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 |
| Molecular Weight | 433.88 Da (as indomethacin sodium trihydrate; indomethacin free acid MW = 357.79 Da) |
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 | Avoid use during first trimester unless absolutely necessary. Associated with increased risk of spontaneous abortion and congenital malformations, particularly cardiac defects. |
| 2nd trimester | Avoid use during second trimester due to potential oligohydramnios and fetal renal impairment. Non-teratogenic but may cause premature ductus arteriosus constriction and oligohydramnios. |
| 3rd trimester | Contraindicated in third trimester due to risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal complications including persistent pulmonary hypertension and renal impairment. |
Clinical note
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious cardiovascular thrombotic events and GI bleeding.
| FDA category | Positive |
| Placental transfer | Indomethacin readily crosses the placenta with fetal plasma concentrations approximately 50% of maternal levels. Complete placental transfer occurs, with detectable levels in fetal tissues. |
■ 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 |
History of aspirin or NSAID-induced asthmaActive peptic ulcer disease or gastrointestinal bleedingSevere renal impairment (CrCl <30 mL/min)Third trimester of pregnancyKnown hypersensitivity to indomethacin or any component of the formulationHistory of proctitis or recent rectal bleeding (for suppository form)
| 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). |
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| Breastfeeding | Indomethacin is excreted into breast milk in low concentrations (milk-to-plasma ratio ~0.1-0.2). Theoretical risk of adverse effects in nursing infants, particularly with prolonged use or high doses. Monitor infant for signs of gastrointestinal bleeding, renal impairment, or platelet dysfunction. Generally compatible with breastfeeding with caution, especially with short-term use. |
| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | 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. |
| Food/Dietary | Avoid alcohol as it increases risk of GI bleeding and ulceration. No specific food interactions, but taking with food or milk can reduce GI irritation. Maintain adequate hydration to prevent renal toxicity, but avoid excessive salt intake if fluid retention is a concern. |
| Clinical Pearls | Indomethacin sodium is highly effective for acute gout but carries significant GI and renal risks. Use lowest effective dose for shortest duration. Monitor renal function and electrolytes, especially in elderly or dehydrated patients. Can cause headache, dizziness, and confusion; caution in patients with history of seizures or psychiatric disorders. Avoid concurrent use with other NSAIDs, anticoagulants, and lithium. In neonates, indomethacin is used to close patent ductus arteriosus, but monitor for oliguria and platelet dysfunction. |
| Patient Advice | Take with food or milk to reduce stomach upset. · Avoid alcohol while taking this medication. · Do not take aspirin or other NSAIDs (e.g., ibuprofen, naproxen) without consulting your doctor. · Report any signs of stomach bleeding (black/tarry stools, vomiting blood) or kidney problems (decreased urination, swelling) immediately. · May cause dizziness or drowsiness; avoid driving or operating machinery until you know how it affects you. · Take exactly as prescribed; do not increase dose or frequency without your doctor's approval. · Store at room temperature away from moisture and heat. |