| PMC full text: | Expert Opin Pharmacother. Author manuscript; available in PMC 2024 Sep 14. Published in final edited form as: Expert Opin Pharmacother. 2023 Sep-Dec; 24(17): 1875–1886. Published online 2023 Sep 14. doi: 10.1080/14656566.2023.2257598 |
Table 2.
Common Pharmacotherapies for Infants with Pulmonary Arterial Hypertension
| Medication | Routes of Administration | Class | Therapeutic Target | FDA indication | Summary / Trials |
|---|---|---|---|---|---|
| Bosentan | Oral | Endothelin-1 Receptor Antagonist | Off-label in infants; in pediatric patients aged 3 years and older with idiopathic or congenital PAH to improve pulmonary vascular resistance (PVR), which is expected to result in an improvement in exercise ability. | More 2016 (37) - Cochrane review: Two RCTs were included in the Cochrane review. There was inadequate evidence to support the use of oral bosentan. | |
| Ambrisentan and Macitentan | Oral | Endothelin-1 Receptor Antagonist | Infants - Off Label; Adults - Indication for WHO Group 1 pulmonary artery hypertension | May have less hepatotoxicity and drug-drug interactions | |
| Epoprostenol | IV or inhaled | Prostacyclin | Activation of adenylate cyclase and production of cyclic AMP in vascular smooth muscles | Infants - Off Label; Adults - Indication for WHO Group 1 pulmonary artery hypertension | In patients with severe PPHN despite inhaled nitric oxide, about 40% will respond to IV epoprostenol with an average improvement in OI by 11. Ahmad 2018 (45); Short half life of 6 minutes. |
| Iloprost | IV or inhaled | Prostacyclin | Activation of adenylate cyclase and production of cyclic AMP in vascular smooth muscles | Infants - Off Label; Adults - Indication for WHO Group 1 pulmonary artery hypertension | Shown to improve PaO2 and OI in subset of responders (n=12) Verma 2022 (47). |
| Treprostinil | IV, oral, subcutaneous | Prostacyclin | Activation of adenylate cyclase and production of cyclic AMP in vascular smooth muscles | Infants - Off Label; Adults - Indication for WHO Group 1 pulmonary artery hypertension | More stable than epoprostenol with half-life of 3 hours in adults. |
| Prostaglandin E1 | IV | Prostacyclin | Increases cyclic AMP in vascular smooth muscles; promotes ductal patency | PGE1 is indicated for palliative, not definitive, therapy to temporarily maintain the patency of the ductus arteriosus until corrective or palliative surgery can be performed in neonates who have congenital heart defects and who depend upon the patent ductus for survival | In CDH or PPHN can be considered for neonates with severe PPHN but definitive studies of benefit are lacking. |
| Inhaled nitric oxide | Inhalation | Miscellaneous respiratory agent | Activation of guanylate cyclase leading to accumulation of cyclic GMP | Indicated for term and near term (>34 weeks gestation) with hypoxic respiratory failure to improve oxygenation and lower risk of ECMO. Off-label use in premature infants with pulmonary hypertension. | Cochrane meta-analysis found that inhaled nitric oxide at 20 parts per million effective in reducing use of ECMO for acute hypoxic respiratory failure. Risks and benefits unknown in preterm (<34 weeks gestation) populationpie (8, 12). |
| Sildenafil | IV, oral | Phosphodiesterase-5 inhibitors | Inhibits the breakdown of vasodilatory cGMP | Indicated to treat pulmonary arterial hypertension WHO Group 1 in children 1–17 years old. Used off-label to treat lung disease associated pulmonary hypertension (WHO Group 3). | Limited data on treatment for PPHN in resource-limited settings where iNO not available (Kamran, Imam) and as adjunctive therapy to iNO (21, 22). Safety and efficacy for treatment of WHO Group 1 PH in pediatric population older than 1 year described in STARTS-1 trial. Limited safety and efficacy data in infants born premature with BPD-related PH. |
| Tadalafil | Oral | Phosphodiesterase-5 inhibitors | Inhibits the breakdown of vasodilatory cGMP | Adults with pulmonary artery hypertension WHO Group 1 | Small trials have shown tadalafil can be used in children (28,29). |
| Milrinone | IV | Inotropic agent; phosphodiesterase inhibitor | Improves cardiac contractility (inotropy), cardiac relaxation (lusitropy), and promotes pulmonary vasodilation through inhibition of phosphodiesterases | Limited data on treatment for PPHN in resource-limited settings where iNO not available and PPHN refractory to iNO (20, 30, 32). Case series in CDH found improved right ventricular function on echo with milrinone (88). | |
| Riociguat | Oral | Soluble guanylate cyclase stimulator | It promotes formation of cGMP and promotes relaxation of the vascular smooth muscle cells | Adults with pulmonary artery hypertension WHO Group 1 and Group 4 | Clinical trials are currently ongoing in children to assess riociguat (NCT 02562235). |