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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(in doe METH a sin)
Generic Available (U.S.)
Yes: Excludes oral suspension
Index Terms
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088612.pdf, must be dispensed with this medication.
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Acute gouty arthritis, acute bursitis/tendonitis, moderate-to-severe osteoarthritis, rheumatoid arthritis, ankylosing spondylitis; I.V. form used as alternative to surgery for closure of patent ductus arteriosus in neonates
Use: Unlabeled/Investigational
Management of preterm labor
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events have been observed in animal reproduction studies; therefore, the manufacturer classifies indomethacin as pregnancy category C. Indomethacin crosses the placenta and can be detected in fetal plasma and amniotic fluid. Indomethacin exposure during the first trimester is not strongly associated with congenital malformations; however, cardiovascular anomalies and cleft palate have been observed following NSAID exposure in some studies. The use of an NSAID close to conception may be associated with an increased risk of miscarriage. Nonteratogenic effects have been observed following NSAID administration during the third trimester, including myocardial degenerative changes, prenatal constriction of the ductus arteriosus, failure of the ductus arteriosus to close postnatally, and fetal tricuspid regurgitation; renal dysfunction or failure, oligohydramnios; gastrointestinal bleeding or perforation, increased risk of necrotizing enterocolitis; intracranial bleeding (including intraventricular hemorrhage), platelet dysfunction with resultant bleeding; and pulmonary hypertension. The risk of fetal ductal constriction following maternal use of indomethacin is increased with gestational age and duration of therapy. Because they may cause premature closure of the ductus arteriosus, use of NSAIDs late in pregnancy should be avoided (use after 31 or 32 weeks gestation is not recommended by some clinicians). Indomethacin has been used in the management of preterm labor. Indomethacin should be used with caution in pregnant women with hypertension. The chronic use of NSAIDs in women of reproductive age may be associated with infertility that is reversible upon discontinuation of the medication.
Lactation
Enters breast milk/not recommended (AAP rates "compatible"; AAP 2001 update pending)
Breast-Feeding Considerations
Indomethacin is excreted into breast milk and low amounts have been measured in the plasma of nursing infants. Seizures in a nursing infant were observed in one case report, although adverse events have not been noted in other cases. Breast-feeding is not recommended by the manufacturer. (The therapeutic use of indomethacin is contraindicated in neonates with significant renal failure.) Hypertensive crisis and psychiatric side effects have been noted in case reports following use of indomethacin for analgesia in postpartum women. Use with caution in nursing women with hypertensive disorders of pregnancy or pre-existing renal disease.
Contraindications
Hypersensitivity to indomethacin, aspirin, other NSAIDs, or any component of the formulation; perioperative pain in the setting of coronary artery bypass graft (CABG) surgery; patients with a history of proctitis or recent rectal bleeding (suppositories)
Neonates: Necrotizing enterocolitis; impaired renal function; active bleeding (including intracranial hemorrhage and gastrointestinal bleeding), thrombocytopenia, coagulation defects; untreated infection; congenital heart disease where patent ductus arteriosus is necessary
Warnings/Precautions
Boxed warnings:
• Cardiovascular events: See “Concerns related to adverse effects” below.
• Coronary artery bypass graft surgery: See “Disease-related concerns” below.
• Gastrointestinal events: See“Concerns related to adverse effects” below.
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. Do not use in patients who experience bronchospasm, asthma, rhinitis, or urticaria with NSAID or aspirin therapy.
• Cardiovascular events: [U.S. Boxed Warning]: NSAIDs are associated with an increased risk of adverse cardiovascular thrombotic events, including MI and stroke. Risk may be increased with duration of use or pre-existing cardiovascular risk factors or disease. Carefully evaluate individual cardiovascular risk profiles prior to prescribing. Use caution with fluid retention. Avoid use in heart failure. Concurrent administration of ibuprofen, and potentially other nonselective NSAIDs, may interfere with aspirin's cardioprotective effect. 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 which require mental alertness (eg, operating machinery or driving). Discontinue use with blurred or diminished vision and perform ophthalmologic exam. Periodically evaluate vision in all patients receiving long term therapy.
