Avoid use (Ref).

Dosing: Pediatric

(For additional information see "Indomethacin: Pediatric drug information")

Inflammatory/rheumatoid disorders

Inflammatory/rheumatoid disorders: Note: Use lowest effective dose for the shortest duration:

Immediate release: Children ≥2 years and Adolescents (limited data available in ages <15 years): Oral (immediate release [excluding Tivorbex]): Initial: 1 to 2 mg/kg/day in 3 to 4 divided doses; usual initial adult dose range: 50 to 75 mg/day; maximum daily dose: 4 mg/kg/day or 200 mg/day, whichever is less (Ref).

Extended release: Adolescents ≥15 years: Oral: Initial: 75 mg once daily, may increase to 75 mg twice daily; maximum daily dose: 150 mg/day (Ref).

Gout, acute flares

Gout, acute flares (alternative agent): Adolescents ≥15 years: Immediate release (capsules [excluding Tivorbex], suspension, suppository): Oral, Rectal: 50 mg 3 times daily; once pain is tolerable, rapidly reduce until completely discontinued; pain relief begins 2 to 4 hours after initiating therapy with tenderness and warmth beginning to subside in 24 to 36 hours and swelling gradually resolving in 3 to 5 days (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Oral, Rectal: There are no specific pediatric dosage adjustments provided in the manufacturer's labeling, not recommended in patients with advanced renal disease; some experts have suggested the following:

KDIGO guidelines provide the following recommendations for NSAIDs (Ref):

eGFR 30 to <60 mL/minute/1.73 m2: Temporarily discontinue in patients with intercurrent disease that increases risk of acute kidney injury.

eGFR <30 mL/minute/1.73 m2: Avoid use.

Dosing: Hepatic Impairment: Pediatric

Oral, Rectal: There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Gastrointestinal: Vomiting (≤12%)

Hematologic & oncologic: Postoperative hemorrhage (≤11%)

Nervous system: Headache (12% to 16%)

1% to 10%:

Cardiovascular: Presyncope (≤3%), syncope (≤2%)

Dermatologic: Hyperhidrosis (2%), pruritus (1% to 4%), skin rash (1% to 2%)

Endocrine & metabolic: Hot flash (2%)

Gastrointestinal: Abdominal distress (1% to 3%), abdominal pain (<3%), constipation (≤6%), decreased appetite (≥2%), diarrhea (<3%), dyspepsia (2% to 9%), epigastric pain (3% to 9%), heartburn (3% to 9%), nausea (3% to 9%)

Otic: Tinnitus (>1%)

Nervous system: Depression (1% to 3%), dizziness (3% to 9%), drowsiness (1% to 3%), fatigue (1% to 3%), malaise (1% to 3%), vertigo (1% to 3%)

Miscellaneous: Swelling (3%; postprocedural)

Frequency not defined: Hepatic: Increased serum alanine aminotransferase, increased serum aspartate aminotransferase

<1%:

Cardiovascular: Cardiac arrhythmia, cardiac failure, chest pain, edema, flushing, hypertension, hypotension, palpitations, shock, tachycardia, vasculitis

Dermatologic: Alopecia, diaphoresis, ecchymoses, erythema multiforme, erythema nodosum, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria

Gastrointestinal: Anorexia, aphthous stomatitis, bloating, flatulence, gastroenteritis, gastrointestinal hemorrhage, gastrointestinal perforation, gastrointestinal ulcer, ileitis (regional), intestinal obstruction, intestinal stenosis, pancreatitis, ulcerative colitis

Genitourinary: Breast hypertrophy, breast tenderness, hematuria, nephrotic syndrome, peptic ulcer, proctitis, proteinuria, vaginal hemorrhage

Endocrine & metabolic: Fluid retention, glycosuria, gynecomastia, hyperglycemia, hyperkalemia, weight gain

Hematologic & oncologic: Agranulocytosis, anemia, aplastic anemia, bone marrow depression, disseminated intravascular coagulation, hemolytic anemia, immune thrombocytopenia, leukopenia, nonthrombocytopenic purpura, petechiae, rectal hemorrhage

Hepatic: Hepatic failure, hepatic necrosis, jaundice, toxic hepatitis

Hypersensitivity: Anaphylaxis, angioedema

Nervous system: Anxiety, coma, confusion, depersonalization, dysarthria, exacerbation of epilepsy, exacerbation of Parkinson disease, insomnia, involuntary muscle movements, myasthenia, nervousness, paresthesia, peripheral neuropathy, psychic disturbance, psychosis, seizure

Ophthalmic: Blurred vision, corneal deposits, diplopia, maculopathy, retinal disturbance

Otic: Auditory disturbance, deafness

Renal: Increased blood urea nitrogen, interstitial nephritis, renal failure syndrome, renal insufficiency

Respiratory: Acute respiratory distress, asthma, dyspnea, epistaxis, pulmonary edema

Miscellaneous: Fever

Frequency not defined:

Cardiovascular: Acute myocardial infarction, cerebrovascular accident, coronary thrombosis

Gastrointestinal: Gastrointestinal inflammation

Postmarketing:

Gastrointestinal: Tenesmus (rectal)

Hepatic: Hepatotoxicity (idiosyncratic) (Chalasani 2014)

Immunologic: Drug reaction with eosinophilia and systemic symptoms

Contraindications

Hypersensitivity (eg, anaphylactic reactions, serious skin reactions) to indomethacin or any component of the formulation; use in the setting of coronary artery bypass graft (CABG) surgery; history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAID agents; patients with a history of proctitis or recent rectal bleeding (suppositories).

