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, 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

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.

Conflict of interest statement

The authors declare no competing interests.

© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

Figures

Fig. 1. Change from baseline Mean Arterial…
Fig. 1. Change from baseline Mean Arterial Pressure (MAP) over time following start of IV sildenafil infusion.
a The dose group 0.25 mg/kg and b dose group 0.125 mg/kg in a phase I study of sildenafil in premature infants. Circles represent median change and whiskers represent minimum and maximum value.

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Source: PubMed

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