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NSAID — COX Inhibitor (PDA Closure in Neonates) Pregnancy: Contraindicated in late pregnancy (causes premature closure of ductus arteriosus in utero). Neonatal use only.

Indomethacin (Patent Ductus Arteriosus)

Brand names: Indocid IV

Adult dose

Dose: Not applicable for PDA indication — neonatal use only
Route: N/A
Frequency: N/A
Max: N/A
PDA closure is a neonatal indication. For adult arthritis indications — see general medicine file.

Paediatric dose

Dose: IV: 3 doses of 0.1–0.25 mg/kg IV every 12–24 hours. Dose by postnatal age: <48h old: 0.1 mg/kg per dose; 2–7 days: 0.2 mg/kg per dose; >7 days: 0.25 mg/kg per dose mg/kg
Route: Intravenous (slow infusion over 20–30 min)
Frequency: Every 12–24 hours for 3 doses
Max: 0.25 mg/kg per dose
Patent ductus arteriosus in premature neonates. Older postnatal age = higher dose (COX-2 expression increases with age). Doses given 12–24h apart × 3 doses. If not closed after 1 course — may repeat (specialist decision). Alternative: ibuprofen IV (equal efficacy, less renal impairment). Note: ibuprofen generally preferred in UK neonatal units due to less renal/cerebral blood flow reduction. Source: BNF for Children 2024.

Dose adjustments

Renal

Serum creatinine >130 micromol/L or urine output <0.6 mL/kg/h: withhold until renal function improves. Indomethacin significantly reduces renal blood flow — major neonatal concern.

Hepatic

Use with caution in hepatic impairment.

Paediatric weight-based calculator

Patent ductus arteriosus in premature neonates. Older postnatal age = higher dose (COX-2 expression increases with age). Doses given 12–24h apart × 3 doses. If not closed after 1 course — may repeat (specialist decision). Alternative: ibuprofen IV (equal efficacy, less renal impairment). Note: ibuprofen generally preferred in UK neonatal units due to less renal/cerebral blood flow reduction. Source: BNF for Children 2024.

Clinical pearls

  • PDA significance: in premature infants, the ductus arteriosus often fails to close spontaneously, allowing left-to-right shunting → pulmonary overcirculation + systemic underperfusion → respiratory failure, renal failure, NEC. Pharmacological closure reduces need for surgical ligation.
  • Prostaglandin E2 keeps PDA open: the ductus arteriosus remains patent through fetal/early neonatal life via PGE2 stimulation of smooth muscle relaxation. Indomethacin (COX-1/2 inhibitor) reduces PGE2 synthesis → ductal smooth muscle constriction → PDA closure. Works best in extremely preterm neonates (higher PGE2 dependency).
  • Ibuprofen IV vs indomethacin: equally effective for PDA closure (Cochrane review). Ibuprofen has less renal blood flow reduction (less COX-1 inhibition at renal vasculature) — preferred in most UK neonatal units. Indomethacin may have neuroprotective benefit (reduces IVH incidence) — historical use as prophylactic in ELBW infants, though routine prophylaxis is debated.
  • Monitoring urine output is critical: oliguria (urine output <0.5 mL/kg/h) is the most common adverse effect. Restrict fluid intake during treatment to maintain positive balance without overloading. Withhold indomethacin if creatinine >130 micromol/L or UO drops <0.6 mL/kg/h — resume when renal function recovers.
  • NEC precaution: avoid feeding or ensure feeds are minimal during indomethacin course. Gut mucosal prostaglandins (PGI2, PGE2) protect intestinal integrity. COX inhibition impairs this protection — hold or reduce enteral feeds and monitor abdomen carefully during the 3-dose course. Source: BNF for Children 2024; Ohlsson et al. Cochrane 2020 (indomethacin PDA).

Contraindications

  • Active bleeding or significant bleeding tendency (especially IVH — intraventricular haemorrhage of grade 3–4)
  • Thrombocytopenia <50 × 10⁹/L
  • Coagulation defects
  • Necrotising enterocolitis (NEC) or bowel perforation — prostaglandin inhibition impairs gut mucosal integrity
  • Renal impairment (creatinine >130 micromol/L) or oliguria
  • Untreated sepsis

Side effects

  • Renal impairment (reduced urine output — most common; monitor urine output hourly during treatment)
  • Reduced intestinal blood flow (NEC risk — monitor for abdominal distension, bloody stools)
  • Reduced cerebral blood flow (theoretical concern — may contribute to periventricular leukomalacia risk, though prophylactic use shows neuroprotection)
  • Hyponatraemia (water retention via renal prostaglandin inhibition)
  • Reduced platelet aggregation (bleeding risk)
  • Reduced pulmonary vascular resistance (beneficial in PPHN context)

Interactions

  • Aminoglycosides (gentamicin): indomethacin reduces renal clearance → increased gentamicin levels — extend gentamicin interval and monitor levels closely
  • Digoxin: indomethacin increases digoxin concentrations — monitor digoxin levels
  • Furosemide: prostaglandin inhibition may blunt furosemide diuretic effect; some centres add furosemide to counteract indomethacin-induced oliguria
  • Anticoagulants: avoid concurrent use (platelet inhibition)

Monitoring

  • Urine output hourly (target ≥0.5–1 mL/kg/h during treatment — withhold if oliguria)
  • Serum creatinine and electrolytes (Na+, K+) before each dose
  • Echocardiogram (at baseline and after course to confirm PDA closure)
  • Abdominal examination (NEC surveillance — distension, bilious aspirates, bloody stools)
  • Platelet count before each dose (withhold if <50 × 10⁹/L)
  • Head ultrasound (IVH monitoring in ELBW neonates)

Reference: BNF for Children 2024; Ohlsson et al. Cochrane 2020; British Association of Perinatal Medicine (BAPM) PDA guidelines. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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