As we begin our 29th volume, The Journal of Pediatric Pharmacology and Therapeutics, or JPPT, will continue to serve as the primary forum advocating for optimal pharmacotherapeutics in all segments of pediatric health care—care addressing illness in the premature infant through adolescence. JPPT will remain the source for authoritative, comprehensive topic reviews, timely original research communications, brief (practice) reports, and a place for informative, abbreviated research reports and clinical vignettes. The Journal will continue to publish high-quality, informative, impactful manuscripts that move our knowledge base forward in the treatment of
Sialorrhea, defined as an excess flow of saliva or excessive secretions, is common in patients with cerebral palsy and other neurologic disorders and is associated with clinical complications such as increased risk of local skin reactions, infections, aspiration, pneumonia, and dehydration. Upon failure of non-pharmacologic measures, clinicians have several noninvasive pharmacologic options available to manage sialorrhea. This review of the literature provides detailed descriptions of medications used, efficacy, safety, and practical considerations for use of non-injectable pharmacologic agents. The literature search included published human studies in the English language in PubMed and Google Scholar from 1997 to 2022. Relevant citations within articles were also screened. A total of 15 studies representing 719 pediatric patients were included. Glycopyrrolate, atropine, scopolamine, and trihexyphenidyl all have a potential role for sialorrhea management in children; however, glycopyrrolate remains the most studied option with 374 (n = 52.0%) of the 719 patients included in the systematic review receiving this medication. Overall, glycopyrrolate showed similar efficacy but higher tolerability than its comparators in 2 comparative studies and is often considered the first-line agent. Patient-specific (age, route of administration) and medication-specific (dosage formulation, medication strength) considerations must be weighed when initiating a new therapy or switching to another medication upon treatment failure. Owing to the high propensity of adverse events with all agents, clinicians should consider initiating doses at the lower end of the dosage range, as previous studies have noted a dose-dependent relationship.
The administration of medications to children has been a challenge for parents and caregivers for generations. Pharmaceutical companies have often overcome the difficulties of weight-based dosing and the inability of most young children to swallow solid dosage forms by creating oral liquids. While oral liquids offer advantages in terms of dose flexibility, swallowability, and ease of administration for young children and patients with enteral tubes, they have been plagued by issues such as taste, volume, and texture, to name a few. While the recommendations for broader use of oral syringes can help with the issue of measuring accuracy and incremental dosing, the issues of poor taste and frequently unacceptable volumes for doses remain a problem. New oral dosage forms which have begun to enter the United States marketplace have the potential to improve adherence and acceptability of oral medications for children, but come with their own unique challenges.
Difficult analgosedation is common and challenging in the pediatric intensive care unit (PICU). It is important to study alternative and supplemental sedatives for when the first-line agents become insufficient. In this retrospective chart-review study, we report our center’s experience in using intermittent doses of enteral pentobarbital as an adjunct sedative in 13 difficult to sedate critically ill and mechanically ventilated children. We compare the average sedation score and cumulative doses of other sedatives (opioids, benzodiazepines and alpha-2 agonists) in the 24 hours before and 24 hours after enteral pentobarbital initiation. The addition of enteral pentobarbital was associated with lower State Behavioral State (SBS) scores in 8 out of the 13 patients and on average smaller doses of opioids (decreased by 11%), benzodiazepines (BZD) (decreased by 5%) and alpha-agonists (decreased by 20%). No adverse effects were noted attributable to pentobarbital administration. Enteral pentobarbital seems to be safe and effective agent in the difficult to sedate critically ill child.OBJECTIVE
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This study aims to describe the effectiveness of low initial alprostadil dosages to maintain a patent ductus arteriosus (PDA) in infants with ductal-dependent congenital heart disease (DDCHD). Secondary objectives were to describe any adverse drug events, describe prescribing trends, describe ductus arteriosus diameter changes, and compare the safety and efficacy of very low and low initial alprostadil dosage regimens. This retrospective observational cohort study at the British Columbia’s Women’s and Children’s Hospital neonatal intensive care unit and pediatric intensive care unit examined neonates admitted with DDCHD who received alprostadil to maintain ductal patency. Very low–dose alprostadil (less than 0.01 mcg/kg/min) versus low-dose alprostadil (equal to or greater than 0.01 mcg/kg/min) was examined. Effectiveness was defined as survival and infants not requiring a resuscitation event (cardiac arrest, cardiogenic shock, code blue, extracorporeal life support, requirement for emergent cardiac surgery, and respiratory acidosis). Adverse drug events with a Naranjo score of 3 or more were included. Alprostadil was effective for 88% of patients, with no difference between the very low–dose and low-dose groups. Of the 75 patients included, 25 received very low–dose alprostadil. Adverse drug events were common (51%) with neonates in the low-dose group experiencing more apnea and pyrexia than neonates in the very low–dose group. Alprostadil therapy was effective in maintaining the PDA in neonates with DDCHD with low-dosage regimens. Adverse drug events were common with both dosage regimens; however, the very low dosage appeared to have less apnea and pyrexia.OBJECTIVES
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Often we call the patient’s pharmacy to obtain a refill history to assess inhaled corticosteroid (ICS) adherence. The purpose of this project was to determine the accuracy of refill histories for ICS (with or without long-acting beta agonist) listed in Epic’s Medication Dispense History. We evaluated 61 patients and used data from 38 who met the following criteria: 1) under the care of the UF Pediatric Severe Asthma Clinic; 2) taking the same dose of the same ICS product for 6 months before the patient’s last clinic visit; and 3) having data available from the pharmacy where the last ICS prescription was electronically sent. We called the pharmacies to obtain a verbal report of their refill record. Then, we compared the number of refills reported to the number listed in Epic’s records using a Wilcoxon matched-pairs signed-ranks test. Of the 293 refill dates listed in Epic, 157 were duplicates, giving a 54% error. After deleting duplicates, the mean (SD) number of refills listed in Epic was 3.6 (2.0) compared with 3.3 (2.0) in pharmacies over a period of 6 months (p < 0.0001). After removing duplicates Epic correctly reported the total number of refills for 30 of the 38 patients (78.9%). Seven of the remaining patients had more refills listed in Epic while 1 patient had more refills dispensed. This study indicates that our version of Epic over-reports refills thus limiting assessment of adherence. In contrast, absence of refills in Epic is a clear indication of poor adherence.OBJECTIVE
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Sublingual buprenorphine has demonstrated efficacy for treatment of the neonatal opioid withdrawal syndrome (NOWS), but the current formulation used in clinical practice contains 30% ethanol. Ethanol as a pharmacologically active excipient ideally should be removed from neonatal formulations. The objective of this study was to determine the relative bioavailability of a novel ethanol-free formulation (CHF6563) compared with the commonly used ethanolic solution in a phase I, open-label, 2-period, single-dose, crossover study in healthy adults. Eighteen adult opioid-naïve volunteers were administered one of the formulations in a randomized crossover treatment. After a 10-day washout period, subjects received the other formulation. Serial blood samples were drawn for pharmacokinetic analysis over 48 hours. The geometric mean ratio (90% CIs) of the ethanol-free buprenorphine solution AUC0–last was 0.80 (0.65–0.99) and Cmax was 0.81 (0.66–0.99) compared with reference ethanolic formulation. The ethanol-free formulation had a greater degree of intersubject variability than the ethanol-containing reference formulation (coefficient of variation of 59% vs 31.5%, respectively, for AUC0–last). In an adult population, a novel ethanol-free formulation of buprenorphine containing widely used excipients demonstrated a slight decrease in bioavailability when compared with an ethanolic solution. These results will inform those seeking to develop ethanol-free pediatric drug formulations.OBJECTIVE
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Reduced bone mineral density (BMD) can negatively affect lifelong skeletal health by increasing the risk for developing osteopenia and osteoporosis. This study evaluated the relationship between BMD and cumulative doses of intravenous (IV) methotrexate (MTX) and glucocorticoids in pediatric acute lymphoblastic leukemia (ALL) survivors. The association between BMD and vitamin D concentrations measured at the time of entry into the long-term follow-up program was also assessed. This retrospective study included pediatric ALL survivors who had received a dual-energy X-ray absorptiometry (DXA) scan after the end of therapy (EOT) or within the 6 months prior to the EOT. Low/intermediate and high cumulative IV MTX doses were defined as doses less than 20,000 mg/m2 and greater than or equal to 20,000 mg/m2, respectively. Descriptive statistics, Student t test, and linear regression were used to analyze the data. A total of 62 patients, with 34 patients in the low/intermediate and 28 patients in the high cumulative IV MTX dose groups, were analyzed. The median time from EOT to DXA scan was 2.3 years. The mean DXA lumbar spine z score was significantly lower in the high cumulative IV MTX dose group compared with the low/intermediate dose group (−0.86 vs −0.14; p = 0.008). