Journal of Pediatric Pharmacology and Therapeutics最新文献

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.

The prevalence of mental disorders in children and adolescents has increased over the years, along with a rise in the prescription of psychotropic medications in this population. Evidence and drug safety studies in children, however, remain scarce, with many treatments being prescribed off-label. Serotonin syndrome and neuroleptic malignant syndrome are both potentially life-threatening conditions associated with the use of psychotropic medications, with symptoms frequently overlapping. This case report describes a mixed presentation of serotonin syndrome and neuroleptic malignant syndrome in a 12-year-old female patient receiving combined treatment with fluoxetine and haloperidol. She presented with intermittent generalized muscle rigidity and dystonia, tremors, muscle clonus, diaphoresis, and hyperreflexia. Blood analysis showed an elevated creatine phosphokinase plasma concentration. She required continuous cardiac monitoring and treatment with intravenous fluids and diazepam, with a complete resolution of symptoms. This case highlights the importance of awareness of the adverse effects of psychotropic treatments in the pediatric population.

Objective: To compare clinical outcomes in neonates receiving empiric vancomycin or nafcillin containing regimens for neonatal late onset sepsis (nLOS).

Methods: This retrospective study evaluated neonates > 72 hours of age initiated on vancomycin/gentamicin (VANC) or nafcillin/gentamicin (NAF) for suspected nLOS. The primary composite endpoint was clinical worsening, defined as a composite of increased respiratory support or vasopressor requirement, both within the first 24 hours, or prolonged bacteremia. Secondary endpoints included acute kidney injury, methicillin-resistant Staphylococcus aureus colonization, deep-seated infection, and mortality.

Results: The final cohort included 97 neonates (46 VANC, 51 NAF). There was no difference in the clinical worsening composite (VANC 15.2% vs NAF 15.7%; p = 0.95) or in the individual components of the composite. Secondary endpoints did not yield statistically significant differences.

Conclusions: Use of nafcillin as the Gram-positive empiric treatment agent did not result in increased clinical worsening compared to vancomycin at our institution.

Thromboembolism in pediatric patients with congenital heart disease (CHD) is a commonly encountered morbidity. Feeding intolerance is also commonly encountered in patients with CHD and has a direct effect on thromboembolism treatment options, as the site of gastrointestinal absorption for each agent varies. Historically, standard anticoagulation options included unfractionated heparin, enoxaparin, or vitamin K antagonists such as warfarin. Non-vitamin K oral anticoagulants, such as rivaroxaban, have become more widely used in pediatrics since obtaining Food and Drug Administration approval, but are often considered poor options for patients receiving post-pyloric enteral feeds. Adult pharmacokinetic data suggest significant variations in volume of distribution and maximum serum concentrations based on the site of administration within the gastrointestinal tract. We report 3 patients with complex CHD and significant feeding intolerance requiring therapeutic anticoagulation who successfully received rivaroxaban through a post-pyloric feeding tube. When using therapeutic serum concentration monitoring, all 4 serum concentrations were within the reported reference range, and 3 of 4 were within the age-related geometric coefficient of variation. Rivaroxaban appears to have adequate post-pyloric absorption in pediatric patients with CHD based on serum concentration monitoring.