INDOMETHACIN SODIUM
Clinical safety rating: avoid
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious cardiovascular thrombotic events and GI bleeding.
Non-selective inhibition of cyclooxygenase (COX-1 and COX-2), reducing prostaglandin synthesis, leading to anti-inflammatory, antipyretic, and analgesic effects.
| Metabolism | Hepatic metabolism via O-demethylation, N-deacylation, and glucuronidation; minor oxidation. CYP450 involvement is limited; primarily via UGT (glucuronidation). |
| Excretion | Renal (60% as unchanged drug and metabolites, predominantly glucuronide conjugate); fecal (33%, primarily via biliary secretion); <5% unchanged in urine |
| Half-life | Terminal elimination half-life: 4.5 hours (range 2.6–11.2 hours); half-life may be prolonged in neonates, elderly, and renal impairment |
| Protein binding | 99% bound to albumin |
| Volume of Distribution | 0.34–0.72 L/kg (suggesting extensive tissue distribution, particularly to inflamed sites) |
| Bioavailability | Oral: 98% (immediate-release); 80–90% (sustained-release). Ophthalmic: negligible systemic absorption |
| Onset of Action | Oral: 30 minutes (antipyretic/analgesic); 2 hours (anti-inflammatory). Intravenous: rapid (minutes) for antipyresis. Ophthalmic: 1 hour for intraocular inflammation control |
| Duration of Action | Oral: 4–6 hours (analgesic/antipyretic); anti-inflammatory effect persists for up to 1 week with continued dosing. Intravenous: dose-dependent, typically 4–6 hours |
Intravenous: 0.5 mg/kg every 12 hours or 0.25 mg/kg every 6 hours for patent ductus arteriosus closure in neonates. Oral/immediate-release: 25-50 mg two to three times daily. Extended-release: 75 mg once daily or 75 mg twice daily. Maximum daily dose: 200 mg.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 30-60 mL/min: No adjustment needed. GFR 15-29 mL/min: Consider dose reduction by 25-50% or extended dosing interval. GFR <15 mL/min: Avoid use or use with extreme caution; maximum dose 100 mg/day if necessary. |
| Liver impairment | Child-Pugh A: No dose adjustment. Child-Pugh B: Reduce initial dose by 50% and titrate cautiously; monitor for toxicity. Child-Pugh C: Contraindicated or avoid use due to risk of hepatic encephalopathy and bleeding. |
| Pediatric use | Intravenous for patent ductus arteriosus: 0.2 mg/kg initially, then 0.1 mg/kg at 12-hour intervals for 3 doses. Oral for juvenile rheumatic conditions: 1.5-3 mg/kg/day in divided doses every 8-12 hours. Maximum daily dose: 4 mg/kg/day (not to exceed 200 mg). |
| Geriatric use | Initiate at lowest effective dose, starting with 25 mg twice daily oral or IV 0.25-0.5 mg/kg once daily. Titrate slowly. Reduce total daily dose by 50% compared to younger adults. Risk of GI bleeding and renal impairment; monitor closely. Maximum daily dose: 100-150 mg. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious cardiovascular thrombotic events and GI bleeding.
| FDA category | Positive |
| Breastfeeding | Indomethacin is excreted into breast milk in low amounts (M/P ratio approximately 0.5-1.0). Relative infant dose is estimated at 1-2% of maternal weight-adjusted dose. Cases of neonatal seizures reported with maternal use. Caution is advised; alternative agents preferred if possible, especially in neonates with thrombocytopenia or renal impairment. |
| Teratogenic Risk |
■ FDA Black Box Warning
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors may be at greater risk. Indomethacin is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Common Effects | pain |
| Serious Effects |
Hypersensitivity to indomethacin or any NSAID, history of asthma, urticaria, or allergic-type reactions after taking aspirin or NSAIDs, active or recent gastrointestinal bleeding or perforation, perioperative pain in setting of CABG surgery, advanced renal disease, lactation (use with caution), pregnancy (especially third trimester).
| Precautions | Cardiovascular risk (thrombotic events, hypertension), gastrointestinal risk (bleeding, ulceration, perforation), renal toxicity (impaired renal function, nephrotoxicity), hepatic effects (elevated liver enzymes, hepatic failure), hematologic effects (anemia, platelet inhibition), anaphylactoid reactions, exacerbation of asthma, CNS effects (dizziness, headache, depression), ocular effects (corneal deposits, retinal toxicity), premature closure of ductus arteriosus in utero, use in pregnancy (avoid during third trimester due to premature closure). |
Loading safety data…
| FDA Pregnancy Category C (first and second trimester) and Category D (third trimester). Indomethacin crosses the placenta. First trimester: Possible increased risk of cardiac defects (case-control studies show OR 1.5-2.0 for cardiovascular malformations). Second trimester: Avoid prolonged use due to risk of oligohydramnios. Third trimester: Contraindicated after 30-32 weeks gestation due to risk of premature closure of the ductus arteriosus (increases with gestational age), oligohydramnios, and neonatal complications (pulmonary hypertension, renal dysfunction). |
| Fetal Monitoring | Monitor maternal renal function, blood pressure, and signs of bleeding. Fetal monitoring includes serial ultrasound for amniotic fluid index (oligohydramnios risk) and ductus arteriosus patency (Doppler echocardiography) in third trimester. Neonatal monitoring: assess for bleeding, renal function, and pulmonary hypertension following in utero exposure. |
| Fertility Effects | Indomethacin may impair fertility in females by inhibiting ovulation (prostaglandin-dependent). Reversible upon discontinuation. In males, no well-documented fertility impairment. |