Safety of Epoprostenol and Treprostinil in Children Less than 12 Months of Age

Abstract

There is a paucity of data on infant intravenous prostacyclin use, the gold standard for therapy for severe pulmonary hypertension (PH). This review aimed to evaluate the safety, tolerability, and outcomes of infant prostacyclin use. A retrospective observational study was performed in a large pediatric hospital with a dedicated pediatric PH program. Subject medical records, bedside flow sheets, and progress notes were reviewed to identify use of intravenous epoprostenol or treprostinil within the first year of life. The indication for prostacyclin use was recalcitrant hemodynamic compromise associated with PH, identified as either idiopathic PH, persistent PH of the newborn, PH associated with congenital diaphragmatic hernia, congenital heart disease, bronchiolitis, or chronic lung disease. Prostacyclin-related adverse events included 7 episodes of hypotension, 6 episodes of perceived pain, 2 episodes of cyanosis, and 1 episode of feeding intolerance. Prostacyclin was stopped only for cyanotic episodes associated with use in severe chronic lung disease. Two hemorrhagic events occurred during extracorporeal membrane oxygenation, which were unlikely to be prostacyclin related. Outcomes included 21 deaths unrelated to prostacyclin, 1 lung transplant, 6 PH resolutions, 8 transitions to oral PH medications, and 1 continuation of treprostinil. In conclusion, efficacy could not be evaluated in this study because of the loss of equipoise for neonatal prostacyclin use. Prostacyclin use was well tolerated in neonatal diseases associated with PH, but dose titration was limited by hypotension and hypoxemia.

Transition from intravenous treprostinil to enteral selexipag in an infant with pulmonary arterial hypertension

“…Although transition to subcutaneous treprostinil before discharge has been successful and is becoming a more viable option in infants receiving prostacyclin therapy, our patient was unable to be discharged on this medication; therefore, the decision to undertake the transition to enteral selexipag was made. [1][2][3] Selexipag is the first in a new generation of long-acting enteral selective prostacyclin IP receptor agonists approved for the treatment of pulmonary arterial hypertension in adults. 4 There have been few reports of its use in the children to date.…”

Análogos de prostaglandinas I2 (epoprostenol y treprostinil) para el tratamiento de la hipertensión pulmonar refractaria secundaria a displasia broncopulmonar en un lactante

“…Aunque nuestro artículo está en consonancia con otras series de casos, 3,13 son necesarios ensayos multicéntricos controlados aleatorizados con seguimiento a largo plazo para establecer la seguridad, la eficacia y las pautas óptimas del treprostinil en pacientes con hipertensión pulmonar. n…”

Treprostinil Attains Clinically Therapeutic Concentrations in Neonates with Pulmonary Hypertension on Extracorporeal Membrane Oxygenation Support

“…Treprostinil, a synthetic prostacyclin analog, is a potent pulmonary vasodilator approved for the treatment of idiopathic pulmonary arterial hypertension in adults and children. 4,5 We and others have reported good tolerance and clinical improvement with treprostinil as off-label, add-on therapy in neonates with PPHN refractory to inhaled nitric oxide (iNO) and sildenafil, [6][7][8][9][10] whereas clinical efficacy is currently investigated in an ongoing placebo-controlled randomized trial as add-on intervention to iNO (NCT02261883). In neonates with severe PPHN enduring persistent hypoxemia and hemodynamic instability despite aggressive medical management, therapy with extracorporeal membrane oxygenation (ECMO) is indicated.…”