Indomethacin

Trade Names:Indocin IV- Powder for Injection 1 mg

Trade Names:Indocin SR- Capsules, sustained-release 75 mg

Trade Names:Indocin- Suppository 50 mg

Trade Names:Indocin- Suspension, oral 25 mg per 5 mL

Trade Names:Indomethacin- Capsules 25 mg- Capsules 50 mg

Pharmacology

Decreases fever, inflammation, and pain, probably through inhibition of cyclooxygenase activity and prostaglandin synthesis; causes closure of a patent ductus arteriosus through inhibition of prostaglandin synthesis.

Pharmacokinetics

Absorption

C _max is approximately 1 to 2 mcg/mL (dose-dependent). T _max is approximately 2 h. Bioavailability is approximately 100%.

Distribution

99% is protein bound. Crosses blood-brain barrier and placenta.

Metabolism

Undergoes appreciable enterohepatic circulation. The metabolites are desbenzoyl, desmethyl, and desmethyl-desbenzoyl.

Elimination

Eliminated via biliary excretion, metabolism, and renal excretion. The mean t _½ is approximately 4.5 h. Approximately 60% is excreted in urine and 33% in feces.

Indications and Usage

Symptomatic treatment of acute gouty arthritis (except sustained-release capsules); acute painful shoulder (bursitis and/or tendonitis) and moderate to severe ankylosing spondylitis, osteoarthritis, and rheumatoid arthritis.

Closure of patent ductus arteriosus.

Contraindications

Treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery; patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; hypersensitivity to any component of the product.

Newborns with proven or suspected untreated infection; neonates who are bleeding; neonates with thrombocytopenia, coagulation defects, necrotizing enterocolitis, significant renal function impairment, and/or congenital heart disease (eg, pulmonary atresia, severe tetralogy of Fallot, severe coarctation of the aorta).

Dosage and Administration

PO/PR 75 to 150 mg/day in divided doses for 7 to 14 days (or 75 to 150 mg sustained-release capsules 1 to 2 times daily).

PO/PR 25 mg twice daily or 3 times daily up to max of 200 mg/day (or 75 mg sustained-release capsules 1 to 2 times daily).

PO/PR 50 mg 3 times daily; do not use sustained-release capsules.

IV 3 doses total.

IV 0.2 mg/kg followed by 2 doses of 0.1 mg/kg 12 to 24 h apart.

IV 3 doses of 0.2 mg/kg separated by 12 to 24 h.

IV 0.2 mg/kg followed by 2 doses of 0.25 mg/kg separated by 12 to 24 h.

General Advice

• SR
• Sustained-release capsules should not be broken, crushed, or chewed.

• Injection
• Shake suspension before measuring dose.
• Inject solution IV. Suggested infusion rate is more than 20 to 30 min.
• Prepare IV solution with only 1 to 2 mL of preservative-free sterile sodium chloride 0.9% injection or preservative-free sterile water for injection. Discard any unused portion of the solution. If 1 mL of diluent is used, indomethacin concentration equals 0.1 mg per 0.1 mL; if 2 mL of diluent is used, indomethacin concentration equals 0.05 mg per 0.1 mL. Once reconstituted, administer immediately.

Storage/Stability

Store at 68° to 77°F. Protect from light.

Store at 59° to 86°F. Protect from moisture.

Store below 86°F. Protect from light.

Store below 86°F. Avoid temperatures above 122°F. Protect from freezing.

Store below 86°F. Avoid temperatures above 104°F.

Drug Interactions

Antihypertensive effects may be decreased.

Aminoglycoside levels may be elevated, increasing the risk of toxicity.

May increase risk of gastric erosion and bleeding.

Protein binding of indomethacin may be reduced; in addition, the risk of gastric erosion and bleeding may be increased. Concurrent use is not recommended.

Risk of cyclosporine toxicity may be increased, possibly caused by decreased synthesis of renal prostaglandin.

Diflunisal may decrease renal Cl and significantly increase indomethacin plasma concentrations that may produce toxicity. Concurrent use is not recommended.

May increase digoxin levels. Monitor levels closely.

May decrease diuretic effects. Do not administer with triamterene.

May decrease lithium Cl, resulting in toxicity.

May increase methotrexate levels.

Concurrent use of other NSAIDs is not recommended because of increased risk of GI toxicity.

Additive increase in serum potassium levels.

Plasma concentrations of indomethacin may be increased, necessitating a lower dose.

Increased risk of GI bleeding.

Laboratory Test Interactions

False-negative test results may occur in dexamethasone suppression test.

Adverse Reactions

CNS

Headache (12%); dizziness (3% to 9%); depression, fatigue, somnolence, vertigo (less than 3%).

EENT

Tinnitus (less than 3%).

GI

Dyspepsia, GI bleeding (IV only), nausea with or without vomiting (3% to 9%); abdominal distress or pain, constipation, diarrhea (less than 3%).

Metabolic

Elevated potassium, hyponatremia (3% to 9%; IV only).

Miscellaneous

Fulminating necrotizing fasciitis (particularly in association with group A beta-hemolytic streptococcus).

Precautions

Pregnancy

Category C . Avoid use in late pregnancy.

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established in children younger than 14 yr of age, except use of IV form in infants.

Elderly

Use with caution.

Renal Function

Not recommended in patients with advanced renal disease. Use with caution in patients with renal function impairment and closely monitor renal function.

Anaphylactoid reactions

Do not administer to patients with aspirin triad, which occurs typically in patients with asthma who experience rhinitis with or without nasal polyps, or patients who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs.

Asthma

Patients with asthma may have aspirin-sensitive asthma, which may be associated with severe and sometimes fatal bronchospasm. Do not administer indomethacin to patients with this type of aspirin-sensitivity because of possible cross-reactivity.

CNS effects

May aggravate depression or other psychiatric disorders, epilepsy, or Parkinsonism; use with caution.

Edema

Fluid retention and edema have been reported. Use with caution in patients with fluid retention or heart failure.

Hematologic effects

Anemia may occur, possibly caused by fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis.

Hepatic effects

Borderline elevations of 1 or more LFT may occur in patients taking indomethacin.

Hypertension

New hypertension or worsening of preexisting hypertension, either of which may contribute to increased risk of CV events, may occur.

Infection

May mask the usual signs and symptoms of infection.

Ocular effects

Corneal deposits and retinal disturbances, including those of the macula, have been reported.

Platelet function

NSAIDs inhibit platelet aggregation and have been reported to prolong bleeding time.

Renal effects

Long-term administration has resulted in renal papillary necrosis and other renal injury.

Skin reactions

Serious and sometimes fatal skin adverse reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, may occur.

Overdosage

Symptoms

Disorientation, dizziness, headache, lethargy, mental confusion, nausea, numbness, paresthesias, seizures, vomiting.

Patient Information

• Advise women of childbearing potential that use of indomethacin in late pregnancy should be avoided because of the risk of premature closure of the ductus arteriosus.
• Advise patient to discontinue drug and immediately notify health care provider if any of the following occur: black or bloody stools, bleeding or unusual bruising, changes in urine patterns, fever, flu-like symptoms, itching or skin rash, joint pain, persistent or recurrent GI upset or stomach pain, rapid weight gain or swelling, unexplained tiredness or fatigue, visual changes, vomiting blood, or yellowing of the skin or eyes.
• Advise patient to seek emergency medical assistance if any of the following occur: chest pain, shortness of breath or trouble breathing, slurred speech, swelling of the face or throat, or weakness in one part or on one side of body.
• Tell patient to take medication with antacids, food, or milk to reduce GI upset. Inform health care provider if stomach distress continues.
• Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.
• Explain that therapeutic effects for rheumatoid arthritis may not be seen for up to 1 mo of drug use.
• Explain purpose of medication and, for parents of infants with ductus arteriosus, emphasize the need for frequent monitoring.

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