Furosemide

Furosemide Safety in Preterm Infants at Risk for Bronchopulmonary Dysplasia: A Randomized Clinical Trial

Posted on by Jeannine Sato

The Journal of Pediatrics • April 2025

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Greenberg RG, Lang J, Smith PB, Shekhawat P, Courtney SE, Hudak ML, Moya F, Iyengar A, Eldemerdash A, Bloom B, Go M, Hanna M, Rhein L, Aliaga S, Lewis T, Febre A, Kiefer AS, Bhatt-Mehta V, Khoury JA, Selewski D, Anand R, Martz K, Payne EH, Zimmerman KO, Benjamin DK Jr, Laughon M; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee.

The objective of this study was to evaluate the safety of furosemide in preterm infants at the risk of developing bronchopulmonary dysplasia (BPD). This multicenter, randomized, dose-escalating, placebo-controlled trial enrolled infants born <29 weeks gestational age at 7-28 days postnatal age and at risk for BPD. In preterm infants, furosemide did not increase the overall incidence of AEs, hearing loss, or nephrocalcinosis, but did increase the incidence of electrolyte abnormalities. Furosemide given for 28 consecutive days was not associated with a difference in moderate-to-severe BPD or death at 36 weeks postmenstrual age.

Medication Use in the Neonatal Intensive Care Unit and Changes from 2010 to 2018

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • January 2022

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Stark A, Smith PB, Hornik CP, Zimmerman KO, Hornik CD, Pradeep S, Clark RH, Benjamin DK, Laughon M, Greenberg RG.

The goal of this study was to provide up-to-date medication prescribing patterns in US neonatal intensive care units (NICUs) and to examine trends in prescribing patterns over time. The most frequently prescribed medications included ampicillin, gentamicin, caffeine citrate, poractant alfa, morphine, vancomycin, furosemide, fentanyl, midazolam, and acetaminophen. Of the top 50 medications used in infants with extremely low birth weight, only 20 (40%) are FDA-labeled for use in infants. Trends of medication use in the NICU change substantially over time. It is imperative to identify changes in medication use in the NICU to better inform further prospective studies.

Furosemide Exposure and Prevention of Bronchopulmonary Dysplasia in Premature Infants

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • May 2019

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Greenberg RG, Gayam S, Savage D, Tong A, Gorham D, Sholomon A, Clark RH, Benjamin DK, Laughon M, Smith PB

The goal of this study was to evaluate the association between furosemide exposure and risk of bronchopulmonary dysplasia (BPD) for premature infants. More days of furosemide exposure between postnatal day 7 and 36 weeks was associated with decreased risk of BPD and a combined outcome of BPD or death.

Prolonged furosemide exposure and risk of abnormal newborn hearing screen in premature infants

Posted on by Kayla Korzekwinski

Early Human Development • October 2018

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Wang LA, Smith PB, Laughon M, Goldberg RN, Ku LC, Zimmerman KO, Balevic S, Clark RH, Benjamin DK, Greenberg RG; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee.

At very high doses, furosemide is linked to ototoxicity in adults, but little is known about the risk of hearing loss in premature infants exposed to furosemide. Our aim was to evaluate the association between prolonged furosemide exposure and abnormal hearing screening in premature infants.

Association between Furosemide Exposure and Patent Ductus Arteriosus in Hospitalized Infants of Very Low Birth Weight

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • August 2018

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Thompson EJ, Greenberg RG, Kumar K, Laughon M, Smith PB, Clark RH, Crowell A, Shaw L, Harrison L, Scales G, Bell N, Hornik CP

This study evaluated the association between furosemide exposure and patent ductus arteriosus (PDA) in a large, contemporary cohort of hospitalized infants with very low birth weight (VLBW). Furosemide exposure was not associated with increased odds of PDA treatment in hospitalized infants of VLBW. Further studies are needed to characterize the efficacy and safety of furosemide in premature infants.

Diuretic Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia

Assessing the safety and preliminary effectiveness of furosemide, which is often used to prevent bronchopulmonary dysplasia, in premature infants.

Summary

More than 60,000 infants are born ≤29 weeks gestational age each year in the United States, and nearly 40% of those develop bronchopulmonary dysplasia (BPD). Because the consequences of BPD can be catastrophic, neonatologists frequently use diuretics such as furosemide to reduce pulmonary edema, improve pulmonary mechanics, minimize exposure to mechanical ventilation, and, ultimately, to prevent BPD. The understanding of the safety profile of furosemide in premature infants, however, is limited.

The PTN is conducting a phase 2, randomized, multicenter, placebo-controlled, dose-escalating, double-masked safety study to evaluate the safety and preliminary effectiveness of furosemide in premature infants at risk of BPD. Approximately 120 infants will be enrolled at ~30 sites. Total duration of study participation is 35 days (28 days of treatment and 7 days of safety monitoring).

Publications

 

OVERVIEW

Status:
Enrolling

ClinicalTrials.gov identifier:
NCT02527798

NICHD Data and Specimen Hub (DASH):
Infants Exposed to Furosemide or Bumetanide

Principal Investigators:
Matthew Laughon, MD, MPH
University of North Carolina
Chapel Hill, NC

P. Brian Smith, MD, MPH, MHS
Duke Health, Durham, NC

Label Change

  • Based on PK results obtained from 51 premature infants (23-29 weeks gestational age (GA)) receiving repeated doses up to 4 times the maximum recommended total daily dose for intravenous (IV) administration (or 8 times the maximum recommended total daily dose for enteral administration), body weight and postnatal age were found to have an impact on furosemide clearance.
  • Median clearance (normalized by dosing weight) was observed to increase from 8.9 (range: 2.1-21.2) ml/h/kg in infants with postnatal age (PNA) <30 days to 25.3 (range: 8.3 to 44.2) ml/h/kg in infants with PNA >30 days.
  • In addition, higher clearance was observed in infants with higher body weight. Bioavailability of enteral dose compared to IV dose was estimated to be around 79%.

 

NEWS

    Comparative effectiveness of 3 surfactant preparations in premature infants

    Posted on by Kayla Korzekwinski

    Journal of Pediatrics • October 2013

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    Trembath A, Hornik CP, Clark R, Smith PB, Daniels J, Laughon M; Best Pharmaceuticals for Children Act—Pediatric Trials Network.

    To compare effectiveness of 3 surfactant preparations (beractant, calfactant, and poractant alfa) in premature infants for preventing 3 outcomes: (1) air leak syndromes; (2) death; and (3) bronchopulmonary dysplasia (BPD) or death (composite outcome).