Sildenafil

Safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia: Rationale and methods of a phase II randomized trial

Posted on by Kayla Korzekwinski

Contemporary Clinical Trials Communications • December 2022

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Lang JE, Hornik CD, Martz K, Jacangelo J, Anand R, Greenberg R, Hornik C, Zimmerman K, Smith PB, Benjamin DK, Laughon M
Bronchopulmonary dysplasia (BPD) is a disease of chronic respiratory insufficiency stemming from premature birth and iatrogenic lung injury leading to many complications. BPD is the most common pulmonary sequela of prematurity and is often fatal; however, there remains no FDA-approved therapies to treat or prevent BPD. Sildenafil is increasingly used off-label in premature infants despite scant safety and efficacy data. We developed the phase II SIL02 trial to describe the safety, pharmacokinetics and preliminary effectiveness of intravenous and enteral sildenafil in premature infants at risk for BPD.

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

Posted on by Kayla Korzekwinski

Journal of Perinatology • January 2022

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Jackson W, Gonzalez D, Smith PB, Ambalavanan N, Atz A, Sokol GM, Hornik CD, Stewart D, Mundakel G, Poindexter BB, Ahlfeld SK, Mills M, Cohen-Wolkowiez M, Martz K, Hornik CP, Laughon MM; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
This study sought to characterize the safety of sildenafil in premature infants. Safety was evaluated based on adverse events (AEs), transaminase levels, and mean arterial pressure monitoring. There was one serious AE related to the study drug involving hypotension associated with a faster infusion rate than specified by the protocol. There were no AEs related to elevated transaminases. 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.

Physiologically-Based Pharmacokinetic Modeling Characterizes the CYP3A-Mediated Drug-Drug Interaction Between Fluconazole and Sildenafil in Infants

Posted on by Kayla Korzekwinski

Clinical Pharmacology & Therapeutics • January 2021

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Salerno SN, Edginton A, Gerhart JG, Laughon MM, Ambalavanan N, Sokol GM, Hornik CD, Stewart D, Mills M, Martz K, Gonzalez D; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
Infants being treated for pulmonary hypertension and prevention or treatment of invasive candidiasis may be given sildenafil with fluconazole concurrently. Physiologically-based pharmacokinetic (PBPK) modeling can potentially predict pediatric drug-drug interactions (DDIs) when clinical DDI data are limited. This study highlights the feasibility of PBPK modeling to predict DDIs in infants and the need to include CYP3A7 parameters.

Population pharmacokinetics of sildenafil in extremely premature infants

Posted on by Kayla Korzekwinski

British Journal of Clinical Pharmacology • December 2019

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Gonzalez D, Laughon MM, Smith PB, Ge S, Ambalavanan N, Atz A, Sokol GM, Hornik CD, Stewart D, Mundakel G, Poindexter BB, Gaedigk R, Mills M, Cohen-Wolkowiez M, Martz K, Hornik CP

We performed a multicentre, open-label trial to characterize the pharmacokinetics (PK) of sildenafil in infants ≤28 weeks gestation and < 365 postnatal days (cohort 1) or < 32 weeks gestation and 3-42 postnatal days (cohort 2). We successfully characterized the PK of sildenafil and DMS in premature infants and applied the model to inform dosing for a follow-up, phase II study.

Sildenafil Exposure in the Neonatal Intensive Care Unit

Posted on by Kayla Korzekwinski

American Journal of Perinatology • February 2019

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Thompson EJ, Perez K, Hornik CP, Smith PB, Clark RH, Laughon M; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee

Pulmonary hypertension causes substantial morbidity and mortality in infants. Although Food and Drug Administration approved to treat pulmonary arterial hypertension in adults, sildenafil is not approved for infants. This study sought to describe sildenafil exposure and associated diagnoses and outcomes in infants.

Sildenafil and retinopathy of prematurity risk in very low birth weight infants

Posted on by Kayla Korzekwinski

American Journal of Perinatology • February 2016

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Samiee-Zafarghandy S, van den Anker JN, Laughon MM, Clark RH, Smith PB, Hornik CP; Pharmaceuticals for Children Act – Pediatric Trials Network Administrative Core Committee.

We identified premature infants who were discharged from Pediatrix Medical Group neonatal intensive care units from 2003–2012 and who received an ophthalmologic exam. We matched each infant exposed to sildenafil prior to first eye exam to three non-exposed infants using propensity scoring to control for differences in baseline infant characteristics. We evaluated the association between sildenafil exposure and development of severe ROP using conditional logistic regression.