• Gastrointestinal events: [U.S. Boxed Warning]: NSAIDs may increase risk of gastrointestinal irritation, inflammation, ulceration, bleeding, and perforation. These events may occur at any time during therapy and without warning. Use caution with a history of GI disease (bleeding or ulcers), concurrent therapy with aspirin, anticoagulants and/or corticosteroids, smoking, use of alcohol, the elderly 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 ≤325 mg of aspirin, a substantial increase in the risk of gastrointestinal 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).
• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE-inhibitors). Monitor potassium closely.
• Skin reactions: NSAIDs may cause serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); discontinue use at first sign of skin rash or hypersensitivity.
• Visual disturbances: Prolonged use may cause corneal deposits and retinal disturbances; discontinue if visual changes are observed.
Disease-related concerns:
• Asthma: Do not administer to patients with aspirin-sensitive asthma; severe bronchospasm may occur. Use caution in patients with other forms of asthma.
• Coronary artery bypass graft surgery: [U.S. Boxed Warning]: Use is contraindicated for treatment of perioperative pain 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 decreased hepatic function. Closely monitor patients with any abnormal LFT. Severe hepatic reactions (eg, fulminant hepatitis, liver failure) have occurred with NSAID use, rarely; discontinue if signs or symptoms of liver disease develop, or if systemic manifestations occur.
• Hypertension: Use with caution; may cause new-onset hypertension or worsening of existing hypertension.
• Parkinsonism: Use caution with Parkinson's disease; use may aggravate this condition.
• Renal impairment: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation. Patients with impaired renal function, dehydration, heart failure, liver dysfunction, those taking diuretics, and ACE inhibitors, and the elderly are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Not recommended for use in patients with advanced renal disease. Long-term NSAID use may result in renal papillary necrosis.
Special populations:
• Elderly: The elderly are at increased risk for adverse effects (especially peptic ulceration, CNS effects, renal toxicity) from NSAIDs even at low doses. Risk of CNS adverse events may be higher with indomethacin compared to other NSAIDs; avoid use in this age group (Beers Criteria).
• Pediatrics: Oral: Safety and efficacy have not been established in children <14 years of age. Hepatotoxicity has been reported in younger children treated for juvenile idiopathic arthritis (JIA). Closely monitor if needed in children ≥2 years of age.
Other warnings/precautions:
• Surgical/dental procedures: Withhold for at least 4-6 half-lives prior to surgical or dental procedures.
Adverse Reactions
>10%: Central nervous system: Headache (12%)
1% to 10%:
Central nervous system: Dizziness (3% to 9%), depression (<3%), fatigue (<3%), malaise (<3%), somnolence (<3%), vertigo (<3%)
Gastrointestinal: Dyspepsia (3% to 9%), epigastric pain (3% to 9%), heartburn (3% to 9%), indigestion (3% to 9%), nausea (3% to 9%), abdominal pain/cramps/distress (<3%), constipation (<3%), diarrhea (<3%), rectal irritation (suppository), tenesmus (suppository), vomiting
Otic: Tinnitus (<3%)
<1%: Acute respiratory distress, agranulocytosis, allergic reactions, allergic rhinitis, anaphylaxis, anemia, angiitis, angioedema, anorexia, anxiety, aplastic anemia, arrhythmia, aseptic meningitis, asthma, bloating, blurred vision, bone marrow suppression, breast enlargement, breast tenderness, bronchospasm, BUN increased, chest pain, CHF, cholestatic jaundice, coma, confusion, conjunctivitis, corneal opacities, cystitis, deafness, depersonalization, depression, diplopia, disseminated intravascular coagulation (DIC), drowsiness, dry eyes, dysarthria, dyspnea, ecchymosis, edema, epistaxis, erythema multiforme, erythema nodosum, exfoliative dermatitis, fatigue, fever, flatulence, fluid retention, flushing, hair loss, gastric perforation (rare), gastritis, GI bleeding, GI ulceration, glucosuria, gynecomastia, hearing decreased, hematuria, hemolytic anemia, hepatitis (including fatal cases), hot flashes, hyperglycemia, hyper-/hypotension, hyperkalemia, hypersensitivity reactions, insomnia, interstitial nephritis, intestinal strictures, involuntary muscle movements, itching, leukopenia, lightheadedness, necrotizing fasciitis, nephrotic syndrome, nervousness, oliguria, palpitation, paresthesia, parkinson's exacerbation, peptic ulcer, peripheral neuropathy, petechiae, polydipsia, polyuria, proctitis, proteinuria, pruritus, psychic disturbances, psychosis, pulmonary edema, purpura, rash, rectal bleeding, renal failure, renal insufficiency, retinal/macular disturbances, seizure exacerbation, shock, somnolence, Stevens-Johnson syndrome, stomatitis, sweating, syncope, tachycardia, thrombocytopenia, thrombocytopenic purpura, thrombophlebitis, toxic amblyopia, toxic epidermal necrolysis, ulcerative stomatitis, urinary frequency, urticaria, vaginal bleeding, weakness, weight gain
Metabolism/Transport Effects
Substrate (minor) of CYP2C9, 2C19; Inhibits CYP2C9 (strong), 2C19 (weak)
Drug Interactions
ACE 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 ACE Inhibitors. Risk C: Monitor therapy
Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. 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
