During a PTN-hosted symposium at the annual Pediatric Academic Societies (PAS) Meeting on Sunday, April 28, Dr. Kelly Wade of the Children’s Hospital of Philadelphia and Dr. Matthew Laughon of the University of North Carolina at Chapel Hill shared how PTN’s work is informing on the doses of medications commonly given to infants in the neonatal intensive care unit (NICU).
While improved survival of the smallest, most premature babies is a victory for health care, Dr. Wade said, it also presents a challenge: ensuring a safe passage through a sometimes months-long stay in the NICU. This stay often involves a number of medications that are prescribed “off-label,” or without specific safety and dosing information for this particular – and very vulnerable – population. The NICU, she said, presents a unique opportunity to study these medications in the youngest patients to learn how to dose them appropriately and, consequently, improve their outcomes.
According to a PTN publication, 65 percent of the top 100 most commonly prescribed medications are not adequately studied or labeled for use in the NICU. The PTN is making it a priority to study a number of these drugs, especially “top-10” drugs such as ampicillin, furosemide, and caffeine. These three medications alone, Dr. Laughon said, represent 80 percent of off-label use in the NICU.
“The PTN is really going for these high-effect, high-impact type studies,” he said.
Since this population is so vulnerable, however, there are a number of challenges to enrolling babies in these studies. Dr. Laughon listed a number of measures that the PTN has put in place to make sure the studies are minimally burdensome on these children and their families.
“The blood sampling is aligned with standard of care to prevent extra needle sticks, smaller blood volumes are taken, and sometimes we’re able to measure two or more drugs in a single sample,” he said.
Drs. Wade and Laughon pointed out the wide variation in dosing of ampicillin, the most commonly used drug in the NICU. To ensure infants were getting the safest and most effective dose of this drug, PTN did a study of 73 babies that used standard of care dosing. The results of the study indicated that the most common dose used in clinical care is probably too high, and that high doses of ampicillin may increase the risk of seizures.
Dr. Laughon added that there are currently no FDA-indicated therapies for the prevention or treatment of bronchopulmonary dysplasia (BPD), a chronic lung disease that affects mostly preterm and term infants. The PTN is conducting a randomized study that has enrolled 80 participants so far to determine the appropriate dose of furosemide, the top diuretic used to treat BPD.
In addition to studying these medications, PTN work has led to recent label changes for meropenem for intra-abdominal infections and acyclovir for herpes simplex infection. Data are also currently at the FDA to support label changes for piperacillin-tazobactam and fluconazole, and are currently being collected for anti-staph antibiotics, furosemide, sildenafil, and timolol for the treatment of infantile hemangiomas (often called strawberry birthmarks).
“We still have a lot of work to do to understand what’s the best dose to provide the optimal response,” Dr. Wade said.