Case Report: Selexipag in pediatric pulmonary hypertension: Initiation, transition, and titration

Abstract

Selexipag, a selective prostacyclin receptor agonist, is approved for treating pulmonary arterial hypertension in WHO Group 1 adult patients. Compared to parenteral prostacyclin formulations, selexipag offers a significant improvement in patient’s and caregiver’s quality of life because of its oral formulation, frequency of administration, and mechanism of action. Although experience in the pediatric population is limited to case reports in older adolescent patients and selexipag is not approved for use in the pediatric pulmonary hypertension population, many pediatric centers are expanding the use of this therapy to this population. We report our institution's experience in the use of selexipag to treat pulmonary hypertension in children under 10 years of age, between 10 and 30 kg. Seven patients were initiated on selexipag therapy including de novo initiation and transition from intravenous treprostinil to oral selexipag. All patients were on stable background therapy with phosphodiesterase-5 inhibitor and endothelin receptor antagonist therapies at baseline. All patients reached their planned goal selexipag dose during admission without the need for changes to the titration schedule and without hemodynamic deterioration. In our experience, oral selexipag is safe and well-tolerated in young pediatric patients with pulmonary hypertension. Based on our favorable experience, we developed an institution-specific selexipag process algorithm for continued successful use in the pediatric population.

Direct prostacyclin transition in pediatric patients with pulmonary hypertension

“…We used preliminary reports that parenteral treprostinil 10 ng/kg/min equaled selexipag 200 mcg twice daily in adults, and 100 mcg twice daily in children. 9 Doses were occasionally adjusted due to concerns for history of prostacyclin side effects. Target end dose of selexipag by mcg twice daily was chosen by weight: 1600 for patients >50 kg, 1200 for patients 25–50 kg, and 800 for patients 9–25 kg.…”

“…Transition dosages chosen were adequate to avoid most side effects and no adverse events occurred. We used preliminary reports that parenteral treprostinil 10 ng/kg/min equaled selexipag 200 mcg twice daily in adults, and 100 mcg twice daily in children 9 . Doses were occasionally adjusted due to concerns for history of prostacyclin side effects.…”

“… 6 , 7 Most “rapid” transitions between prostacyclins and selexipag in pediatric patients take place over 4–8 days, in the hospital. 8 , 9 …”

“…6,7 Most "rapid" transitions between prostacyclins and selexipag in pediatric patients take place over 4-8 days, in the hospital. 8,9 However, transitions over several days in the hospital are inconvenient for patients and families and use limited resources. Our center has previously performed successful rapid 1-day transitions in pediatric PAH patients and hypothesized that transitions with no steps, directly from one prostacyclin to the other, would be as safe and effective as longer transitions.…”

“…As the various treprostinil forms were introduced, reports described transitions using similar stepwise strategies, but with variable length of time, from days up to several weeks, usually longer in outpatient transitions 6,7 . Most “rapid” transitions between prostacyclins and selexipag in pediatric patients take place over 4–8 days, in the hospital 8,9 …”