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indomethacin (Indocin)

Tradename: Indocin. Indications: - temporary relief of minor pains, fevers & inflammation - bursitis - treatment of acute flairs of gout - treatment of pericarditis - alternative to surgery for closure of patent ductus arteriosus in neonates - Bartter syndrome [5] - nephrogenic diabetes insipidus - premature labor [5] Contraindications: 1) other NSAIDs 2) active GI bleeding 3) peptic ulcer disease 4) impaired renal function 5) platelet count < 60,000/mm3 6) may excerbate asthma [6] Dosage: 25-50 mg TID, max 200 mg/day Tabs: 25 & 50 mg tabs Suppository: 50 mg Suspension: 25 mg/5 mL. Indocin SR: 75 mg PO BID/QD. 75 mg. Pharmacokinetics: 1) rapid absorption from the GI tract 2) onset of action: within 30 minutes to several hours 3) extensive enterohepatic recirculation 4) duration of action 4-12 hours 5) 1/2life is 2.4 hours Adverse effects: 1) common (> 10%) a) skin rash b) dizziness c) abdominal cramps d) heartburn e) indigestion f) nausea 2) less common (1-10%) - itching, tinnitus, fluid retention, headache, nervousness, vomiting 3) uncommon (< 10%) - congestive heart failure, hypertension, arrhythmias,epistaxis, confusion, hallucinations, aseptic meningitis, mental depression, peripheral neuropathy, hives, erythema multiforme, epidermal necrolysis, Stevens-Johnson syndrome, gastritis, GI ulceration, cystitis, agranulocytosis, anemia, bone marrow suppression, leukopenia, thrombocytopenia, hepatitis, angioedema, allergic rhinitis, toxic amblyopia, blurred vision, conjunctivitis, dry eyes, hearing loss, polyuria, shortness of breath, polydipsia, tachycardia, hot flashes, drowsiness, insomnia, acute renal failure Drug interactions: 1) corticosteroids a) increase the clearance of salicylates b) increased renal toxicity when used in combination 2) decreased antihypertensive effect of ACE inhibitor 3) increased anticoagulant effect of warfarin 4) aluminum & magnesium hydroxide may decrease rate but not extent of indomethacin absorption 5) bicarbonate increases rate of indomethacin absorption 6) probenecid increases indomethacin concentrations 7) indomethacin may decrease renal elimination of: a) Li+ b) digoxin c) methotrexate 8) indomethacin may inhibit diuretic effect of furosemide Laboratory: 1) specimen: a) serum, plasma (EDTA), urine, gastric fluid b) stable for at least 14 days at -20 degrees C 2) methods: a) serum/plasma: HPLC, GC, GC-MS, TLC, RIA, EIA b) urine: GC, HPLC, TLC, RIA 3) labs with Loincs - indomethacin in specimen - indomethacin in gastric fluid - indomethacin in serum/plasma - indomethacin in urine Mechanism of action: 1) acetic acid class NSAID 2) analgesic 3) antipyretic 4) anti-inflammatory agent

Interactions

drug interactions drug adverse effects of NSAIDs monitor with non steroidal anti-inflammatory agents (NSIADs)

General

indole non-steroidal anti-inflammatory agent (NSAID) peroxisome proliferator; PPAR agonist; PPAR gamma agonist

Properties

INHIBITS: cyclooxygenase MISC-INFO: elimination route LIVER 1/2life 1-16 HOURS therapeutic-range 0.5-3.0 UG/ML protein-binding >90% elimination by hemodialysis - peritoneal dialysis - pregnancy-category ? safety in lactation -

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
  5. Deprecated Reference
  6. NEJM Knowledge+ Allergy/Immunology