Neonates (IV only): Necrotizing enterocolitis (proven or suspected); significant kidney impairment; active bleeding (including intracranial hemorrhage and gastrointestinal bleeding), thrombocytopenia, coagulation defects; untreated infection (proven or suspected); congenital heart disease where patency of the ductus arteriosus is necessary for adequate pulmonary or systemic blood flow (eg, pulmonary atresia, severe tetralogy of Fallot, severe coarctation of the aorta)

Canadian labeling: Additional contraindications (not in US labeling): Severe uncontrolled heart failure; known hyperkalemia; active gastric/duodenal/peptic ulcer; active GI bleed; history of recurrent GI ulceration; active GI inflammatory disease; cerebrovascular bleeding or other bleeding disorders; severe hepatic impairment or active liver disease; severe kidney impairment (CrCl <30 mL/minute) or deteriorating kidney function; concurrent use with other NSAIDs; complete or partial syndrome of nasal polyps; children and adolescents <14 years of age; breast-feeding; pregnancy (third trimester)

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid reactions: Even in patients without prior exposure anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Contraindicated in patients who experience bronchospasm, asthma, rhinitis, or urticaria with nonsteroidal anti-inflammatory drug (NSAID) or aspirin therapy.

• Cardiovascular events: [US Boxed Warning]: NSAIDs cause an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events, including MI and stroke. Risk may occur early during treatment and may increase with duration of use. Relative risk appears to be similar in those with and without known cardiovascular disease or risk factors for cardiovascular disease; however, absolute incidence of serious cardiovascular thrombotic events (which may occur early during treatment) was higher in patients with known cardiovascular disease or risk factors and in those receiving higher doses. New-onset hypertension or exacerbation of hypertension may occur (NSAIDs may also impair response to ACE inhibitors, thiazide diuretics, or loop diuretics); may contribute to cardiovascular events; monitor blood pressure; use with caution in patients with hypertension. May cause sodium and fluid retention, use with caution in patients with edema. Avoid use in heart failure (FDA 2015). Avoid use in patients with recent MI unless benefits outweigh risk of cardiovascular thrombotic events. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.

• CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving). Headache may occur; cessation of therapy required if headache persists after dosage reduction.

• Drug reaction with eosinophilia and systemic symptoms: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, has been reported with NSAIDs. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinue therapy and further evaluate if DRESS is suspected.

• GI events: [US Boxed Warning]: NSAIDs cause increased risk of serious GI inflammation, ulceration, bleeding, and perforation (may be fatal); elderly patients and patients with history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events. These events may occur at any time during therapy and without warning. Avoid use in patients with active GI bleeding. In patients with a history of acute lower GI bleeding, avoid use of non-aspirin NSAIDs, especially if due to angioectasia or diverticulosis (Strate 2016). Use caution with a history of GI ulcers, concurrent therapy known to increase the risk of GI bleeding (eg, aspirin, anticoagulants and/or corticosteroids, selective serotonin reuptake inhibitors), advanced hepatic disease, coagulopathy, smoking, use of alcohol, or in older or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with aspirin, a substantial increase in the risk of GI complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended (Bhatt 2008).

• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).

• Hepatic effects: Transaminase elevations have been reported with use; closely monitor patients with any abnormal liver function test (LFT). Rare, sometimes fatal severe hepatic reactions (eg, fulminant hepatitis, hepatic necrosis, hepatic failure) have occurred with NSAID use; discontinue immediately if clinical signs or symptoms of liver disease develop or if systemic manifestations occur.

• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in older patients, diabetic patients, patients with kidney disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE inhibitors). Monitor potassium closely.

• Kidney effects: NSAID use may compromise existing kidney function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause kidney decompensation (usually reversible). Patients with impaired kidney function, dehydration, hypovolemia, heart failure, hepatic impairment, those taking diuretics, and ACE inhibitors, and older patients are at greater risk of kidney toxicity. Rehydrate patient before starting therapy; monitor kidney function closely. Long-term NSAID use may result in renal papillary necrosis and other kidney injury.

• Ophthalmic effects: Prolonged therapy may cause corneal deposits and retinal disturbances, including those of the macula. Discontinue use with blurred or diminished vision and perform ophthalmologic exam. Periodically evaluate vision in all patients receiving long-term therapy.

• Skin reactions: NSAIDs may cause potentially fatal serious skin adverse events, including drug reaction with eosinophilia and systemic symptoms, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis; may occur without warning; discontinue use at first sign of skin rash (or any other hypersensitivity).

Disease-related concerns:

• Aseptic meningitis: May increase the risk of aseptic meningitis, especially in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders.

• Asthma: Contraindicated in patients with aspirin-sensitive asthma; severe and potentially fatal bronchospasm may occur. Use caution in patients with other forms of asthma.

• Bariatric surgery: Gastric ulceration: Avoid chronic use of oral nonselective NSAIDs after bariatric surgery; development of anastomotic ulcerations/perforations may occur (Bhangu 2014; Mechanick 2020). Short-term use of celecoxib or IV ketorolac are recommended as part of a multimodal pain management strategy for postoperative pain (Chou 2016; Horsley 2019; Thorell 2016).

• Coronary artery bypass graft surgery: [US Boxed Warning]: Use is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Risk of MI and stroke may be increased with use following CABG surgery.

• Depression: Use caution with depression; use may aggravate depression or other psychiatric disorders.

• Epilepsy: Use caution with epilepsy; use may aggravate this condition.

• Hepatic impairment: Use with caution in patients with hepatic impairment; patients with advanced hepatic disease are at an increased risk of GI bleeding and kidney failure with NSAIDs (AASLD [Biggins 2021]; AASLD [Runyon 2013]).

• Kidney impairment: Avoid use in patients with advanced kidney disease; discontinue use with persistent or worsening abnormal kidney function tests. The injection formulation is contraindicated in neonates with significant kidney impairment.

• Parkinsonism: Use caution with Parkinson disease; use may aggravate this condition.

Special populations:

• Older adult: Older adult patients are at greater risk for serious GI, cardiovascular, and/or kidney adverse events; use with caution. Indomethacin may cause confusion or, rarely, psychosis; remain alert to the possibility of such adverse reactions in older adult patients.

• Pediatric: Oral: There have been cases of hepatotoxicity reported in pediatric patients with juvenile rheumatoid arthritis, including fatalities. Closely monitor if needed in pediatric patients ≥2 years and periodically assess liver function.

Other warnings/precautions:

• Appropriate use: Tivorbex is not indicated for long-term use.

• Surgical/dental procedures: Withhold for at least 4 to 6 half-lives prior to surgical or dental procedures.

Warnings: Additional Pediatric Considerations

A single-center, 10-year, retrospective review of pediatric patients diagnosed with acute kidney injury (AKI) (n=1,015; ages: ≤18 years) reported nonsteroidal anti-inflammatory drugs (NSAIDs) as a potential cause of AKI in 2.7% of patients (n=27); a higher incidence (6.6%) was reported when additional exclusion factors were included in the data analysis. Dosing information was available for 74% of the NSAID-associated AKI cases (n=20); dosing was within the recommended range in 75% (n=15) of these cases. The median age of children with NSAID-associated AKI was 14.7 years (range: 0.5 to 17.7 years) and 15% of patients were <5 years and more likely to require dialysis than the older patients. Some experts suggest the incidence of NSAID-associated AKI found in this study is conservative due to aggressive exclusion criteria (eg, concurrent aminoglycoside or other nephrotoxic therapy) and the actual incidence may be higher (Brophy 2013; Misurac 2013).

Product Availability

Indomethacin 20 mg capsules (brand and generic) have been discontinued in the United States for >1 year.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Tivorbex: 20 mg [DSC] [contains fd&c blue #1 (brilliant blue), fd&c blue #2 (indigotine,indigo carmine), fd&c red #40 (allura red ac dye)]

Generic: 20 mg [DSC], 25 mg, 50 mg

Capsule Extended Release, Oral:

Generic: 75 mg

Solution Reconstituted, Intravenous:

Generic: 1 mg (1 ea)

Solution Reconstituted, Intravenous [preservative free]:

Generic: 1 mg (1 ea)

Suppository, Rectal:

Indocin: 50 mg (30 ea)

Generic: 50 mg (30 ea)

Suspension, Oral:

Indocin: 25 mg/5 mL (237 mL) [contains alcohol, usp; pineapple-coconut-mint flavor]

Generic: 25 mg/5 mL (237 mL)

Generic Equivalent Available: US

Yes

Pricing: US

Capsule Extended Release (Indomethacin ER Oral)

75 mg (per each): $3.00 - $3.04

Capsules (Indomethacin Oral)

25 mg (per each): $0.38 - $0.55

50 mg (per each): $0.64 - $0.78

Solution (reconstituted) (Indomethacin Sodium Intravenous)

1 mg (per each): $445.49 - $634.73

Suppository (Indocin Rectal)

50 mg (per each): $434.29

Suppository (Indomethacin Rectal)

50 mg (per each): $412.57

Suspension (Indocin Oral)

25 mg/5 mL (per mL): $11.99

Suspension (Indomethacin Oral)

25 mg/5 mL (per mL): $10.78

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Generic: 25 mg, 50 mg

Suppository, Rectal:

Generic: 50 mg (30 ea); 100 mg (30 ea)

Administration: Adult

Oral: Administer with food, immediately after meals, or with milk or antacids to decrease GI adverse effects. ER capsules must be swallowed whole; do not crush.

Bariatric surgery: Capsule, extended release. Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Do not cut, crush, or chew. Nonsteroidal anti-inflammatory drugs are not recommended for routine use after bariatric surgery. Where possible, cyclooxygenase-2 selective therapy should be used.

Rectal: For rectal use only; not for oral or intravaginal use.

Administration: Pediatric

Oral: Administer with food, milk, or antacids to decrease GI adverse effects; extended-release capsules must be swallowed whole; do not crush or chew.

Parenteral: For IV administration only; do not administer via IV bolus or IV infusion via an umbilical catheter into vessels near the superior mesenteric artery, as these may cause vasoconstriction and can compromise blood flow to the intestines. Administer over 20 to 30 minutes.

Rectal: For rectal use only; not for oral or intravaginal use.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Indocin capsules: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/016059s101lbl.pdf#page=24

Indocin oral suspension: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/018332s042lbl.pdf#page=24

Indocin rectal suppository: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/017814s044lbl.pdf#page=24

Indocin SR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/018185s058lbl.pdf#page=25

Tivorbex: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/204768s008lbl.pdf#page=25

Use: Labeled Indications

Acute pain, mild to moderate (Tivorbex only): Treatment of mild to moderate acute pain in adults.

