Oral drugs used to treat persistent pulmonary hypertension of the newborn

Abstract

Introduction:Persistent Pulmonary Hypertension of the Newborn (PPHN) is a life-threatening neonatal condition, mostly treated with inhaled nitric oxide (iNO), intravenous prostaglandins, oral bosentan, sildenafil and tadalafil. However, the utility of non-oral agents is limited in PPHN for their side effects and inconvenient deliveries. Therefore, oral agents such as bosentan, sildenafil and tadalafil are becoming appealing for their satisfactory efficacy, easy mode of administration and acceptable side effects. Areas covered: We conducted a comprehensive search on Pubmed, Scopus, Web of Sciences concerning the use of bosentan, sildenafil and tadalafil to treat PPHN and summarized their efficacy, safety and pharmacokinetics. Expert opinion: Current randomized controlled trials (RCTs) have demonstrated the favorable responses and tolerable side effects of bosentan and sildenafil. Nevertheless, those RCTs are small and only one study has described the pharmacokinetics of sildenafil in neonates. Accordingly, bosentan, sildenafil and tadalafil remain off-label in clinical use. More well-designed RCTs with large samples and long-term follow-up and pharmacometrics studies are needed to demonstrate the efficacy, safety and pharmacokinetics of bosentan, sildenafil and tadalafil in PPHN.

Keywords: Bosentan; efficacy; persistent pulmonary hypertension of the newborn pharmacokinetics; safety; sildenafil; tadalafil.