INDOMETHACIN

INDOMETHACIN (in-doe-meth'a-sin) Indocid , Indocin, Indocin SR Classifications: analgesic, nonsteroidal antiinflammatory (nsaid); antipyretic; Therapeutic: nsaid, analgesic; antipyretic Prototype: Ibuprofen Pregnancy Category: B first and second trimester; D third trimester

Availability

25 mg, 50 mg capsules; 75 mg sustained release capsules; 25 mg/5 mL oral suspension; 50 mg suppositories; 1 mg injection

Action

Potent nonsteroidal compound that competes with COX-1 and COX-2 enzymes, thus interfering with formation of prostaglandin. Appears to reduce motility of polymorphonuclear leukocytes, development of cellular exudates, and vascular permeability in injured tissue resulting in its antiinflammatory effects. Inhibition of prostaglandins is thought to promote closure of the patency of the ductus arterious. Antipyretic and antiinflammatory actions may be related to its ability to inhibit prostaglandin biosynthesis.

Therapeutic Effect

It is a potent analgesic, antiinflammatory, and antipyretic agent. Promotes closure of persistent patent ductus arteriosus.

Uses

Palliative treatment in active stages of moderate to severe rheumatoid arthritis, ankylosing rheumatoid spondylitis, acute gouty arthritis, and osteoarthritis of hip in patients intolerant to or unresponsive to adequate trials with salicylates and other therapy. Also used IV to close patent ductus arteriosus in the premature infant.

Unlabeled Uses

To relieve biliary pain and dysmenorrhea, Paget's disease, athletic injuries, juvenile arthritis, idiopathic pericarditis.

Contraindications

Allergy to indomethacin, aspirin, or other NSAID; nasal polyps associated with angioedema; history of GI lesions; perioperative pain with CABG; pregnancy (category B; D in third trimester).

Cautious Use

History of psychiatric illness, epilepsy, parkinsonism; impaired renal or hepatic function; uncontrolled infections; coagulation defects, CHF; older adults, persons in hazardous occupations.

Route & Dosage

Rheumatoid Arthritis Adult: PO 25–50 mg b.i.d or t.i.d. (max: 200 mg/d) or 75 mg sustained release 1–2 times/d Pediatric Arthritis Child: PO 1–2 mg/kg/d in 2–4 divided doses (max: 4 mg/kg/d) or 150–200 mg/d Acute Gouty Arthritis Adult: PO/PR 50 mg t.i.d. until pain is tolerable, then rapidly taper Bursitis Adult: PO 25–50 mg t.i.d. or q.i.d. (max: 200 mg/d) or 75 mg sustained release 1–2 times/d Close Patent Ductus Arteriosus Premature neonate: IV <48 h, 0.2 mg/kg followed by 2 doses of 0.1 mg/kg q12–24h; 2–7 d, 0.2 mg/kg followed by 2 doses of 0.2 mg/kg q12–24h; <7 d, 0.2 mg/kg followed by 2 doses of 0.25 mg/kg q12–24h

Administration

Oral

• Give immediately after meals, or with food, milk, or antacid (if prescribed) to minimize GI side effects.

Rectal

• Indomethacin rectal suppository use is contraindicated with history of proctitis or recent bleeding.

Intravenous PREPARE: Direct: Dilute 1 mg with 1 mL of NS or sterile water for injection without preservatives. Resulting concentration (1 mg/mL) may be further diluted with an additional 1 mL for each 1 mg to yield 0.5 mg/mL.   ADMINISTER: Direct: Give by direct IV with a single dose given over 20–30 min.   INCOMPATIBILITIES Y-site: Amino acid, calcium gluconate, cimetidine, dobutamine, dopamine, gentamicin, levofloxacin, tobramycin, tolazoline. Avoid extravasation or leakage; drug can be irritating to tissue. Discard any unused drug, since it contains no preservative.