Ankylosing spondylitis (excluding Tivorbex): Treatment of moderate to severe ankylosing spondylitis.

Bursitis/tendinopathy of the shoulder (excluding Tivorbex): Treatment of acute painful bursitis and/or tendinopathy of the shoulder.

Gout, treatment, acute flares (generic IR capsules, oral suspension, rectal suppositories): Treatment of acute gout flares.

Osteoarthritis (excluding Tivorbex): Treatment of moderate to severe osteoarthritis.

Patent ductus arteriosus (IV only): To close a hemodynamically significant patent ductus arteriosus in premature infants weighing between 500 and 1,750 g when 48 hours usual medical management (eg, fluid restriction, diuretics, digitalis, respiratory support) is ineffective.

Rheumatoid arthritis (excluding Tivorbex): Treatment of moderate to severe rheumatoid arthritis, including acute flares of chronic disease.

Use: Off-Label: Adult

Pericarditis, acute or recurrent; Prevention of pancreatitis post-endoscopic retrograde cholangiopancreatography; Tocolysis

Medication Safety Issues
Sound-alike/look-alike issues:

Indocin may be confused with Imodium, Lincocin, Minocin, Vicodin

Older Adult: High-Risk Medication:

Beers Criteria: Indomethacin is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to an increased risk of GI bleeding, peptic ulcer disease and acute kidney injury in older adults. Indomethacin is more likely to have NSAID-related adverse events and adverse CNS effects in older adults compared to other NSAIDs (Beers Criteria [AGS 2023]).

Metabolism/Transport Effects

Substrate of CYP2C19 (minor), CYP2C9 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-Aminosalicylic Acid Derivatives. Risk C: Monitor therapy

Abrocitinib: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the antiplatelet effect of Abrocitinib. Risk X: Avoid combination

Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Acemetacin: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of GI bleeding may be increased with this combination. Risk C: Monitor therapy

Aliskiren: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Risk C: Monitor therapy

Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Anagrelide: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Apixaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Apixaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of apixaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Bemiparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin and nonsteroidal anti-inflammatory agents (NSAIDs) due to the increased risk of bleeding. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Risk C: Monitor therapy

Bremelanotide: May decrease the serum concentration of Indomethacin. Risk C: Monitor therapy

Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy

CycloSPORINE (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (eg, hypertension) during concomitant therapy with NSAIDs. Risk D: Consider therapy modification

Dabigatran Etexilate: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of dabigatran and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Deferasirox: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy

Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Diflunisal: May enhance the adverse/toxic effect of Indomethacin. Specifically, the risk for gastrointestinal hemorrhage may be increased. Diflunisal may enhance the antiplatelet effect of Indomethacin. Diflunisal may increase the serum concentration of Indomethacin. Risk X: Avoid combination

Digoxin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin. Risk C: Monitor therapy

Drospirenone-Containing Products: May enhance the hyperkalemic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Edoxaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of edoxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Enoxaparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue nonsteroidal anti-inflammatory agents (NSAIDs) prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Eplerenone: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy

Glucagon and Glucagon Analogs: Indomethacin may diminish the therapeutic effect of Glucagon and Glucagon Analogs. Risk C: Monitor therapy

Haloperidol: Indomethacin may enhance the CNS depressant effect of Haloperidol. Risk C: Monitor therapy

Heparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or nonsteroidal anti-inflammatory agents (NSAIDs) if coadministration is required. Risk D: Consider therapy modification

Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Risk C: Monitor therapy

HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Risk C: Monitor therapy

Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Ketorolac (Nasal): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Ketorolac (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Ketorolac (Systemic). Risk X: Avoid combination

Lecanemab: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. Management: Consider reducing the lithium dose when initiating a NSAID. Monitor for increased lithium therapeutic/toxic effects if a NSAID is initiated/dose increased, or decreased effects if a NSAID is discontinued/dose decreased. Risk D: Consider therapy modification

Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended. Risk D: Consider therapy modification

Macimorelin: Nonsteroidal Anti-Inflammatory Agents may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination

MetFORMIN: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of MetFORMIN. Risk C: Monitor therapy

Methotrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate. Management: Avoid coadministration of higher dose methotrexate (such as that used for the treatment of oncologic conditions) and NSAIDs. Use caution if coadministering lower dose methotrexate and NSAIDs. Risk D: Consider therapy modification

Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy

Mifamurtide: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Mifamurtide. Risk X: Avoid combination

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Naftazone: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of other Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk for gastrointestinal toxicity is increased. Risk X: Avoid combination

Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of gastrointestinal (GI) toxicity is increased. Management: Coadministration of systemic nonsteroidal anti-inflammatory drugs (NSAIDs) and topical NSAIDs is not recommended. If systemic NSAIDs and topical NSAIDs, ensure the benefits outweigh the risks and monitor for increased NSAID toxicities. Risk D: Consider therapy modification

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy

Omacetaxine: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Risk C: Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Phenylbutazone: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Pirtobrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Polyethylene Glycol-Electrolyte Solution: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Potassium Salts: Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium Salts. Risk C: Monitor therapy

Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy

PRALAtrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Avoid coadministration of pralatrexate with nonsteroidal anti-inflammatory drugs (NSAIDs). If coadministration cannot be avoided, closely monitor for increased pralatrexate serum levels or toxicity. Risk D: Consider therapy modification

Probenecid: May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Prostaglandins (Ophthalmic): Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic). Risk C: Monitor therapy

Quinolones: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolones. Risk C: Monitor therapy

Rivaroxaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Salicylates: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Management: Nonselective NSAIDs may reduce aspirin's cardioprotective effects. Administer ibuprofen 30-120 minutes after immediate-release aspirin, 2 to 4 hours after extended-release aspirin, or 8 hours before aspirin. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk. Risk D: Consider therapy modification

Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification

Sodium Phosphates: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy

Tacrolimus (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

Tenofovir Products: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose due to a potential risk of acute renal failure. Diclofenac appears to confer the most risk. Risk D: Consider therapy modification

Tenoxicam: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Thiazide and Thiazide-Like Diuretics: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy

Tiludronate: Indomethacin may increase the serum concentration of Tiludronate. Management: Separate doses of tiludronate at least two hours before or two hours after indomethacin. Risk D: Consider therapy modification

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Tolperisone: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Tolperisone. Specifically, the risk of hypersensitivity reactions may be increased. Tolperisone may enhance the therapeutic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Triamterene: May enhance the adverse/toxic effect of Indomethacin. Specifically, the risk for renal failure and hyperkalemia may be increased. Management: Consider alternatives to concomitant treatment with triamterene and indomethacin. If the combination cannot be avoided, monitor for development of renal failure and hyperkalemia. Risk D: Consider therapy modification

Tricyclic Antidepressants: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of major adverse cardiac events (MACE), hemorrhagic stroke, ischemic stroke, and heart failure may be increased. Tricyclic Antidepressants may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination

Vancomycin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin. Risk C: Monitor therapy

Vasopressin: Indomethacin may enhance the therapeutic effect of Vasopressin. Specifically, vasopressin effects on cardiac index and systemic vascular resistance may be enhanced. Risk C: Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor coagulation status closely and advise patients to promptly report any evidence of bleeding or bruising. Risk D: Consider therapy modification

Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Food Interactions

Food may decrease the rate but not the extent of absorption. Indomethacin peak serum levels may be delayed if taken with food. Management: Administer with food or milk to minimize GI upset.

Reproductive Considerations

Nonsteroidal anti-inflammatory drugs (NSAIDs) may delay or prevent rupture of ovarian follicles. This may be associated with infertility that is reversible upon discontinuation of the medication. Consider discontinuing use in patients having difficulty conceiving or those undergoing investigation of fertility.

Based on available information, NSAIDs can be continued in males with rheumatic and musculoskeletal diseases who are planning to father a child (ACR [Sammaritano 2020]).

Pregnancy Considerations

Indomethacin crosses the placenta.

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) close to conception may be associated with an increased risk of miscarriage due to cyclooxygenase-2 inhibition interfering with implantation (Bermas 2014; Bloor 2013).

Birth defects have been observed following in utero NSAID exposure in some studies; however, data are conflicting (Bloor 2013). Nonteratogenic effects, including prenatal constriction of the ductus arteriosus, persistent pulmonary hypertension of the newborn, oligohydramnios, necrotizing enterocolitis, kidney dysfunction or failure, and intracranial hemorrhage have been observed in the fetus/neonate following in utero NSAID exposure (Bermas 2014; Bloor 2013). Maternal NSAID use may cause fetal kidney dysfunction leading to oligohydramnios. Although rare, this may occur as early as 20 weeks' gestation and is more likely to occur with prolonged maternal use. Oligohydramnios may be reversible following discontinuation of the NSAID (Dathe 2019; FDA 2020). In addition, nonclosure of the ductus arteriosus postnatally may occur and be resistant to medical management (Bermas 2014; Bloor 2013).

Maternal use of NSAIDs should be avoided beginning at 20 weeks' gestation. If NSAID use is necessary between 20 and 30 weeks' gestation, limit use to the lowest effective dose and shortest duration possible; consider ultrasound monitoring of amniotic fluid if treatment extends beyond 48 hours and discontinue the NSAID if oligohydramnios is found (FDA 2020). Because NSAIDs may cause premature closure of the ductus arteriosus, product labeling for indomethacin specifically states use should be avoided starting at 30 weeks' gestation.

The clearance of indomethacin may be increased during pregnancy (Rytting 2014). Additional studies are needed to evaluate the influence of maternal CYP2C9 genotype, formation of the O-desmethylindomethacin (DMI) metabolite, and clearance of indomethacin (Shah 2019).

NSAIDs, such as indomethacin, are an effective short-term (≤48 hours) treatment option for the management of preterm labor to prolong pregnancy and allow for the administration of antenatal steroids. When choosing a specific agent, the benefits of the available tocolytic agents should be weighed against the potential risks for the individual person. Use >48 hours may increase the risk of in utero constriction of the ductus arteriosus and oligohydramnios (ACOG 2016).

Based on available information, NSAIDs can be continued during the first 2 trimesters of pregnancy in patients with rheumatic and musculoskeletal diseases; use in the third trimester is not recommended (ACR [Sammaritano 2020]).

NSAIDs may be used as part of a multimodal approach to pain relief following cesarean delivery (ACOG 2019).

Breastfeeding Considerations

Indomethacin is present in breast milk.

The relative infant dose (RID) of indomethacin is 8.6% when calculated using the highest breast milk concentration located and compared to an IV infant therapeutic dose of 0.2 mg/kg/day.

In general, breastfeeding is considered acceptable when an RID of a medication is <10% (Anderson 2016; Ito 2000).

The RID of indomethacin was calculated using a milk concentration of 115 mcg/L, providing an estimated infant dose via breast milk of 0.017 mg/kg/day. This milk concentration was obtained following maternal administration of indomethacin 1.43 mg/kg/day. Using all data from this study, the average concentration in breast milk is 0.27% of the weight-adjusted maternal dose (dose range: 0.94 to 4.29 mg/kg/day). Indomethacin was also detected in the plasma of a breastfeeding infant (Lebedevs 1991).

Seizures in a breastfeeding infant were observed in one case report (Eeg-Olofsson 1978). Hypertensive crisis and psychiatric side effects have been noted in women following use of indomethacin for postpartum analgesia (Clunie 2003; Makris 2004).

Nonopioid analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs), are preferred for breastfeeding patients who require pain control peripartum or for surgery outside of the postpartum period (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]. Indomethacin may be used for the treatment of maternal pain in postpartum women who wish to breastfeed (ABM [Martin 2018]). NSAIDs are considered compatible for the treatment of rheumatic and musculoskeletal diseases in lactating patients; agents with a short half-life and established safety data in infants may be preferred (ACR [Sammaritano 2020]).

The manufacturer recommends that the decision to breastfeed during therapy consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Maternal use of NSAIDs should be avoided if the breastfeeding infant has platelet dysfunction, thrombocytopenia, or a ductal-dependent cardiac lesion (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]; Bloor 2013).

The therapeutic use of indomethacin is contraindicated in neonates with significant kidney failure.

Dietary Considerations

May cause GI upset; take with food or milk to minimize

Monitoring Parameters

Monitor response (pain, range of motion, grip strength, mobility, activities of daily living function), inflammation; observe for weight gain, edema; monitor kidney function (urine output, serum creatinine, BUN); observe for bleeding, bruising; evaluate GI effects (abdominal pain, bleeding, dyspepsia); mental confusion, disorientation, CBC, BP, LFTs (particularly with pediatric use); periodic ophthalmologic exams with prolonged therapy

Tocolysis (off-label use): Monitor for oligohydramnios and in utero constriction of the fetal ductus arteriosus if therapy continues >48 hours (ACOG 171 2016).

Mechanism of Action

Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties

Other proposed mechanisms not fully elucidated (and possibly contributing to the anti-inflammatory effect to varying degrees), include inhibiting chemotaxis, altering lymphocyte activity, inhibiting neutrophil aggregation/activation, and decreasing proinflammatory cytokine levels.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: ~30 minutes

Duration: 4 to 6 hours

Absorption: Oral: Immediate release: Neonates: Formulation specific; Adults: Prompt and extensive; Extended release: Adults: 90% over 12 hours (Note: 75 mg product is designed to initially release 25 mg and then 50 mg over an extended period of time)

Distribution: Crosses blood-brain barrier; Neonates: PDA: 0.36 L/kg; Post-PDA closure: 0.26 L/kg; Adults: 0.34-1.57 L/kg

Protein binding: 99%

Metabolism: Hepatic; significant enterohepatic recirculation; metabolites include desmethyl, desbenzoyl and desmethyl-desbenzoyl (all in unconjugated form)

Bioavailability:

Neonates, premature: Percent bioavailability reported in the literature is highly variable and may be influenced by formulation components and indomethacin physicochemical properties (Scanlon 1982); some have suggested that aqueous formulations are less bioavailable compared to ethanol based formulations (Mrongovious 1982; Scanlon 1982); aqueous suspension (in saline): 13% to 20% (Mrongovious 1982; Sharma 2003); ethanol based (96% v/v) suspension: 98.6% (Al Za'abi 2007)

Adults: Oral: 100%; rectal: 80% to 90% (than that absorbed from capsule form)

Half-life elimination:

Neonates: Postnatal age (PNA) <2 weeks: ∼20 hours; PNA >2 weeks: ∼11 hours

Adults: 2.6-11.2 hours; 7.6 hours (Tivorbex)

Time to peak: Oral: Immediate release: 2 hours; Tivorbex capsules: 1.67 hours

Excretion: Urine (60%, primarily as glucuronide conjugates); feces (33%, primarily as metabolites; 1.5% as unchanged drug)

