2.14 Drugs affecting the ductus arteriosus

(a) closure of the ductus arteriosus

First Choice:
indometacin
Second Choice:
ibuprofen
Dose
  • indometacin injection 1mg (as sodium trihydrate): by intravenous injection, over 20–30 minutes (using a suitable syringe driver), 3 doses at intervals of 12–24 hours (provided urine output remains adequate)
    • Age less than 48 hours, 200micrograms/kg then 100micrograms/kg then 100micrograms/kg.
    • Age 2–7 days, 200micrograms/kg then 200micrograms/kg then 200micrograms/kg.
    • Age over 7 days, 200micrograms/kg then 250micrograms/kg then 250micrograms/kg.
    If ductus arteriosus re-opens a second course of 3 injections may be given 48 hours after first course.
  • ibuprofen injection 5mg/ml
    • All ages, by slow intravenous injection, initially 10mg/kg as a single dose followed at 24-hour intervals by 2 doses of 5mg/kg; course may be repeated after 48 hours if necessary.
Prescribing Notes
  • Subsequent doses should be delayed if urine output is less than 0.6ml/kg/hr.
  • If two course of indomethacin hasn't worked an alternative regimen of 100micrograms/kg/day for 6 days may be used.
(b) maintenance of patency

First Choice:
dinoprostone
Dose
  • dinoprostone (prostaglandin E2) intravenous solution, for dilution (diluted to 1microgram/ml), and use as an infusion, dinoprostone 1mg/mL. By continuous intravenous infusion
    • Neonate initially 5-10 nanograms/kg/minute, increased as necessary in 5 nanograms/kg/minute increments up to 20 nanogram/kg/minute
Prescribing Notes
  • Dinoprostone is a potent vasodilator, effective in maintaining the patency of the ductus arteriosus whilst awaiting surgery.
  • During infusion monitor heart rate, blood pressure, respiratory rate and core body temperature.
  • The incidence of adverse effects is dose related. Respiratory depression or apnoea are common in infants less than 2kg. CNS effects such as seizures, pyrexia, irritability and lethargy can occur. Hypotension, nausea, vomiting and diarrhoea are expected common side effects. Rash is a commonly reported side effect in neonates.