Table 3.
Pharmacotherapy of BPD-PH.
| Drug | Mechanism | Comment |
|---|---|---|
| Sildenafil | PDE5 inhibitor | Most widely used in BPD-PH. Aggravates gastroesophageal reflux. EMA approved for children >1 year. The EPPVDN consensus (2019) recommends sildenafil at a maximum dose of 1 mg/kg/dose every 6 h in the first year of life, followed by the EMA drug recommendations for sildenafil: 10 mg every 8 h for patients ≥10 kg bodyweight and >12 months old, and 20 mg every 8 h for patients ≥20 kg bodyweight) |
| Tadalafil | PDE5 inhibitor | Alternative to sildenafil, less frequent dosing. No data on BPD-PH |
| Riociguat | Stimulator of soluble guanylatcyclase (sGC) | “Dual” mode of action (sGC activator and stimulator). No data on BPD-PH |
| Bosentan | ERA |
ET1A- and ET1B-receptor antagonist. Most widely used in BPD-PH in combination with PDE-5 inhibitor. May increase liver transaminases. Lowers circulating sildenafil levels. EMA approved for children with PAH >1 year based on BREATHE-3 and FUTURE-1 trials FDA-approved for children with PAH >3 years Maximum target bosentan dose is 2 mg/kg body weight twice daily (4 mg/kg/day) |
| Macitentan | ERA | ET1A- und ET1B-receptor antagonist. No liver toxicity. Does not lower sildenafil levels. Only limited experience in BPD-PH |
| Ambrisentan | ERA | Selective ET1A-receptor inhibition. May increase liver transaminases. Does not lower sildenafil levels. No experience in BPD-PH |
| Iloprost | PCA | Some experience in infants with PPHN and CHD-PAH either in combination with sildenafil or as monotherapy. May cause airway hyperreactivity |
| Epoprostenol | PCA | No experience in BPD-PH |
| Trepostinil | PCA | No experience in BPD-PH |
| Selexipag | Oral IP-receptor agonist | Only few reports on pediatric use in PAH, and CHD-PAH. Offers potential of oral “triple”-combination therapy. See EPPVDN pediatric selexipag study (2020)43 |
BPD-PH bronchopulmonary dysplasia-associated pulmonary hypertension, CHD congenital heart disease, EMA European Medicines Agency, ERA endothelin receptor antagonist, ET endothelin, IP prostacyclin receptor, PDE5 phosphodiesterase 5, PAH pulmonary arterial hypertension, PCA prostacyclin analog, PPHN persistent pulmonary hypertension of the newborn, FDA Food and Drug Administration.