Clearance: Preterm neonates: ~19 mL/hour/kg (range: 4.7-45.5 mL/hour/kg) (Al Za'abi 2007)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Bonidon | Confortid | Indocid | Indogesic | Indolag | Indomethacin | Indylon | Metacen | Methacin | Rothacin;
  • (AR) Argentina: Agilex | Im 75 montpellier | Indocid | Indogesic | Indometacina lafedar | Indotex | Klonametacina;
  • (AT) Austria: Amuno | Indobene | Indocid | Indohexal | Indomelan;
  • (AU) Australia: Arthrexin | Indocid | Indomethacin Agila | Indoptol;
  • (BD) Bangladesh: Imet | Incin | Indo-A | Indocap | Indocid | Indocin | Indofex | Indomet | Indomin | Indorex | Indoseem | Indotec | Indylon | Methacin | Methocid | Reumacap | Reumacid | Rheumet | Rindocin | Servimeta;
  • (BE) Belgium: Dolcidium | Indocid | Indoptol;
  • (BR) Brazil: Indocid | Indocid colirio | Metacidil;
  • (CH) Switzerland: Confortid | Indocid | Indometacin Helvepharm;
  • (CI) Côte d'Ivoire: Idol;
  • (CN) China: Indomethacin | Jupocin | Xiao yan tong;
  • (CO) Colombia: Indoblan | Indocid | Indocierr | Indomet | Indometacina | Pexail | Servimeta;
  • (CZ) Czech Republic: Apo indomethacin | Confortid | Indobene | Indocid | Indometacinum | Indomethacin | Metindol;
  • (DE) Germany: Amuno | Confortid | Durametacin | Indo | Indo paed | Indo phlogont | Indohexal | Indomet | Indometacin Sandoz | Indometacinum | Indomisal | Indorektal;
  • (DO) Dominican Republic: Indocid | Indolgina | Indotero | Malival;
  • (EC) Ecuador: Bonidon | Indocid;
  • (EE) Estonia: Indocid | Indomet | Indometacin Actavis | Indometacine cf | Indometatsiin ns | Indomethacin | Indometin | Indoxen | Indylon | Liometacen | Metindol;
  • (EG) Egypt: Bonidon | Indacin | Indocid | Indomethacin | Indomin | Liometacen | Rheumacid | Rothacin;
  • (ES) Spain: Aliviosin | Artrinovo | Flogoter | Inacid | Inacid dap | Indolgina | Indonilo | Mederreumol | Reusin;
  • (ET) Ethiopia: Indol | Indomethacin;
  • (FI) Finland: Indetrit | Indocal | Indocid | Indomesal | Indometin | Inmetsin;
  • (FR) France: Ainscrid | Chrono indocid | Dolcidium | Indocid;
  • (GB) United Kingdom: Artracin | Berlind | Imbrilon | Indocid | Indocid pda | Indoflex | Indolar | Indomax | Indomethacin | Indomethacin berk | Indomethacin boots | Indomethacin cox | Indomethacin kent | Indomod | Indotard | Kap ind | Maximet | Mobilan | Pardelprin | Rheumacin la | Rimacid | Tannex;
  • (GR) Greece: Afardin | Bavilon | Begincalm | Bonatol | Cindol | Fortathrin | Indocid | Indocid pda | Indomethol | Intobutaz | Itapredin | Reumacid | Reumadolor | Reumastop | Rheumafar;
  • (HK) Hong Kong: Apo-Indomethacine | Indocid | Indomethacin | Indoxen | Indylon | Methacin | Rheumaxin;
  • (HR) Croatia: Indometacin belupo;
  • (HU) Hungary: Indometacinum;
  • (ID) Indonesia: Areumatin | Benocid | Confortid | Dialon | Indocid | Indomethacin;
  • (IE) Ireland: Cidomel | Indocid | Indocid pda | Indolar;
  • (IL) Israel: Indomed | Indotard | Indovis;
  • (IN) India: Ancap | Artisid | Donica | Endocin-sr | Idicin | Imacin | Indocap | Indofen | Indoflam | Indogo | Indometh | Indonet | Inmecin | Inmeth | Inocin | Microcid | Recticin;
  • (IQ) Iraq: Indomethacin | Indomethacin b p;
  • (IT) Italy: Indoxen | Liometacen | Metacen;
  • (JO) Jordan: Bonidon | Indocent | Indocid | Indogesic | Indomin | Indopharm | Indorem | Indylon | Metacen | Methacin;
  • (JP) Japan: Abanyu | Aindaxin | Arsetin | Bistep | Doilin | Endsin | Idomethine | Igecin | Indacin | Indepearl | Inderanic taiyo | Inderapollon | Indome | Indometacin amel | Indometacin arax | Indometacin hexal | Indometacin hisamitsu | Indometacin hk | Indometacin isei | Indometacin maruko | Indometacin merck | Indometacin nichiiko | Indometacin r sato | Indometacin s kyorin | Indometacin s teisan | Indometacin sawai | Indometacin showa | Indometacin sioe | Indometacin sv | Indometacin takeshima | Indometacin teika | Indometacin towa | Indometacin tp | Indometacin tsuruhara | Indometacin wakodo | Indometacin yamano | Inflazon | Infree | Inmecin | Inmecin amel | Inmecin maruko | Inmecin merck hoei | Inmecin nissin | Inmecin towa | Inmetan | Inmetocin | Inpucin | Inteban | Inteban sp | Intedaru | Intedaru choseido | Intedaru kayaku | Intedaru nisshin kyorin sei | Lausit | Methalicin | Methazin sankyo | Mezolin | Mikametan | Proarisin merck hoei | Salinac | Sifolin | Taihothacin s | Zalbico;
  • (KE) Kenya: Caredomet | Cindomet | Dinlacin | Dometin | Indocid | Indomethacin | Indopac | Indos | Indosha | Indosyn | Indowin;
