Treatment of Patent Ductus Arteriosus: Indomethacin or Ibuprofen?

Abstract

We compared ibuprofen and indomethacin for the treatment of patent ductus arteriosus (PDA) in preterm infants. A retrospective comparative study was conducted at a pediatric tertiary center in preterm infants diagnosed with PDA. Infants born from January 2000 to June 2003 were treated with indomethacin, whereas infants born from July 2003 to November 2005 were treated with ibuprofen. The two treatment groups were compared. Demographic data and clinical, laboratory, and outcome data were collected from the medical files. Seventy-three infants were included in the ibuprofen group and 46 in the indomethacin group. No significant difference in efficacy was found between indomethacin and ibuprofen. Compared with ibuprofen, indomethacin treatment was associated with significantly higher mean creatinine levels and a higher percent of infants with creatinine >1.2 mg/dL, hyponatremia <120 mmol/L, and platelet level <100,000 platelets/mL(3). There were no significant differences in bilirubin levels, incidence and grade of intraventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, rate of surgical duct ligation, sepsis, length of hospital stay, or mortality. Indomethacin and ibuprofen are equally effective for PDA closure in premature infants. Treatment with ibuprofen is safer, decreasing the risk of renal failure, thrombocytopenia, and hyponatremia.

Patent Ductus Arteriosus in Premature Neonates

“…Both intravenous indomethacin (RR 2.39, 95% CI 2.05 to 2.78) and intravenous ibuprofen (RR 2.40, 95% CI 2.03 to 2.84) closed a PDA more effectively than placebo. Other studies [98, 99] have shown a similar efficacy of the two drugs. The two drugs also have a similar failure rate for PDA closure, ranging between 0-50%; Ohlsson et al [100] performed a meta-analysis on data from 19 trials (n=956 infants) for failure rates after 1-3 doses of ibuprofen compared to indomethacin.…”

Differential renal adverse effects of ibuprofen and indomethacin in preterm infants: a review

“…Before treatment, creatinine serum concentrations were 0.93±0.20 mg/dL (ibuprofen) and 0.96±0.21 mg/dL (indomethacin) (were not significantly different); after treatment, the serum creatinine concentrations were 0.98±0.24 mg/dL (ibuprofen; P <0.005) and 1.06±0.24 mg/dL (indomethacin; P <0.005) 15. The ibuprofen serum concentration was 1.05±0.36 mg/dL and the serum indomethacin concentration was 1.33±0.46 mg/dL ( P <0.001) 24 hours after administration 22. During the period 2–7 days after treatment, the ibuprofen serum creatinine concentration was 1.11±0.39 mg/dL and the indomethacin serum creatinine concentration was 1.53±0.5 mg/dL ( P <0.001) 22.…”

“…The pharmacological basis for the medical treatment of PDA was found, and consists of the inhibition of prostaglandin E 2 by cyclooxygenase inhibitors 8–22. Indomethacin was the first cyclooxygenase inhibitor to enter clinical use for the therapeutic treatment of PDA; it has been used for many years, and is still used today.…”

“…In the literature, there are several articles10,15,19,21,22,24,26 that compare the nephrotoxicity following the administration of ibuprofen or indomethacin to neonates; however, there are no reviews that summarize the effects of ibuprofen or indomethacin on the urine output, the serum creatinine clearance, and oliguria reported by various studies. Thus, this review supplies useful information for neonatologists.…”

Ibuprofen and indomethacin for the closure of the patent ductus arteriosus

“…Treatment with ibuprofen is safer, decreasing the risk of renal failure, and hyponatremia. 26 There are conflicting results about the ductal closure rate by oral indomethacin and oral ibuprofen. Fakhrae et al 27 found that the patent ductus arteriosus is closed in all preterm infants (100%) treated with oral ibuprofen and Ibuprofen and indomethacin in neonates Pacifici GM recém-nascidos maduros, o canal arterial se fecha após o nascimento.…”