Off-label use of prostacyclin therapy successfully treated five newborns with persistent pulmonary hypertension of the neonate (PPHN), and switching from intravenous infusion to subcutaneous injection was well tolerated, a case series reported.
Its authors recommend larger studies to further evaluate the effectiveness and safety of these medications in PPHN infants.
These case reports were described in the study,” Transitioning From Intravenous to Subcutaneous Prostacyclin Therapy in Neonates With Severe Pulmonary Hypertension,” published in The Journal of Pediatric Pharmacology and Therapeutics.
Prostacyclin therapy is commonly prescribed to adults with pulmonary arterial hypertension (PAH). It helps blood vessels relax and widen (vasodilator effect), leading to improved blood flow, breathing, exercise abilities, and survival.
However, little data support prostacyclin therapy in newborns with pulmonary hypertension, also known as PPHN, in which blood vessels of the lungs, which are closed before birth, fail to open after birth and limit blood flow.
Researchers based at St. Joseph’s Hospital and Medical Center in Arizona described the use of prostacyclin therapy in five cases of PPHN, with emphasis on dosing, transitioning between different prostacyclin-based therapies, and routes of administration.
All infants were admitted to a neonatal intensive care unit, given a PPHN diagnosis, and immediately treated with vasodilators — inhaled nitric oxide (iNO) and sildenafil (sold as Revatio by Pfizer). Prostacyclin therapy was started when symptoms did not improve.
The first infant was a female born at 37 weeks gestational age with PPHN, respiratory failure, and an undiagnosed congenital diaphragmatic hernia (CDH) — when the muscle that separates the chest from the abdomen fails to close during development. (Gestational age between 38 and 42 weeks is considered normal; infants born before 37 weeks are considered premature.)
She was given ventilation, iNO, and extracorporeal membrane oxygenation (ECMO) — the temporary drawing of blood from the body to allow artificial oxygenation. The CDH was repaired by surgery when she was 7 days old, but she was unable to be weaned from ECMO despite further vasodilator treatment.
After almost a month of ECMO, on day 28, she was started on intravenous (IV, into-the-vein) epoprostenol, a synthetic form of prostacyclin (sold as Flolan by GSK, and as Veletri by Actelion Pharmaceuticals).
Within 72 hours, she was weaned from ECMO, then transitioned to IV treprostinil (a synthetic form of prostacyclin sold as Remodulin by United Therapeutics), and later to subcutaneous (under-the-skin) treprostinil injections.
She tolerated the transitions well, with minimum adverse reactions, and was discharged from the hospital when she was 125 days old (just over 4 months old).
The second infant was a male born at 39 weeks gestation with severe CDH and PPHN after delivery, who required intubation and mechanical ventilation. He was started on epoprostenol at 1 day old, and underwent surgery to repair the CDH three days later.
The baby was transitioned to IV treprostinil on day 21, and once stable, switch to subcutaneous treprostinil injections at 24 day old. He tolerated the transition well and was sent home 50 days after his birth.
The third baby was a female born prematurely at 24 weeks gestation. She developed severe respiratory failure, requiring reintubation and ventilation support for about 4.5 months due to chronic lung disease of prematurity.
As she approached 5 months old (142 days), she was started on IV epoprostenol because of severe PAH. The dose was increased until she was transitioned to IV treprostinil. The girl tolerated the transition very well, and started on subcutaneous treprostinil at 158 days old (about 5.3 months). Once stable, she was discharged within a week to a local children’s hospital for further care.
The fourth patient was a female born at 38 weeks gestation with a severe CDH, who developed PPHN and respiratory distress after delivery and was given ECMO. She was immediately started on IV epoprostenol with increased dosing over time, and underwent surgery to correct the CHD at 5 and 15 days old.
Due to bleeding complications, she was transitioned to IV treprostinil, then subcutaneous treprostinil when she was 22 days old. With no adverse events reported, she discharged when she was 2.4 months old (73 days).
The fifth infant was a male born at 33 weeks gestation with severe PPHN and heart abnormalities, including valves that did not close properly. He was intubated with ventilation in the delivery room with increasing breathing support.
He was given IV epoprostenol, and doses increased over time. At 9 days old, he was switched to IV treprostinil, which also increased in dose. Subcutaneous treprostinil was started on day 19, and the boy was sent home when he was about 2.3 months old (69 days). He tolerated both therapy infusions, and transitioned between routes of administration with no adverse events.
Overall, “all patients survived to hospital discharge and were sent home on [subcutaneous] treprostinil. Minimal adverse effects were seen,” the researchers wrote.
These findings demonstrate that “IV and [subcutaneous] prostacyclin therapy is a therapeutic option for PPHN,” the team wrote, noting that “currently, neither epoprostenol nor treprostinil is approved in neonates for the treatment of pulmonary hypertension, leaving very few treatment options in the neonatal population.”
Larger studies “further evaluating the safety and efficacy of these medications in this population are warranted,” they added.
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