Yes

Nonsteroidal Anti-Inflammatory Agent (NSAID)

Management of inflammatory diseases and rheumatoid disorders; moderate pain; acute gouty arthritis; I.V. form used as alternative to surgery for closure of patent ductus arteriosus in neonates

B (D if used longer than 48 hours or after 34-week gestation)

Hypersensitivity to indomethacin, any component, aspirin, or other nonsteroidal anti-inflammatory drugs (NSAIDs); active GI bleeding, ulcer disease; premature neonates with necrotizing enterocolitis, impaired renal function, active bleeding, thrombocytopenia

Use with caution in patients with cardiac dysfunction, dehydration, hypertension, renal or hepatic impairment, epilepsy, history of GI bleeding, patients receiving anticoagulants, and for treatment of JRA in children (fatal hepatitis has been reported); may have adverse effects on fetus; may affect platelet and renal function in neonates; elderly are a high-risk population for adverse effects from nonsteroidal anti-inflammatory agents. As much as 60% of elderly can develop peptic ulceration and/or hemorrhage asymptomatically.

CNS adverse effects such as confusion, agitation, and hallucination are generally seen in overdose or high-dose situations; but elderly may demonstrate these adverse effects at lower doses than younger adults.

>10%:

Central nervous system: Dizziness

Dermatologic: Rash

Gastrointestinal: Nausea, epigastric pain, abdominal pain, anorexia, GI bleeding, ulcers, perforation, abdominal cramps, heartburn, indigestion

1% to 10%:

Central nervous system: Headache, nervousness

Dermatologic: Itching

Endocrine & metabolic: Fluid retention

Gastrointestinal: Vomiting

Otic: Tinnitus

<1%: Hypertension, congestive heart failure, arrhythmias, tachycardia, somnolence, fatigue, depression, confusion, drowsiness, hallucinations, aseptic meningitis, urticaria, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, hyperkalemia, dilutional hyponatremia (I.V.), hypoglycemia (I.V.), polydipsia, hot flashes, gastritis, GI ulceration, cystitis, polyuria, hemolytic anemia, bone marrow suppression, agranulocytosis, thrombocytopenia, inhibition of platelet aggregation, anemia, leukopenia, hepatitis, peripheral neuropathy, corneal opacities, blurred vision, conjunctivitis, dry eyes, toxic amblyopia, decreased hearing, oliguria, renal failure, shortness of breath, allergic rhinitis, epistaxis, hypersensitivity reactions

Symptoms of overdose include drowsiness, lethargy, nausea, vomiting, seizures, paresthesia, headache, dizziness, GI bleeding, cerebral edema, tinnitus, leukocytosis, renal failure

Management of a nonsteroidal anti-inflammatory drug (NSAID) intoxication is primarily supportive and symptomatic. Fluid therapy is commonly effective in managing the hypotension that may occur following an acute NSAID overdose, except when this is due to an acute blood loss. Seizures tend to be very short-lived and often do not require drug treatment. Although, recurrent seizures should be treated with I.V. diazepam.

CYP2C9 enzyme substrate

Increased toxicity: May increase serum potassium with potassium-sparing diuretics; probenecid may increase indomethacin serum concentrations; other NSAIDs may increase GI adverse effects; may increase nephrotoxicity of cyclosporin

Indomethacin may increase serum concentrations of digoxin, methotrexate, lithium, and aminoglycosides (reported with I.V. use in neonates)

I.V.: Protect from light; not stable in alkaline solution; reconstitute just prior to administration; discard any unused portion; do not use preservative-containing diluents for reconstitution; suppositories do not require refrigeration

Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclo-oxygenase, which results in decreased formation of prostaglandin precursors

Onset of action: Within 30 minutes

Duration: 4-6 hours

Absorption: Prompt and extensive

Distribution: V_d: 0.34-1.57 L/kg; crosses the placenta; appears in breast milk

Protein binding: 90%

Metabolism: In the liver with significant enterohepatic cycling

Half-life: 4.5 hours, longer in neonates

Time to peak serum concentration: Oral: Within 3-4 hours

Elimination: Significant enterohepatic recycling; excreted in urine principally as glucuronide conjugates

Patent ductus arteriosus: Neonates: I.V.: Initial: 0.2 mg/kg; followed with: 2 doses of 0.1 mg/kg at 12- to 24-hour intervals if age <48 hours at time of first dose; 0.2 mg/kg 2 times if 2-7 days old at time of first dose; or 0.25 mg/kg 2 times if over 7 days at time of first dose; discontinue if significant adverse effects occur. Dose should be withheld if patient has anuria or oliguria.

Analgesia:

Children: Oral: Initial: 1-2 mg/kg/day in 2-4 divided doses; maximum: 4 mg/kg/day; not to exceed 150-200 mg/day

Adults: Oral, rectal: 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

Food: May decrease the rate but not the extent of oral absorption. Drug may cause GI upset, bleeding, ulceration, perforation; take with food or milk to minimize GI upset.

Potassium: Hyperkalemia has been reported. The elderly and those with renal insufficiency are at greatest risk. Monitor potassium serum concentration in those at greatest risk. Avoid salt substitutes.

Sodium: Hyponatremia from sodium retention. Suspect secondary to suppression of renal prostaglandin. Monitor serum concentration and fluid status. May need to restrict fluid.

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

Positive direct Coombs'; increased sodium, chloride, prolonged bleeding time

Dizziness is common; may cause nervousness; may rarely cause sedation, confusion, depression, and hallucinations

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

No information available to require special precautions

NSAID formulations are known to reversibly decrease platelet aggregation via mechanisms different than observed with aspirin. 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®).

Oral: Take this medication exactly as directed; do not increase dose without consulting prescriber. Do not crush, break, or chew capsules. Take with food or milk to reduce GI distress. Maintain adequate fluid intake (2-3 L/day of fluids unless instructed to restrict fluid intake).

Rectal: Suppositories do not need to be refrigerated. Wash hands before inserting unwrapped suppository high up in rectum. Wearing glove is recommended. (Use caution to avoid damage with long fingernails.)

Do not use alcohol, aspirin, or aspirin-containing medication, and all other anti-inflammatory medications without consulting prescriber. You may experience drowsiness, dizziness, nervousness, or headache (use caution when driving or engaging in tasks requiring alertness until response to drug is known); anorexia, nausea, vomiting, or heartburn (frequent small meals, frequent oral care, sucking lozenges, or chewing gum may help); fluid retention (weigh yourself weekly and report unusual (3-5 lb/week) weight gain). May discolor stool (green). 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 breathlessness, difficulty breathing, or unusual cough; chest pain, rapid heartbeat, palpitations; unusual bruising/bleeding; blood in urine, stool, gums, or vomitus; swollen extremities; skin rash, irritation, or itching; acute fatigue; or changes in hearing or ringing in ears. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Extended release capsules must be swallowed intact

Capsule: 25 mg, 50 mg

Indocin®: 25 mg, 50 mg

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

Powder for injection, as sodium trihydrate (Indocin® I.V.): 1 mg

Suppository, rectal (Indocin®): 50 mg

Suspension, oral (Indocin®): 25 mg/5 mL (5 mL, 10 mL, 237 mL, 500 mL)

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