15th International Conference

Neonatal & Childhood Pulmonary Vascular Disease

San Fancisco, California

February 24th - 26th, 2022

 

Video Presentation

Hear directly from Kurt Bjorkman, MD about this study.

 

The prostacyclin receptor agonist, selexipag, provides an oral option targeting the prostacyclin pathway as a part of triple-therapy for pulmonary arterial hypertension (PAH) with common combinations of a phosphodiesterase 5 inhibitor and an endothelin receptor antagonist. The aim was to review selexipag dosing in young children and infants, as guidelines have not been established for this group.

We reviewed all published literature and our center’s experience on selexipag use in children < 5 years old. Patient characteristics were recorded including diagnoses, dosing strategies, additional medication regimens, outcomes, and adverse events.

Seven published works were reviewed with 35 total patients -- 8 who initiated therapy < 5 years of age. An additional patient at our institution was diagnosed with pulmonary arterial hypertension and treated with Selexipag at age < 5 years and included in this data analysis.

Case Presentation

An additional patient at our institution was diagnosed with heritable-PAH (heterozygous ACVRL1) -- baseline reduced right ventricular (RV) function, NTproBNP 32,869pg/mL, supra-systemic RV systolic pressure (RVSP) by cath and echo-estimated tricuspid valve regurgitation velocity, and pulmonary vascular resistance 44.3 woods units*m2. Pulmonary vasodilator therapy was initiated and increased to sildenafil 1mg/kg three times daily, bosentan 2mg/kg twice daily, and subcutaneous treprostinil 120ng/kg/min with improvement of RVSP to ½ systemic and normalization of RV function and NTproBNP. At 2 years 8 months old,12.4kg and BSA 0.5m2, Treprostinil was gradually weaned to 70ng/kg/min prior to planned transition to oral selexipag for ease of at-home medical management. He started selexipag 100µg twice daily and increased to 600µg dosing with wean off treprostinil, experiencing symptoms of jaw pain, headaches, and diarrhea. Dosing was decreased to 500µg (40µg/kg), and adverse symptoms resolved. On follow-up, NTproBNP remained normal (122pg/mL), and echo demonstrated stable RVSP near ½ systemic pressure.

Table 1: Individual PAH patient characteristics and medication regimens at the time of selexipag start.

* Patients # 1-6 from Hansmann et al 2020, #7 from Rothman et al 2020, #8 from Koo et al 2019, #9 treated at our center.

** First dose means the very first starting dose. Final dose means here the long-term dose achieved with acceptable adverse effects. All dosing administered enterally twice a day.

± 16 months after initiation of SEL

Abbreviations: AEs, adverse events; AML, amlodipine; ASA, acetylsalicylic acid; (P.O.); ASD, atrial septal defect; BSA, body surface area; BOS, bosentan (P.O.); BPD, bronchopulmonary dysplasia; CHD, congenital heart disease; FC, functional class; FUR, furosemide (Lasix) (P.O.); HPAH, heritable PAH; IPAH, idiopathic PAH (WPSH 2018 category 1.1); LuTx, lung transplantation; MAC,macitentan (P.O.); PAH, pulmonary arterial hypertension; PDA, patent ductus arteriosus; PFO, patent foramen ovale; PH, pulmonary hypertension; SIL, sildenafil (P.O.); SPI, spironolactone, TREP, treprostinil; VSD, ventricular septal defect

Conclusion

This review of selexipag use in children < 5 years old for treatment of PAH shows max dosing with acceptable outcomes and side effects between 40-70µg/kg twice daily.

  • References

    Geerdink LM, Bertam H, Hansmann G. First-in-child use of the oral selective prostacyclin IP receptor agonist selexipag in pulmonary arterial hypertension. Pulm Circ 2017; 7: 551–554.

    Gallotti R, Drigalis-Kim, DE Satou, G, et al. Single-center experience using selexipag in a pediatric population. Pediatr Cardiol 2017; 38: 1405–1409

    Koo R, Lo J, Bock MJ. Transition from intravenous treprostinil to enteral selexipag in an infant with pulmonary arterial hypertension. Cardiol in the Young 2019; 29(6): 849-851.

    Rothman R, Cruz G, Evans W, Restrepo H. Hemodynamic and clinical effects of selexipag in children with pulmonary hypertension. Pulm Circ 2020; 10: 1-7.

    Hansmann G, Meinel K, Bukova M, Chouvarine P, Wåhlander H, Koestenberger M, & Network, E. P. P. V. D. Selexipag for the treatment of children with pulmonary arterial hypertension: First multicenter experience in drug safety and efficacy. J of Heart & Lung Transp 2020; 39(7): 695-706.

    Colglazier E, Ng AJ, Parker C, Nawaytou H, Fineman JR. Safety and Tolerability of a Rapid Transition From Intravenous Treprostinil to Oral Selexipag in Three Adolescent Patients With Pulmonary Arterial Hypertension. J of Ped Pharm & Therap 2021; 26(5): 512-516.

    Bravo-Valenzuela, Nathalie Jeanne Magioli, Flavia Navarro, and Socrates Pereira Silva. "Use of selexipag in a teenage patient with pulmonary arterial hypertension." Annals of Ped Cardiol 2021;14(1): 75.