Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2015 Dec;91(12):725-9.
doi: 10.1016/j.earlhumdev.2015.08.003. Epub 2015 Sep 19.

Comparative effectiveness and safety of indomethacin versus ibuprofen for the treatment of patent ductus arteriosus

Brian C Gulack  1 , Matthew M Laughon  2 , Reese H Clark  3 , Meera N Sankar  4 , Christoph P Hornik  5 , P Brian Smith  6
Affiliations
Comparative Study

Comparative effectiveness and safety of indomethacin versus ibuprofen for the treatment of patent ductus arteriosus

Brian C Gulack et al. Early Hum Dev. 2015 Dec.

Abstract

Background: Patent ductus arteriosus (PDA) is common in extremely premature infants and associated with increased morbidity and mortality. Medical management of PDA uses either indomethacin or ibuprofen. Despite numerous studies, uncertainty exists as to which drug is safer or more effective; we sought to fill this knowledge gap.

Methods: We identified infants <28weeks gestational age discharged from neonatal intensive care units included in the Pediatrix Medical Group Clinical Data Warehouse between 2006 and 2012 who were treated with indomethacin or ibuprofen between postnatal days 2 and 14. Infants treated with both drugs or infants with a congenital malformation were excluded. We used multivariable logistic regression to determine the association of indomethacin versus ibuprofen on clinical outcomes.

Results: Of 6349 patients who met study criteria, 1177 (19%) received ibuprofen and 5172 (81%) received indomethacin. The median gestational age was 25weeks (interquartile range 24-26), and 2894 (46%) infants were <750g at birth. On unadjusted analysis, infants who received ibuprofen had significantly higher incidences of death prior to discharge, surgical ligation of the PDA prior to discharge, death or spontaneous intestinal perforation within 7days of therapy, death or surgical ligation of the PDA prior to discharge, and an elevated creatinine within 7days of treatment. However, on multivariable analysis, no significant differences in outcomes were observed (odds ratio for death/PDA ligation for ibuprofen vs. indomethacin=1.12 [95% CI 0.91-1.39]).

Conclusions: We observed similar effectiveness and safety profiles for indomethacin and ibuprofen in the medical management of PDA in premature infants.

Keywords: Bronchopulmonary dysplasia; Medical management; Mortality; Premature infants.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: The authors have no potential conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Study cohort. DOL, day of life.
Fig. 2
Fig. 2
Ibuprofen and indomethacin use between 2006 and 2012.
Fig. 3
Fig. 3
Variability in the use of ibuprofen and indomethacin among the 125 sites that treated 10 or more infants over the study period.
See this image and copyright information in PMC

References

    1. Rudolph AM. The changes in the circulation after birth. Their importance in congenital heart disease. Circulation. 1970;41:343–59. - PubMed
    1. Smith GC. The pharmacology of the ductus arteriosus. Pharmacol Rev. 1998;50:35–58. - PubMed
    1. Heymann MA, Rudolph AM. Control of the ductus arteriosus. Physiol Rev. 1975;55:62–78. - PubMed
    1. Campbell M. Natural history of persistent ductus arteriosus. Br Heart J. 1968;30:4–13. - PMC - PubMed
    1. Friedman WF, Hirschklau MJ, Printz MP, Pitlick PT, Kirkpatrick SE. Pharmacologic closure of patent ductus arteriosus in the premature infant. N Engl J Med. 1976;295:526–9. - PubMed

Publication types