Pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants

Cardiology in the Young January 2025

Access article on PubMed.

Kumar KR, Ciociola EC, Skinner KR, Dixit GM, Alvarez S, Benjamin EK, Faulkner JC, Greenberg RG, Clark RH, Benjamin Jr DK, Hornik CP and Jan Hau Lee

New drugs to target different pathways in pulmonary hypertension have resulted in increased combination therapy, but details of this use in infants are not well described. This large multicenter database study describes the pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants. The study revealed an increased use of combination pulmonary vasodilator therapy, favouring inhaled nitric oxide and sildenafil, yet with considerable practice variation. Further research is needed to determine the optimal combination, sequence, dosing, and disease-specific indications for combination therapy.

Population Pharmacokinetics of Milrinone in Infants, Children, and Adolescents

Journal of Clinical Pharmacology • December 2019

Access article on PubMed.

Hornik CP, Yogev R, Mourani PM, Watt KM, Sullivan JE, Atz AM, Speicher D, Al-Uzri A, Adu-Darko M, Payne E, Gelber C, Lin S, Harper B, Melloni C, Cohen-Wolkowiez M, Gonzalez D

Milrinone is a type 3 phosphodiesterase inhibitor used to improve cardiac output in critically ill infants and children. Milrinone is primarily excreted unchanged in the urine, raising concerns for toxic accumulation in the setting of renal dysfunction of critical illness. We developed a population pharmacokinetic model of milrinone using nonlinear mixed-effects modeling in NONMEM to perform dose-exposure simulations in children with variable renal function. Children below 21 years of age were included.

Sildenafil Exposure in the Neonatal Intensive Care Unit

American Journal of Perinatology February 2019

Access article on PubMed.

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

American Journal of Perinatology • February 2016

Access article on PubMed.

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.

Safety of milrinone use in neonatal intensive care units

Early Human Development • January 2015

Access article on PubMed.

Samiee-Zafarghandy S, Raman SR, van den Anker JN, McHutchison K, Hornik CP, Clark RH, Smith PB; Best Pharmaceuticals for Children Act—Pediatric Trials Network Administrative Core Committee.

Milrinone use in the neonatal intensive care unit has increased over the last 10 years despite a paucity of published safety data in infants. We sought to determine the safety of milrinone therapy among infants in the neonatal intensive care unit. We conducted a retrospective data analysis, identifying all infants who were exposed to milrinone and discharged from 322 neonatal intensive care units managed by the Pediatrix Medical Group from 1997-2010.