Oral treprostinil use in children: a multicenter, observational experience

Abstract

Pulmonary arterial hypertension is a progressive, incurable disease that occurs in adults and children alike. Therapeutic options for children are limited and infrequently described, including newer agents such as treprostinil, an oral prostanoid. Herein, we describe the pooled pediatric experience in 28 patients from four pediatric pulmonary hypertension programs over two years. This descriptive, observational study describes the various methods of initiation of oral treprostinil in both prostanoid-naïve patients and those transitioning from parenteral or inhaled prostanoids. The youngest patient was four years old and the smallest weighed 16 kg. We describe adverse reactions and their management. Most patients in this study (27/28) were able to successfully initiate therapy. However, gastrointestinal adverse reactions were common; half of the patients started on this therapy had discontinued it within the two-year study period.

Use of Treprostinil in Pediatric Pulmonary Hypertension: Case Reports and Review of the Literature

“…23,29,30 The remaining 16 retrospective studies reported data from small cohorts (1-85 patients), including 1 controlled31 (children with congenital diaphragmatic hernia receiving treprostinil vs. children with congenital diaphragmatic hernia without treprostinil) and 5 multicenter studies. 11,21,[32][33][34] Most authors suggested that treprostinil was an alternative to treat pediatric PH (Table 1). 29,35 However, no data from pediatric randomized controlled trials were reported in the literature, and currently treprostinil has only been approved in adult PAH treatment by European and US drug agencies (Table 2).…”

Opportunities and challenges of pharmacotherapy for pulmonary arterial hypertension in children

“…Treprostinil is also available as extended‐release tablets (trade name, Orenitram®) and has been used in lower risk, stable pediatric PAH patients transitioning from parenteral treprostinil, inhaled treprostinil, or as a new adjunct therapy 62,63 . While the oral route offers many advantages, use of enteral treprostinil in young pediatric patients is limited because the tablets cannot be cut or crushed and must be swallowed whole 64 .…”

“…While the oral route offers many advantages, use of enteral treprostinil in young pediatric patients is limited because the tablets cannot be cut or crushed and must be swallowed whole 64 . Similar to the adult studies, GI side effects like nausea, vomiting, and diarrhea which often can be dose‐limiting, were common among pediatric patients 62,63,65 . To minimize the peak to trough ratio that is theorized to contribute to adverse effects, three‐time a day dosing is recommended over twice‐daily dosing and better mimics continuous parenteral treprostinil concentrations 65,66 .…”

“…Currently, there is an ongoing Phase 2 study investigating the safety, tolerability, and PK of selexipag in PAH patients 2–18 years, weighing at least 9 kg 82 (NCT03492177). Anecdotally, from a GI perspective, selexipag is better tolerated than oral treprostinil 63 . However, there are no well‐established conversions between selexipag and the various prostacyclin formulations 83 (see Table 4 for a summary of reported conversion strategies).…”

The Current Treatments Of Pulmonary Arterial Hypertension

“…The common adverse effects when admitted subcutaneously are infusion site pain and bleeding. Inhaled and oral form of this medication are also available in some countries [36,37].…”