Anticoagulants: Antiplatelet Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Anticoagulants: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antidepressants (Tricyclic, Tertiary Amine): May enhance the antiplatelet effect of NSAID (Nonselective). Risk C: Monitor therapy
Antiplatelet Agents: May enhance the anticoagulant effect of other Antiplatelet Agents. Risk C: Monitor therapy
Antiplatelet Agents: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy
Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Risk D: Consider therapy modification
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
Collagenase (Systemic): Antiplatelet Agents 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 NSAID (Nonselective). Risk C: Monitor therapy
CycloSPORINE: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE. Risk D: Consider therapy modification
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). Risk D: Consider therapy modification
Dasatinib: May enhance the anticoagulant effect of Antiplatelet Agents. 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
Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Digoxin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin. Risk C: Monitor therapy
Drotrecogin Alfa: Antiplatelet Agents may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Management: When possible, avoid use of drotrecogin within 7 days of use of any IIb/IIIa antagonists, higher dose aspirin (more than 650 mg/day), or use of other antiplatelet agents. 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
Glucosamine: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Haloperidol: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Haloperidol. Specifically including drowsiness and confusion. Risk C: Monitor therapy
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Antiplatelet Agents. Bleeding may occur. Risk D: Consider therapy modification
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Management: Concomitant treatment with these agents should generally be avoided. If used concomitantly, increased diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds) must be employed. Risk D: Consider therapy modification
HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Risk C: Monitor therapy
Ibritumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Ketorolac: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Ketorolac (Nasal): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Ketorolac (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. Risk D: Consider therapy modification
Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Risk C: Monitor therapy
Methotrexate: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Methotrexate. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of other Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Omega-3-Acid Ethyl Esters: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
PEMEtrexed: NSAID (Nonselective) may increase the serum concentration of PEMEtrexed. Management: Patients with mild-to-moderate renal insufficiency (CrCl 45-79 mL/minute) may use ibuprofen with caution, but should avoid other NSAIDs for 2-5 days prior to, the day of, and 2 days after pemetrexed. Risk D: Consider therapy modification
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Antiplatelet Agents. 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 Antiplatelet Agents. 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: Closely monitor for increased pralatrexate serum levels and/or toxicity if used concomitantly with an NSAID. Monitor for decreased pralatrexate serum levels with NSAID discontinuation. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Quinolone Antibiotics: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolone Antibiotics. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolone Antibiotics. Risk C: Monitor therapy
Salicylates: NSAID (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. NSAID (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of NSAID (Nonselective). Exceptions: Choline Magnesium Trisalicylate. Risk D: Consider therapy modification
Salicylates: Antiplatelet Agents may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). NSAID (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider using alternative analgesics, when appropriate, and/or addition of an gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Risk D: Consider therapy modification
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). Risk C: Monitor therapy
Sodium Phosphates: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with NSAIDs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Risk D: Consider therapy modification
Thiazide Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Thrombolytic Agents: Antiplatelet Agents may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Thrombolytic Agents: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. 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
Tositumomab and Iodine I 131 Tositumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Risk C: Monitor therapy
Treprostinil: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Risk C: Monitor therapy
Triamterene: Indomethacin may enhance the nephrotoxic effect of Triamterene. Management: Consider alternatives to concomitant treatment with triamterene and indomethacin. If the combination cannot be avoided, monitor for development of renal failure. Risk D: Consider therapy modification
Vancomycin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): NSAID (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may enhance gastric mucosal irritation).
Food: Food may decrease the rate but not the extent of absorption. Indomethacin peak serum levels may be delayed if taken with food.
Herb/Nutraceutical: Avoid alfalfa, anise, bilberry, bladderwrack, bromelain, cat's claw, celery, chamomile, coleus, cordyceps, dong quai, evening primrose, fenugreek, feverfew, garlic, ginger, ginkgo biloba, ginseng (American, Panax, Siberian), grapeseed, green tea, guggul, horse chestnut seed, horseradish, licorice, prickly ash, red clover, reishi, SAMe (S-adenosylmethionine), sweet clover, turmeric, white willow (all have additional antiplatelet activity).
Storage
I.V.: Store below 30°C (86°F). Protect from light.
Reconstitution
Reconstitute with 1-2 mL preservative free NS or SWFI just prior to administration. Discard any unused portion. Do not use preservative-containing diluents for reconstitution.
Compatibility
Stable in NS.
Y-site administration: Compatible: Furosemide, insulin (regular), potassium chloride, sodium bicarbonate, sodium nitroprusside. Incompatible: Amino acid injection, calcium gluconate, cimetidine, dobutamine, dopamine, gentamicin, levofloxacin, tobramycin, tolazoline. Variable (consult detailed reference): Dextrose injection.
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.
Pharmacodynamics/Kinetics
Onset of action: ~30 minutes
Duration: 4-6 hours
Absorption: Oral: Immediate release: Prompt and extensive; Extended release: 90% over 12 hours
Distribution: Vd: 0.34-1.57 L/kg; crosses blood brain barrier
Protein binding: 99%
Metabolism: Hepatic; significant enterohepatic recirculation
Bioavailability: 100%
Half-life elimination: 4.5 hours; prolonged in neonates
Time to peak: Oral: Immediate release: 2 hours
Excretion: Urine (60%, primarily as glucuronide conjugates); feces (33%, primarily as metabolites)
Dosage
Patent ductus arteriosus:
Neonates: I.V.: Initial: 0.2 mg/kg, followed by 2 doses depending on postnatal age (PNA):
PNA at time of first dose <48 hours: 0.1 mg/kg at 12- to 24-hour intervals
PNA at time of first dose 2-7 days: 0.2 mg/kg at 12- to 24-hour intervals
PNA at time of first dose >7 days: 0.25 mg/kg at 12- to 24-hour intervals
In general, may use 12-hour dosing interval if urine output >1 mL/kg/hour after prior dose; use 24-hour dosing interval if urine output is <1 mL/kg/hour but >0.6 mL/kg/hour; doses should be withheld if patient has oliguria (urine output <0.6 mL/kg/hour) or anuria
Inflammatory/rheumatoid disorders: Oral: Use lowest effective dose.
Children ≥2 years: 1-2 mg/kg/day in 2-4 divided doses; maximum dose: 4 mg/kg/day; not to exceed 150-200 mg/day
Adults: 25-50 mg/dose 2-3 times/day; maximum dose: 200 mg/day; extended release capsule should be given on a 1-2 times/day schedule (maximum dose for extended release: 150 mg/day). In patients with arthritis and persistent night pain and/or morning stiffness may give the larger portion (up to 100 mg) of the total daily dose at bedtime.
Bursitis/tendonitis: Oral: Adults: Initial dose: 75-150 mg/day in 3-4 divided doses or 1-2 divided doses for extended release; usual treatment is 7-14 days
Acute gouty arthritis: Oral: Adults: 50 mg 3 times daily until pain is tolerable then reduce dose; usual treatment <3-5 days
Elderly: Refer to adult dosing. Use lowest recommended dose and frequency in elderly to initiate therapy for indications listed in adult dosing.
Dosage adjustment in renal impairment: Not recommended in patients with advanced renal disease
Administration: Oral
Administer with food, milk, or antacids to decrease GI adverse effects. Extended release capsules must be swallowed whole; do not crush.
Administration: I.V.
Administer over 20-30 minutes. Reconstitute I.V. formulation just prior to administration; discard any unused portion; avoid I.V. bolus administration or 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. Do not administer intra-arterially.
Administration: I.V. Detail
pH: 6.0-7.5
Monitoring Parameters
Monitor response (pain, range of motion, grip strength, mobility, ADL function), inflammation; observe for weight gain, edema; monitor renal function (serum creatinine, BUN); observe for bleeding, bruising; evaluate gastrointestinal effects (abdominal pain, bleeding, dyspepsia); mental confusion, disorientation, CBC, liver function tests (particularly with pediatric use); ophthalmologic exams with prolonged therapy
Test Interactions
False-negative dexamethasone suppression test
Dietary Considerations
May cause GI upset; take with food or milk to minimize
Patient Education
Do not crush, break, or chew extended-release capsules. Take with food or milk to reduce GI distress. Maintain adequate hydration, unless instructed to restrict fluid intake. May cause drowsiness, dizziness, nervousness, headache, anorexia, nausea, vomiting, heartburn, or fluid retention (weigh yourself weekly and report unusual weight gain). GI bleeding, ulceration, or perforation can occur with or without pain; discontinue medication and contact prescriber if persistent abdominal pain or cramping or blood in stool occurs. Report difficult breathing or unusual cough; chest pain, rapid heartbeat, or palpitations; unusual bruising or bleeding; blood in urine, gums, or vomitus; swollen extremities; skin rash, irritation, or itching; acute persistent fatigue; vision changes; or ringing in ears.
Geriatric Considerations
Elderly are a high-risk population for adverse effects from NSAIDs. As much as 60% of elderly can develop peptic ulceration and/or hemorrhage asymptomatically. The concomitant use of H2 blockers and sucralfate is not effective as prophylaxis with the exception of NSAID-induced duodenal ulcers which may be prevented by the use of ranitidine. Misoprostol and proton pump inhibitors are the only agents proven to help prevent the development of NSAID-induced ulcers. Also, concomitant disease and drug use contribute to the risk for GI adverse effects. Use lowest effective dose for shortest period possible. Consider renal function decline with age. Use of NSAIDs may compromise existing renal function especially when Clcr is ≤30 mL/minute. Tinnitus may be a difficult and unreliable indication of toxicity due to age-related hearing loss or eighth cranial nerve damage. CNS adverse effects such as confusion, agitation, and hallucination are generally seen in overdose or high-dose situations, but the elderly may demonstrate these adverse effects at lower doses than younger adults. Indomethacin frequently causes confusion at recommended doses in the elderly.
This medication is considered to be potentially inappropriate in this patient population (Beers Criteria severity: High).
Anesthesia and Critical Care Concerns/Other Considerations
The 2002 ACCM/SCCM guidelines for analgesia (critically-ill adult) suggest that NSAIDs may be used in combination with opioids in select patients for pain management. Concern about adverse events (increased risk of renal dysfunction, altered platelet function and gastrointestinal irritation) limits its use in patients who have other underlying risks for these events.
