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Look Up > Drugs > Indomethacin
Indomethacin
Pronunciation
U.S. Brand Names
Generic Available
Canadian Brand Names
Synonyms
Pharmacological Index
Use
Pregnancy Risk Factor
Contraindications
Warnings/Precautions
Adverse Reactions
Overdosage/Toxicology
Drug Interactions
Stability
Mechanism of Action
Pharmacodynamics/Kinetics
Usual Dosage
Dietary Considerations
Monitoring Parameters
Test Interactions
Mental Health: Effects on Mental Status
Mental Health: Effects on Psychiatric Treatment
Dental Health: Local Anesthetic/Vasoconstrictor Precautions
Dental Health: Effects on Dental Treatment
Patient Information
Nursing Implications
Dosage Forms
References

Pronunciation
(in doe METH a sin)

U.S. Brand Names
Indochron E-R®; Indocin®; Indocin® I.V.; Indocin® SR

Generic Available

Yes


Canadian Brand Names
Apo®-Indomethacin; Indocid®; Indocid® SR; Novo-Methacin; Nu-Indo; Pro-Indo®

Synonyms
Indometacin; Indomethacin Sodium Trihydrate

Pharmacological Index

Nonsteroidal Anti-Inflammatory Agent (NSAID)


Use

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


Pregnancy Risk Factor

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


Contraindications

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


Warnings/Precautions

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.


Adverse Reactions

>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


Overdosage/Toxicology

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.


Drug Interactions

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)


Stability

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


Mechanism of Action

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


Pharmacodynamics/Kinetics

Onset of action: Within 30 minutes

Duration: 4-6 hours

Absorption: Prompt and extensive

Distribution: Vd: 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


Usual Dosage

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


Dietary Considerations

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.


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


Test Interactions

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


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


Dental Health: Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions


Dental Health: Effects on Dental Treatment

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®).


Patient Information

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.


Nursing Implications

Extended release capsules must be swallowed intact


Dosage Forms

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)


References

Brooks PM and Day RO, "Nonsteroidal Anti-inflammatory Drugs - Differences and Similarities," N Engl J Med, 1991, 324(24):1716-25.

Clinch D, Banerjee AK, Ostick G, "Absence of Abdominal Pain in Elderly Patients With Peptic Ulcer," Age Ageing, 1984, 13:120-3.

Clive DM, Stoff JS, "Renal Syndromes Associated With Nonsteroidal Anti-inflammatory Drugs," N Engl J Med, 1984, 310(9):563-72.

Coombs RC, Morgan ME, Durbin GM, et al, "Gut Blood Flow Velocities in the Newborn: Effects of Patent Ductus Arteriosus and Parenteral Indomethacin," Arch Dis Child, 1990, 65(10 Spec No):1067-71.

Court H and Volans GN, "Poisoning After Overdose With Nonsteroidal Anti-inflammatory Drugs," Adverse Drug React Acute Poisoning Rev, 1984, 3(1):1-21.

Gersony WM, Peckham GJ, Ellison RC, et al, "Effects of Indomethacin in Premature Infants With Patent Ductus Arteriosus: Results of a National Collaborative Study," J Pediatr, 1983, 102(6):895-906.

Graham DY, "Prevention of Gastroduodenal Injury Induced by Chronic Nonsteroidal Anti-inflammatory Drug Therapy," Gastroenterology, 1989, 96(2 Pt 2 Suppl):675-81.

Gurwitz JH, Avorn J, Ross-Degnan D, et al, "Nonsteroidal Anti-Inflammatory Drug-Associated Azotemia in the Very Old," JAMA, 1990, 264(4):471-5.

Hawkey CJ, Karrasch JA, Szczepanski L, et al, "Omeprazole Compared With Misoprostrol for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs," N Engl J Med, 1998, 338(11):727-34.

Hoppmann RA, Peden JG, and Ober SK, "Central Nervous System Side Effects of Nonsteroidal Anti-inflammatory Drugs. Aseptic Meningitis, Psychosis, and Cognitive Dysfunction," Arch Intern Med, 1991, 151(7):1309-13.

Kraus DM and Hatzopoulos FK, "Neonatal Therapy," Applied Therapeutics: The Clinical Use of Drugs, 6th ed, Young LY, Koda-Kimble MA, eds, Vancouver, WA: Applied Therapeutics, Inc, 1995.

Pounder R, "Silent Peptic Ulceration: Deadly Silence or Golden Silence?" Gastroenterology, 1989, 96(2 Pt 2 Suppl):626-31.

Sheehan TM, Boldy DA, and Vale JA, "Indomethacin Poisoning," J Toxicol Clin Toxicol, 1986, 24(2):151-8.

Smolinske SC, Hall AH, Vandenberg SA, et al, "Toxic Effects of Nonsteroid Anti-inflammatory Drugs in Overdose. An Overview of Recent Evidence on Clinical Effects and Dose-Response Relationships," Drug Saf, 1990, 5(4):252-74.

The International Agranulocytosis and Aplastic Anemia Study, "Risks of Agranulocytosis and Aplastic Anemia. A First Report of Their Relation to Drug Use With Special Reference to Analgesics," JAMA, 1986, 256(13):1749-57.

Vale JA and Meredith TJ, "Acute Poisoning Due to Nonsteroidal Anti-inflammatory Drugs," Med Toxicol, 1986, 1(1):12-31.

Verbeeck RK, "Pharmacokinetic Drug Interactions With Nonsteroidal Anti-inflammatory Drugs," Clin Pharmacokinet, 1990, 19(1):44-66.

Wong F, Massie D, and Hsu P, "The Effect of Misoprostol on Indomethacin-Induced Renal Dysfunction in Well-Compensated Cirrhosis," J Hepatol, 1995, 23(1):1-7.

Yeomans ND, Tulassay Z, Juhasz L, et al, "A Comparison of Omeprazole With Ranitidine for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs," N Engl J Med, 1998, 338(11):719-26.


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