INDOMETHACIN
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Non-selective cyclooxygenase (COX-1 and COX-2) inhibitor, reducing prostaglandin synthesis.
| Metabolism | Primarily hepatic via O-demethylation, N-deacylation, and glucuronidation. Enzymes: CYP2C9 (minor), UGTs. |
| Excretion | Renal excretion of unchanged drug and metabolites (approximately 60% as parent drug and glucuronide conjugate; 23% as O-desmethyl metabolite; 13% as glucuronide of O-desmethyl metabolite); biliary/fecal elimination accounts for 30-40%, primarily as glucuronide conjugates. |
| Half-life | Terminal elimination half-life is approximately 4.5 hours (range 2.6-11.2 hours) in adults; prolonged in neonates (up to 17 hours) and in patients with renal impairment or cholestasis; clinical context: dosing interval adjustments needed in hepatic or renal disease. |
| Protein binding | 99% bound, primarily to albumin. |
| Volume of Distribution | 0.34-1.57 L/kg; large Vd indicates extensive tissue distribution; crosses blood-brain barrier and placenta. |
| Bioavailability | Oral: near 100% (almost complete absorption); Rectal: approximately 80% of oral; IV: 100%. |
| Onset of Action | Oral: 30 minutes (antipyretic, analgesic); Rectal: 30-60 minutes; Intravenous: rapid, within minutes for closure of ductus arteriosus. |
| Duration of Action | Oral: 4-6 hours (analgesic, antipyretic); Rectal: 4-6 hours; IV: effects on ductus closure persist for 24-48 hours after infusion; clinical note: anti-inflammatory effect may require 1-2 weeks of continuous therapy. |
| Molecular Weight | 357.79 |
| Action Class | NSAID's- Non-Selective COX 1&2 Inhibitors (acetic acid) |
25-50 mg orally 2-3 times daily; maximum 200 mg/day. Also available as 75 mg sustained-release capsule orally once daily, or 50 mg rectally 3-4 times daily.
| Dosage form | CAPSULE |
| Renal impairment | GFR 10-50 mL/min: reduce dose by 25%; GFR <10 mL/min: avoid use or reduce dose by 50%. |
| Liver impairment | Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use. |
| Pediatric use | For patent ductus arteriosus: 0.2 mg/kg IV initially, then 0.1 mg/kg at 12-24 hour intervals, up to 3 doses. For other indications: 1-2 mg/kg/day orally in 2-4 divided doses, maximum 4 mg/kg/day. |
| Geriatric use | Initiate at lowest effective dose (e.g., 25 mg twice daily) due to increased risk of GI, renal, and CNS adverse effects. Monitor renal function and adjust accordingly. |
| 1st trimester | Associated with increased risk of miscarriage and congenital malformations (e.g., cardiovascular). Avoid use unless absolutely necessary. |
| 2nd trimester | May cause oligohydramnios and fetal renal impairment. Use only if potential benefit justifies risk to fetus. |
| 3rd trimester | Contraindicated due to risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal complications (e.g., persistent pulmonary hypertension). Avoid after 30 weeks. |
Clinical note
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious cardiovascular thrombotic events and GI bleeding.
| Placental transfer | Crosses placenta; fetal serum concentrations can reach 50% of maternal levels. Demonstrated in human studies. |
| Breastfeeding | Excreted into breast milk in low amounts; however, due to potential for adverse effects in the infant (e.g., seizures, apnea), especially in neonates, use with caution and monitor infant. American Academy of Pediatrics considers compatible with breastfeeding. |
â– FDA Black Box Warning
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Risk may be increased in patients with existing cardiovascular disease or risk factors. Indomethacin is contraindicated for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Serious Effects |
Hypersensitivity to indomethacin or NSAIDsHistory of asthma, urticaria, or allergic reactions after aspirin or other NSAIDsActive peptic ulcer disease or gastrointestinal bleedingAdvanced renal diseasePerioperative pain in setting of coronary artery bypass graft (CABG) surgeryThird trimester of pregnancyNeonates with certain conditions (e.g., necrotizing enterocolitis, thrombocytopenia)
| Precautions | Cardiovascular risk (thrombotic events, hypertension, fluid retention); Gastrointestinal risk (ulceration, bleeding, perforation); Renal risk (acute renal injury, nephrotoxicity); Hematologic (inhibition of platelet aggregation, prolonged bleeding time); Central nervous system (CNS) effects (headache, dizziness, depression, psychosis); Hepatic toxicity; Use in pregnancy (third trimester may cause premature closure of ductus arteriosus). |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Risk of cardiac defects (odds ratio 1.86) and oral clefts; second/third trimester: Premature closure of ductus arteriosus, oligohydramnios, necrotizing enterocolitis, intracranial hemorrhage; avoid after 30 weeks gestation. |
| Fetal Monitoring | Fetal echocardiography for ductal patency and amniotic fluid index via ultrasound; maternal renal function, platelet count, and blood pressure monitoring; avoid if significant oligohydramnios or ductal constriction. |
| Fertility Effects | Reversible inhibition of ovulation due to prostaglandin synthesis inhibition; may delay conception; no evidence of permanent infertility. |
| Food/Dietary |
| Avoid alcohol; may increase gastrointestinal irritation and bleeding risk. No specific food restrictions, but take with food to minimize GI upset. Avoid high-sodium foods if fluid retention is a concern. |
| Clinical Pearls | Indomethacin is a potent NSAID with high CNS penetration; use with caution in elderly due to risk of confusion and dizziness. It is a first-line agent for closure of patent ductus arteriosus in neonates. Be aware of increased risk of gastrointestinal bleeding, renal impairment, and cardiovascular events. Monitor renal function and electrolytes, especially in patients with heart failure or on diuretics. Avoid in patients with aspirin-induced asthma. |
| Patient Advice | Take with food or milk to reduce stomach upset. · Do not drink alcohol while taking this medication; it increases risk of stomach bleeding. · Report any signs of bleeding (black/tarry stools, vomit that looks like coffee grounds) or chest pain. · Avoid taking with other NSAIDs (like ibuprofen) or aspirin unless directed by a doctor. · Contact your doctor if you experience weight gain, swelling, or shortness of breath. · Use for shortest duration necessary to control symptoms. |