INDOCIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INDOCIN (INDOCIN).
Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, thereby reducing prostaglandin synthesis, which mediates inflammation, pain, and fever. It also decreases renal blood flow and may cause ductus arteriosus closure.
| Metabolism | Primarily hepatic metabolism via O-demethylation and N-deacylation; minor pathways include glucuronidation. Involved enzymes include CYP2C9 and possibly CYP3A4. |
| Excretion | Renal (60% as unchanged drug and glucuronide conjugates), biliary/fecal (33% via enterohepatic circulation). |
| Half-life | Terminal elimination half-life approximately 4.5 hours (range 2.6–11.2 hours); prolonged in elderly and patients with hepatic impairment. |
| Protein binding | Approximately 90% bound to albumin (saturable binding at high concentrations). |
| Volume of Distribution | 0.1–0.2 L/kg (indicating low tissue penetration; primarily in plasma and interstitial fluid). |
| Bioavailability | Oral: 100% (immediate release); Rectal: 80–90%; IV: 100%. |
| Onset of Action | Oral: 0.5–1 hour for analgesic effect; Rectal: 0.5–1 hour; IV: Immediate (within minutes). |
| Duration of Action | Oral/analgesic: 4–6 hours; Anti-inflammatory: up to 12 hours with sustained release. Note: Duration correlates with synovial fluid levels. |
| Action Class | Quinolones/ Fluroquinolones |
| Brand Substitutes | Oflotas 200mg Tablet, Olox 200mg Tablet, Oflamed 200 Tablet, Oxa 200mg Tablet, Zenflox 200 Tablet |
25 mg orally 2-3 times daily; maximum 200 mg/day. Intravenous: 0.5-1 mg/kg as single dose for ductus arteriosus closure.
| Dosage form | SUSPENSION |
| Renal impairment | CrCl 10-50 mL/min: dose reduction 50%; CrCl <10 mL/min: avoid use or reduce to 25% of usual dose. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | For inflammatory conditions: 1-2 mg/kg/day in 3-4 divided doses; maximum 4 mg/kg/day or 200 mg/day. For patent ductus arteriosus: IV 0.2-0.25 mg/kg/dose every 12-24 hours for 3 doses. |
| Geriatric use | Initiate at 25 mg twice daily; maximum 100 mg/day; monitor renal function and GI bleeding risk. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INDOCIN (INDOCIN).
| Breastfeeding | Indomethacin is excreted into breast milk in low concentrations (M/P ratio approximately 0.1-0.4). Use with caution, especially in infants with known cardiovascular or renal compromise. Consider alternatives if possible. |
| Teratogenic Risk | First trimester: Avoid because of risk of spontaneous abortion and congenital malformations (cardiac, orofacial clefts) based on epidemiologic studies. Second/third trimester: Contraindicated due to risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal renal impairment. |
■ FDA Black Box Warning
Cardiovascular Risk: NSAIDs increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk increases with duration of use and in patients with cardiovascular disease or risk factors. Indomethacin is contraindicated for treatment of perioperative pain in coronary artery bypass graft (CABG) surgery. Gastrointestinal Risk: NSAIDs increase the risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time without warning symptoms, and elderly patients and those with prior history of peptic ulcer disease or GI bleeding are at greater risk.
| Serious Effects |
History of allergic reaction to indomethacin or aspirin; history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs; perioperative pain in CABG surgery; severe renal impairment; active GI bleeding or peptic ulcer disease.
| Precautions | Cardiovascular thrombotic events; GI bleeding, ulceration, and perforation; renal toxicity including renal papillary necrosis; anemia; hepatic effects; hypertension; exacerbation of asthma; fluid retention; skin reactions including Stevens-Johnson syndrome; central nervous system effects including dizziness and headache; use in pregnancy (avoid in third trimester). |
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| Fetal Monitoring |
| Monitor maternal renal function, blood pressure, and signs of gastrointestinal bleeding. Perform fetal ultrasound to assess amniotic fluid volume and ductus arteriosus if used in pregnancy. |
| Fertility Effects | May impair female fertility by interfering with ovulation (reversible upon discontinuation). No known effect on male fertility. |
| Food/Dietary | Avoid alcohol, as it increases the risk of gastrointestinal bleeding and liver toxicity. Take with food or milk to minimize gastrointestinal irritation. Limit salt intake to reduce fluid retention and hypertension risk. Avoid high-potassium foods if renal impairment is present, as indomethacin can increase potassium levels. |
| Clinical Pearls | Indomethacin (Indocin) is a potent NSAID with significant anti-inflammatory, analgesic, and antipyretic effects. It is particularly effective for acute gout flares and closure of patent ductus arteriosus (PDA) in neonates. Due to high risk of gastrointestinal bleeding, renal impairment, and cardiovascular events, use the lowest effective dose for the shortest duration. Contraindicated in patients with history of aspirin or NSAID-induced asthma, urticaria, or allergic reactions. Monitor renal function, blood pressure, and signs of GI bleeding. Avoid concurrent use with other NSAIDs, anticoagulants, and corticosteroids. |
| Patient Advice | Take with food, milk, or an antacid to reduce stomach upset. · Report any black/bloody stools, coffee-ground vomit, chest pain, shortness of breath, or signs of bleeding immediately. · Avoid alcohol, aspirin, and other NSAIDs (e.g., ibuprofen, naproxen) while taking this medication. · Do not take if you are allergic to aspirin or any NSAID, or if you have a history of asthma attacks after taking these drugs. · Notify your healthcare provider if you have kidney disease, high blood pressure, heart disease, or are pregnant or breastfeeding. |