Pronunciation:

(in doe METH a sin)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Pregnancy Risk Factor:

Lactation:

Contraindications:

Warnings/Precautions:

Use of NSAIDs can compromise existing renal function especially when Clcr<30 mL/minute. CNS adverse effects such as confusion, agitation, and hallucination are generally seen in overdose or high-dose situations; however, elderly may demonstrate these adverse effects at lower doses than younger adults. 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%), drowsiness (<1%), fatigue (<3%), vertigo (<3%), depression (<3%), malaise (<3%), somnolence (<3%)

Gastrointestinal: Nausea (3% to 9%), epigastric pain (3% to 9%), abdominal pain/cramps/distress (<3%), anorexia (<1%), GI bleeding (<1%), ulcers (<1%), perforation (<1%), heartburn (3% to 9%), indigestion (3% to 9%), constipation (<3%), diarrhea (<3%), dyspepsia (3% to 9%)

Hematologic: Inhibition of platelet aggregation (3% to 9%)

Otic: Tinnitus (<3%)

<1%: Acute respiratory distress, agranulocytosis, allergic rhinitis, anaphylaxis, anemia, angioedema, anorexia, arrhythmia, aseptic meningitis, asthma, blurred vision, bone marrow suppression, bronchospasm, cholestatic jaundice, confusion, CHF, conjunctivitis, corneal opacities, cystitis, decreased hearing, depression, dilutional hyponatremia (I.V.), drowsiness, dry eyes, dyspnea, epistaxis, erythema multiforme, exfoliative dermatitis, fatigue, flatulence, gastritis, GI ulceration, hallucinations, hemolytic anemia, hepatitis (including fatal cases), hot flashes, hyperkalemia, hypersensitivity reactions, hypertension, hypoglycemia (I.V.), interstitial nephritis, itching, leukopenia, nephrotic syndrome, oliguria, peripheral neuropathy, polydipsia, polyuria, proctitis, psychic disturbances, psychosis, rash, renal failure, retinal/macular disturbances, shock, somnolence, Stevens-Johnson syndrome, stomatitis, tachycardia, thrombocytopenia, toxic amblyopia, toxic epidermal necrolysis, urticaria

Overdosage/Toxicology:

Drug Interactions:

ACE inhibitors: Antihypertensive effects may be decreased by concurrent therapy with NSAIDs; monitor blood pressure.

Angiotensin II antagonists: Antihypertensive effects may be decreased by concurrent therapy with NSAIDs; monitor blood pressure.

Anticoagulants (warfarin, heparin, LMWHs) in combination with NSAIDs can cause increased risk of bleeding.

Antiplatelet drugs (ticlopidine, clopidogrel, aspirin, abciximab, dipyridamole, eptifibatide, tirofiban) can cause an increased risk of bleeding.

Cholestyramine and colestipol reduce the bioavailability of some NSAIDs; separate administration times.

Corticosteroids may increase the risk of GI ulceration; avoid concurrent use.

Cyclosporine: NSAIDs may increase serum creatinine, potassium, blood pressure, and cyclosporine levels; monitor cyclosporine levels and renal function carefully.

CYP2C8/9 substrates: Indomethacin may increase the levels/effects of CYP2C8/9 substrates. Example substrates include amiodarone, fluoxetine, glimepiride, glipizide, nateglinide, phenytoin, pioglitazone, rosiglitazone, sertraline, and warfarin.

Gentamicin and amikacin serum concentrations are increased by indomethacin in premature infants. Results may apply to other aminoglycosides and NSAIDs.

Hydralazine's antihypertensive effect is decreased; avoid concurrent use.

Lithium levels can be increased; avoid concurrent use if possible or monitor lithium levels and adjust dose. Sulindac may have the least effect. When NSAID is stopped, lithium will need adjustment again.

Loop diuretics efficacy (diuretic and antihypertensive effect) is reduced. Indomethacin reduces this efficacy, however, it may be anticipated with any NSAID.

Methotrexate: Severe bone marrow suppression, aplastic anemia, and GI toxicity have been reported with concomitant NSAID therapy. Avoid use during moderate or high-dose methotrexate (increased and prolonged methotrexate levels). NSAID use during low-dose treatment of rheumatoid arthritis has not been fully evaluated; extreme caution is warranted.

Thiazides antihypertensive effects are decreased; avoid concurrent use.

Warfarin's INRs may be increased by piroxicam. Other NSAIDs may have the same effect depending on dose and duration. Monitor INR closely. Use the lowest dose of NSAIDs possible and for the briefest duration.

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 cat's claw, dong quai, evening primrose, feverfew, garlic, ginger, ginkgo, red clover, horse chestnut, green tea, ginseng (all have additional antiplatelet activity).

Stability:

Compatibility:

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:

Pharmacodynamics/Kinetics:

Onset of action: ~30 minutes

Duration: 4-6 hours

Absorption: Prompt and extensive

Distribution: Vd: 0.34-1.57 L/kg; crosses placenta; enters breast milk

Protein binding: 90%

Metabolism: Hepatic; significant enterohepatic recirculation

Half-life elimination: 4.5 hours; prolonged in neonates

Time to peak: Oral: ~3-4 hours

Excretion: Urine (primarily as glucuronide conjugates)

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:

Children: 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 sustained release is 150 mg/day

Elderly: Refer to Adults dosing; best to start older adults on 25 mg dose given 2-3 times/day

Administration:

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

I.V.: Administer over 20-30 minutes at a concentration of 0.5-1 mg/mL in preservative-free sterile water for injection or normal saline. 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.

Monitoring Parameters:

Test Interactions:

Dietary Considerations:

Patient Education:

Anesthesia and Critical Care Concerns/Other Considerations:

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:

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Dosage Forms:

Capsule (Indocin®): 25 mg, 50 mg

Capsule, sustained release (Indocin® SR): 75 mg

Injection, powder for reconstitution, as sodium trihydrate (Indocin® I.V.): 1 mg

Suspension, oral (Indocin®): 25 mg/5 mL (237 mL) [contains alcohol 1%; pineapple-coconut-mint flavor]

International Brand Names: