Journal of Pediatric Pharmacology and Therapeutics最新文献

Objective: Tranexamic acid (TXA) is a vital hemostatic agent in pediatric medicine, demonstrating substantial efficacy in managing both traumatic and nontraumatic hemorrhage. Although TXA has been widely adopted in adult trauma and surgical care, reducing mortality, minimizing transfusion requirements, and controlling perioperative and emergency-related bleeding, its pediatric use remains under researched, with knowledge gaps in optimal dosing, long-term safety, and thromboembolic risks. Pediatric-specific clinical guidelines remain inconsistent, necessitating further research on their role in pediatric emergency and perioperative care.

Methods: A targeted literature search using a combination of MeSH terms and keywords was conducted using PubMed and Google Scholar, covering relevant studies focusing on the efficacy, pharmacokinetics, dosing strategies, and safety profile of TXA in children (ages 0-18 years) published between 1995 and February 2025.

Results: Evidence supports the efficacy of TXA in reducing blood loss, minimizing transfusion needs, and improving survival outcomes in pediatric trauma, surgery, and emergency settings. Alternative administration routes, such as nebulized TXA, show promise for post-tonsillectomy hemorrhage and refractory epistaxis, potentially reducing the need for invasive interventions. However, gaps persist regarding age-specific pharmacokinetics, long-term safety, and potential thromboembolic and seizure risks. Inconsistent clinical practice, limited provider familiarity, and a lack of standardized pediatric protocols further hinder the use of TXA in pediatric settings.

Conclusion: TXA remains a critical intervention for improving survival and clinical outcomes in pediatric hemorrhagic emergencies. However, its full potential depends on further interdisciplinary research, the development of standardized pediatric-specific guidelines, and enhanced provider training. Addressing knowledge gaps will be essential to ensuring safe implementation of TXA across diverse pediatric clinical scenarios.

Objective: While most population pharmacokinetic (PopPK) models undergo internal validation, few pediatric PopPK models undergo external evaluation. We aimed to externally evaluate a previously developed PopPK model of caffeine in neonates with congenital heart disease using data collected from a pragmatic platform trial.

Methods: We prospectively enrolled neonates with congenital heart disease who received caffeine per standard of care for prostaglandin-associated apnea and collected opportunistic or scavenged pharmacokinetic samples in a pragmatic platform trial. The predictive performance of the PopPK model was evaluated using model prediction error (PE), mean prediction error (MPE), mean absolute prediction error (MAPE), proportion of predicted values within 20% (F20) and 30% (F30) of observed values, prediction-corrected visual predictive checks, and normalized prediction distribution errors. Dosing simulations were conducted to match exposures seen in preterm infants.

Results: Fourteen neonates contributed 37 pharmacokinetic samples to the validation cohort. The model demonstrated strong quantitative predictive performance (PE -0.18 mg/L, MPE -1.3%, and MAPE 13.3%, F20 79%, and F30 88%), meeting predefined thresholds. Graphical diagnostics supported model accuracy. Dosing simulations revealed lower caffeine exposures in neonates with congenital heart disease, particularly after cardiopulmonary bypass, than in preterm neonates without heart disease.

Conclusions: External evaluation of a pediatric PopPK model using data from a pragmatic platform trial was successful. Our external evaluation supports broader adoption of pragmatic platform trials for pediatric model development and evaluation. These studies can inform starting doses for future trials, which cannot necessarily be extrapolated from other populations due to variability in drug disposition.

Objective: Currently, there is limited information regarding the effect of a pharmacy-managed medication reconciliation program for pediatric behavioral health patients admitted to an inpatient service through a pediatric emergency department. This research aimed to determine the impact of a pediatric behavioral health medication reconciliation program in a regional tertiary care pediatric emergency department.

Methods: This retrospective, single-center analysis evaluated the implementation of a medication reconciliation program in the pediatric behavioral health population using a pre-post design. We compared the quantity of pharmacy-initiated admission medication reconciliation interventions, the time to completion of admission medication reconciliations, and the trends in completion rates for a 2-month period before (October 1, 2022, to November 30, 2022) and after implementation (October 1, 2023, to November 30, 2023).

Results: A total of 107 patients were included, 59 in the pre-intervention group and 48 in the post-intervention group. Between the pre-intervention and post-intervention groups, the post-intervention group had a statistically significantly higher number of interventions by pharmacists (61 vs 129, p < 0.0001). The most common pharmacy intervention made in the post-intervention group was discontinuation of the medication order. The average time to completion of admission medication reconciliation increased from 16.33 hours in the pre-intervention group to 38.47 hours in the post-intervention group (p = 0.002).

Conclusions: Implementing a medication reconciliation program in the pediatric behavioral health population admitted through a pediatric emergency department has the potential to increase the quantity of medication discrepancies identified. Time to completion of medication reconciliation increased significantly in the post-intervention group.

This article provides a summary of the Sumner Yaffe Award lecture presented at the annual meeting of the Pediatric Pharmacy Association in Portland, Oregon, on April 10, 2025. The article provides a short history of pediatric clinical pharmacology and elaborates on the ongoing paradox of precision medicine and the drug development process that is still geared toward the labeling of doses for the average patient. The article highlights contemporary clinical decision support approaches that integrate model-informed precision dosing (MIPD) to improve treatment outcomes in children. A series of case studies of successful implementation of model-informed clinical decision support tools is described including examples of full integration of such platforms into the electronic health record at Cincinnati Children's Hospital Medical Center. These studies show that pediatric precision dosing is progressing beyond the conceptual and proof-of-concept stages toward implementation into clinical workflows. The evidence provided indicates that model-informed therapeutic drug management for children is clinically feasible, with an increasing number of studies documenting improved clinical outcomes as compared with standard of care.