  • (KR) Korea, Republic of: Indocin | Indometa | Indomethacin | Inteban spansule | Intevan | Methacin | Rheumametacin;
  • (KW) Kuwait: Indocid | Rothacin;
  • (LB) Lebanon: Dolovin | Indocid | Indomel;
  • (LT) Lithuania: Indo | Indobene | Indocin | Indomelan | Indomet | Indometacin bc | Indometacine | Indotard | Metindol;
  • (LU) Luxembourg: Dolcidium | Indocid | Indomet | Indoptol;
  • (LV) Latvia: Bonidon | Indobene | Indomelan | Indomet | Metindol;
  • (MA) Morocco: Apo-methacine | Chrono indocid | Di Indo | Idol | Indocid | Indolan | Indopharm | Liometacen;
  • (MX) Mexico: Antalgin | Artaxol | Artilen | Biometacin | Draxil | Indanet | Indocid | Indometacina | Indometacina gi se | Indometacina Silanes | Indosan | Indotrin | Italon | Labymetacyn | Malival | Malival AP | Minudoc p | Neoleina | Stratasin;
  • (MY) Malaysia: Arthrexin | Asimet | Domicap | Ductaclose | Imc | Indecin | Indo | Indocap | Indocid | Indomen | Indometha | Indomethacin | Indomin | Indylon | Methacid | Methacin;
  • (NG) Nigeria: Athralon | Maxindo | New divine indomethacin;
  • (NL) Netherlands: Dometin | Indocid | Indometacine | Indometacine A | Indometacine flx;
  • (NO) Norway: Confortid | Indo | Indo ct | Indo paed | Indocid | Indomet | Indometacin Actavis | Indometacin crescent | Indometacine aurobindo | Indometacine cf | Indomethacin Sandoz | Indoxen;
  • (NZ) New Zealand: Arthrexin | Indocid | Indometacin Actavis | Indomethacin IV Mylan | Rheumacin;
  • (PE) Peru: Indocid | Indometacina;
  • (PH) Philippines: Indocid | Infree;
  • (PK) Pakistan: Arthrocid | Camocid | Incin | Indobid | Indomethacin | Indosone | Liometacen | Matindol | Methacid;
  • (PL) Poland: Indo paed | Indomet | Indomethacin | Liometacen | Metindol;
  • (PR) Puerto Rico: Indocin | Indomethacin;
  • (PT) Portugal: Dolovin | Indocid | Indometacina | Reumacide;
  • (PY) Paraguay: Xantomicin forte;
  • (QA) Qatar: Elmetacin | Indocid | Indogesic | Rothacin;
  • (RO) Romania: Indocid | Indometacin arena | Indometacin laropharm | Indometacin terapia | Indometacin zentiva;
  • (RU) Russian Federation: Indobene | Indometacin biosyn | Indometacin Biosyntez | Indometacin sopharma | Indomethacin | Indomin | Metindol;
  • (SA) Saudi Arabia: Confortid | Indocid | Indogesic | Indomethacin | Rothacin;
  • (SE) Sweden: Confortid;
  • (SG) Singapore: Apo-Indomethacine | Eldocid | Indo | Indocap | Indocid | Indoflam TR | Indomen | Methacin;
  • (SI) Slovenia: Indometacinum | Liometacen;
  • (SK) Slovakia: Indobene | Indocid | Indometacin Galvex | Indometacinum | Metindol;
  • (SL) Sierra Leone: Indomethacin;
  • (TH) Thailand: Ammi-indocin | Andocit | Api Pyrin | Busolon S | Cocid | Confortid | Docid | Docin | Dome | Dometa | Findo | Fob | Fob Indo C | Idc | Idomet | Incosit | Indo | Indo-q | Indocap | Indocid | Indocin | Indocit | Indogesic | Indohim | Indoin | Indoman | Indomed | Indomen | Indomet | Indometh | Indomethacin | Indono | Indostar | Indotrustman | Inflamed | Inflamet | Inmed | Inthacine | K.B. Indomethacin | Neocid | Phardomet | Pybucid | S Docid;
  • (TN) Tunisia: Chrono indocid | Indocid | Indocine | Indometacine Ips | Indomin | Indopal | Methacin | Rothacin | Tendinyl;
  • (TR) Turkey: Endol | Endosetin | Indocid | Romacid;
  • (TW) Taiwan: Antirheumatic | Cedric | Cyeda Cin | Defever | Goncid | Indalgin | Indecin | Indershin | Indetole | Indocaps | Indocid | Indocin | Indocine | Indome | Indomecin | Indomen | Indomesa | Indomethacin | Indothan | Indoy | Inpan | Intean | Inteban | Intedaru | Inthacid | Inthacin | Intocin | Kindocid | Lausit | Li Shin Ning | Methatin | Neo-Tonfonrin | Patetin | Pisulou | Referlas | Servimeta | Tenton;
  • (UA) Ukraine: Metindol | Movilon;
  • (UG) Uganda: Indol | Indoren | Indos | Indosupp | Rectin;
  • (UY) Uruguay: Artrilona S | Indoartril | Indocid | Indometacina Winpharm | Indopert LA | Sinartril;
  • (VE) Venezuela, Bolivarian Republic of: Cevimin | Indocid | Indometacina | Romazulan;
  • (ZA) South Africa: Adco-indomethacin | Aflamin | Amdocin | Arthrexin | Aspen-Indomethacin | Betacin | Flamaret | Flamecid | Gulf Indomethacin | Indocid | Indomethacin | Indomethacin oethmaan | Methamax | Methocaps | Nisaid | Restameth-sr | Rolab-indomethacin;
  • (ZM) Zambia: Arthrexin | Cindomet | Flamcid | Indoflam | Indomethacin | Indosule | Methocid | Recticin | Tissop;
  • (ZW) Zimbabwe: Arthrexin | Indomethacin | Methocid
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