Safety of sildenafil in extremely premature infants: a phase I trial

Wesley Jackson; Daniel Gonzalez; P Brian Smith; Namasivayam Ambalavanan; Andrew M Atz; Gregory M Sokol; Chi D Hornik; Dan Stewart; Gratias Mundakel; Brenda B Poindexter; Shawn K Ahlfeld; Mary Mills; Michael Cohen-Wolkowiez; Karen Martz; Christoph P Hornik; Matthew M Laughon; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee

doi:10.1038/s41372-021-01261-w

Safety of sildenafil in extremely premature infants: a phase I trial

J Perinatol. 2022 Jan;42(1):31-36. doi: 10.1038/s41372-021-01261-w. Epub 2021 Nov 5.

Authors

Wesley Jackson¹, Daniel Gonzalez², P Brian Smith^{3

4}, Namasivayam Ambalavanan⁵, Andrew M Atz⁶, Gregory M Sokol⁷, Chi D Hornik^{3

4}, Dan Stewart⁸, Gratias Mundakel⁹, Brenda B Poindexter¹⁰, Shawn K Ahlfeld¹¹, Mary Mills⁴, Michael Cohen-Wolkowiez^{3

4}, Karen Martz¹², Christoph P Hornik^{3

4}, Matthew M Laughon¹³; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee

Affiliations

¹ Department of Pediatrics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. wesley.jackson@unc.edu.
² Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
³ Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
⁴ Duke Clinical Research Institute, Durham, NC, USA.
⁵ Division of Neonatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
⁶ Department of Pediatrics, Medical University of South Carolina Children's Hospital, Charleston, SC, USA.
⁷ Division of Neonatal-Perinatal Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
⁸ University of Louisville Norton Children's Hospital, Louisville, KY, USA.
⁹ Kings County Hospital Center/SUNY Downstate Medical Center, Brooklyn, NY, USA.
¹⁰ Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, Atlanta, GA, USA.
¹¹ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
¹² The Emmes Company, LLC, Rockville, MD, USA.
¹³ Department of Pediatrics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Abstract

Objective: To characterize the safety of sildenafil in premature infants.

Study design: A phase I, open-label trial of sildenafil in premature infants receiving sildenafil per usual clinical care (cohort 1) or receiving a single IV dose of sildenafil (cohort 2). Safety was evaluated based on adverse events (AEs), transaminase levels, and mean arterial pressure monitoring.

Results: Twenty-four infants in cohort 1 (n = 25) received enteral sildenafil. In cohort 2, infants received a single IV sildenafil dose of 0.25 mg/kg (n = 7) or 0.125 mg/kg (n = 2). In cohort 2, there was one serious AE related to study drug involving hypotension associated with a faster infusion rate than specified by the protocol. There were no AEs related to elevated transaminases.

Conclusion: Sildenafil was well tolerated by the study population. Drug administration times and flush rates require careful attention to prevent infusion-related hypotension associated with faster infusions of IV sildenafil in premature infants.

Clinical trial: ClinicalTrials.gov Identifier: NCT01670136.

Publication types

Clinical Trial, Phase I

MeSH terms

Humans
Hypotension* / chemically induced
Hypotension* / drug therapy
Infant, Extremely Premature
Infant, Low Birth Weight
Infant, Newborn
Infant, Premature, Diseases* / drug therapy
Sildenafil Citrate / adverse effects

Safety of sildenafil in extremely premature infants: a phase I trial

Authors

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Abstract

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