Objective: Valganciclovir is an antiviral used to prevent CMV infection. The optimal dosing strategy remains uncertain as manufacturer and weight-based dosing strategies exist. This study aims to define the risk of CMV breakthrough using a weight-based dosing approach for valganciclovir.

Methods: This is a retrospective, single-center study. All patients who received a heart transplant at <18 years of age from January 2011 to August 2022 and were initiated on valganciclovir prophylaxis were eligible for inclusion. Patients were excluded if they required cardiac re-transplantation. The primary outcome was the incidence of CMV breakthrough on a weight-based dose. Secondary outcomes included median difference in daily dose between 2 dosing strategies, incidence of CMV disease, and adverse events.

Results: Thirty-four patients met eligibility for inclusion. The median age at transplant was 3.45 years (range, 0.07-16.87). Thirty-three patients were high- or intermediate-risk for CMV infection. There was no difference in initial valganciclovir dose in patients with CMV breakthrough compared with those without (median: 23.9 mg/kg vs 23.6 mg/kg, p = 0.238). The median weight-based total daily dose (23.9 mg/kg) was found to be significantly lower than the median manufacturer-recommended dose (34.3 mg/kg) (p < 0.001). This study found no significant difference in the daily dose of valganciclovir in patients with and without CMV breakthrough. Use of the manufacturer's equation for the initial dosing regimen produced significantly higher daily doses.

Conclusions: This study's findings suggest implementation of a standard dosing procedure may be useful in optimizing prophylaxis with valganciclovir.

Objective: Owing to a rise in potentially serious errors with parenteral prostacyclin infusions associated with using an unfamiliar MedFusion 3500 syringe pump (MedFusion), we implemented a comprehensive continuous process improvement (CPI) project to increase the overall safety of prostacyclins. The objective of this report was to describe the project's methodology and assess its impact on the number of errors.

Methods: A multidisciplinary team targeted 3 error-prone phases of prostacyclin delivery-ordering, preparation and dispensing, and administration-with CPI between January and October 2019. CPI involved standardizing the ordering process in the electronic health record, fully using the safety features of the MedFusion syringe pump, developing an electronically accessible job aid, and providing ongoing bedside education. A retrospective analysis of errors related to prostacyclin infusion was conducted from January 2013 to December 2023, covering both periods before and after CPI completion.

Results: Before CPI, there were 1471 days of prostacyclins and 27 errors, or 1.8 per 100 patient days. After CPI, there were 1512 days of prostacyclins and 5 errors, or 0.3 per 100 patient days. After CPI, the age at start of infusion was lower, and the average length of infusion increased.

Conclusions: Our multidisciplinary comprehensive CPI decreased errors associated with prostacyclin infusions on the MedFusion pump, and continuous efforts have maintained low error rates.

Objective: The primary objective of this study was to evaluate the number of late pre-term and term neonates who were able to wean off oxygen after receiving short-course prednisolone therapy.

Methods: A retrospective review of prednisolone treatment in oxygen-dependent infants was performed on infants admitted to the neonatal intensive care unit (NICU) at Northwest Texas Hospital, Amarillo, Texas, and received oral prednisolone therapy between January 1, 2021, through January 2023. Patients included were born ≥ 34 weeks gestation and received prednisolone therapy for oxygen weaning. Data collection comprised of maternal and infant medical conditions, medications, oxygen requirements, chest x-ray findings, and length of stay. Prednisolone dosing, duration, and reported adverse effects were collected. Descriptive statistics such as mean and median were used to describe patient characteristics and outcomes.

Results: Thirteen of the 26 infants admitted met the inclusion criteria. Seven (53.8%) were successfully weaned to room air; of these, 5 were weaned to room air by the sixth dose of prednisolone. Neonates with meconium-stained amniotic fluid had an 75% success rate (3 out of 4), and those with suspected/diagnosed transient tachypnea of the newborn (TTN) had 57.1% success (4 out of 7 infants).

Conclusions: Prednisolone therapy shows promising efficacy in weaning late pre-term and term infants off oxygen. Future randomized controlled trials are needed to determine the role and optimal prednisolone regimen.

Objective: Treatment plans prescribed for patients diagnosed with rare metabolic genetic disorders have evolved with the expansion of Food and Drug Administration (FDA)-approved therapies. This study aimed to characterize medication and medical formula utilization within a metabolic genetics clinic.

Methods: This was a retrospective cross-sectional study that included patients with a confirmed metabolic genetic disorder. Manual chart review collected patient diagnosis, medication use, medical formula use, and laboratory data. The primary endpoint was to describe medication and medical formula use in this population. The secondary endpoints included laboratory monitoring frequency, medication acquisition needs, and estimated annual cost, determined using the FDA Redbook.

Results: Of the screened patients, 152 of 225 were included. The most common diagnosis was phenylketonuria (n = 63, 41.4%), and most patients were younger than 21 years old (n = 93, 61.2%). Ninety-five patients were prescribed 110 medications, and 62 patients were prescribed 77 medical formulas. Prior authorization was required for 62.7% of medications and 42.9% of medical formulas. Most medications (70%) were dispensed through specialty pharmacy. Laboratory monitoring was required for 89.1% (98/110) of medications, accounting for 94.7% (90/95) of patients. The estimated annual direct cost of medication use exceeded $100,000 in 47.2% (51/108) of patients, while 31.6% (24/76) of medical formulas exceeded an estimated annual cost of $10,000.

Conclusions: This study describes the treatment landscape of patients seen at a metabolic genetics clinic. Most medications require close laboratory monitoring, prior authorization, and specialty pharmacy use. These data highlight an opportunity for clinical pharmacists to impact the safe and effective use of these high-cost medications.