In short-term use, NSAIDs vary considerably in their effect on blood pressure. When NSAIDs are used in patients with hypertension, appropriate monitoring of blood pressure responses should be completed and the duration of therapy, when possible, kept short. The use of NSAIDs in the treatment of patients with congestive heart failure may be associated with an increased risk for fluid accumulation and edema; may precipitate renal failure in dehydrated patients.
Cardiovascular Considerations
Blood Pressure: In short-term use, NSAIDs vary considerably in their effect on blood pressure. A recent meta-analysis (see References) showed that indomethacin and naproxen had the largest effect on blood pressure. Other NSAIDs, including piroxicam, ibuprofen, and sulindac had less of an effect. Ibuprofen combined with captopril or losartan may attenuate the antihypertensive effects of ACE inhibition or receptor blockade on sitting or 24-hour ambulatory diastolic blood pressure. When NSAIDs are used in patients with hypertension, appropriate monitoring of blood pressure responses should be completed and the duration of therapy, when possible, kept short.
Heart Failure: The use of NSAIDs in the treatment of patients with heart failure may be associated with an increased risk for fluid accumulation and edema. One study showed that NSAID use in elderly patients had an increased risk of hospitalization for heart failure. This study gives compelling reasons to avoid or limit the use of NSAIDs in patients with heart failure, particularly in the elderly population. The ACC/AHA 2009 heart failure guidelines suggest that NSAIDs be avoided or withdrawn whenever possible in patients with current or prior symptoms of heart failure and reduced LVEF.
Risk of Cardiovascular Events: Patients at increased risk of cardiovascular adverse events include patients immediately postoperative (10-14 days) from CABG surgery, and those with existing CAD, CVD, or history of TIA. Prescribers are encouraged to use the lowest effective dose for the shortest duration of time based on individual patient treatment goals. Available evidence reviewed by the FDA does not suggest an increased risk of serious CV events when NSAIDs are given short term and in the lower doses used OTC.
Drug Interactions: Nonsteroidal anti-inflammatory agents, including ibuprofen and naproxen, may diminish the cardioprotective effect of aspirin (Catella-Lawson F, 2001; Capone ML, 2005). It is surmised that ibuprofen may exhibit greater affinity than aspirin for the COX-1 site or if dosed regularly (or prior to aspirin), it would gain access to the active site first. In either case, aspirin's inhibition of COX (irreversible) would be limited in favor of ibuprofen inhibition (reversible). Avoid regular use of NSAIDs (nonselective) if possible. If used occasionally, take after aspirin (immediate release) ingestion.
Dental Health: Effects on Dental Treatment
The dentist should be aware of the potential of abnormal coagulation. Caution should also be exercised in the use of NSAIDs in patients already on anticoagulant therapy with drugs such as warfarin (Coumadin®). See Effects on Bleeding.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness is common; may cause nervousness; may rarely cause sedation, confusion, depression, and hallucinations
Mental Health: Effects on Psychiatric Treatment
May cause bone marrow suppression; use caution with clozapine and carbamazepine; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels
Nursing: Physical Assessment/Monitoring
Evaluate cardiac risk and potential for GI bleeding prior to prescribing this medication. Monitor blood pressure prior to treatment and periodically throughout. Regular ophthalmic evaluations are recommended.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral: 25 mg, 50 mg
Capsule, extended release, oral: 75 mg
Injection, powder for reconstitution: 1 mg
Indocin® I.V.: 1 mg
Suppository, rectal: 50 mg (30s)
Suspension, oral:
Indocin®: 25 mg/5 mL (237 mL) [contains ethanol 1%; pineapple-coconut-mint flavor]
Pricing: U.S. (www.drugstore.com)
Capsule, controlled release (Indomethacin CR)
75 mg (30): $82.15
Capsules (Indomethacin)
25 mg (30): $15.99
50 mg (30): $15.99
References
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Jacobi J, Fraser GL, Coursin DB, et al, “Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult,” Crit Care Med, 2002, 30(1):119-41. Available at http://www.sccm.org/pdf/sedatives.pdf. Accessed August 2, 2003.
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International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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