• Store oral and rectal forms in tight, light-resistant containers unless otherwise directed. Do not freeze.

Adverse Effects (≥1%)

Body as a Whole: Hypersensitivity (rash, purpura, pruritus, urticaria, angioedema, angiitis, rapid fall in blood pressure, dyspnea, asthma syndrome in aspirin-sensitive patients), edema, weight gain, flushing, sweating. CNS: Headache, dizziness, vertigo, light-headedness, syncope, fatigue, muscle weakness, ataxia, insomnia, nightmares, drowsiness, confusion, coma, convulsions, peripheral neuropathy, psychic disturbances (hallucinations, depersonalization, depression), aggravation of epilepsy, parkinsonism. CV: Elevated BP, palpitation, chest pains, tachycardia, bradycardia, CHF. Special Senses: Blurred vision, lacrimation, eye pain, visual field changes, corneal deposits, retinal disturbances including macula, tinnitus, hearing disturbances, epistaxis. GI: Nausea, vomiting, diarrhea, anorexia, bloating, abdominal distention, ulcerative stomatitis, proctitis, rectal bleeding, GI ulceration, hemorrhage, perforation, toxic hepatitis. Hematologic: Hemolytic anemia, aplastic anemia (sometimes fatal), agranulocytosis, leukopenia, thrombocytopenic purpura, inhibited platelet aggregation. Urogenital: Renal function impairment, hematuria, urinary frequency; vaginal bleeding, breast changes. Skin: Hair loss, exfoliative dermatitis, erythema nodosum, tissue irritation with extravasation. Metabolic: Hyponatremia, hypokalemia, hyperkalemia, hypoglycemia or hyperglycemia, glycosuria (rare).

Diagnostic Test Interference

Increased AST, ALT, bilirubin, BUN; positive direct Coombs' test.

Interactions

Drug: oral anticoagulants, heparin, alcohol may prolong bleeding time; may increase lithium toxicity; effects of oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas increased because of protein-binding displacement; increased toxicity including GI bleeding with salicylates, nsaids; may blunt effects of antihypertensives and diuretics. Herbal: Feverfew, garlic, ginger, ginkgo may increase bleeding potential.

Pharmacokinetics

Absorption: Completely absorbed from GI tract. Onset: 1–2 h. Peak: 3 h. Duration: 4–6 h. Metabolism: In liver. Elimination: Primarily in urine. Half-Life: 2.5–124 h.

Nursing Implications

Assessment & Drug Effects

• Monitor for therapeutic effectiveness: In acute gouty attack, relief of joint tenderness and pain is usually apparent in 24–36 h; swelling generally disappears in 3–5 d. In rheumatoid arthritis: Reduced fever, increased strength, reduced stiffness, and relief of pain, swelling, and tenderness.
• Question patient carefully regarding aspirin sensitivity before initiation of therapy.
• Observe patients carefully; instruct to report adverse reactions promptly to prevent serious and sometimes irreversible or fatal effects.
• Lab tests: Monitor renal function, hepatic function, CBC with differential, BP and HR, visual and hearing acuity periodically.
• Monitor weight and observe dependent areas for signs of edema in patients with underlying cardiovascular disease.
• Monitor I&O closely and keep physician informed during IV administration for patent ductus arteriosus. Significant impairment of renal function is possible; urine output may decrease by 50% or more. Also monitor BUN, serum creatinine, glomerular filtration rate, creatinine clearance, and serum electrolytes.

Patient & Family Education

• Notify physician of S&S of GI bleeding, visual disturbance, tinnitus, weight gain, or edema.
• Do not take aspirin or other NSAIDs; they increase possibility of ulcers.
• Note: Frontal headache is the most frequent CNS adverse effect; if it persists, dosage reduction or drug withdrawal may be indicated. Take drug at bedtime with milk to reduce the incidence of morning headache.
• Do not drive or engage in other potentially hazardous activities until response to drug is known.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug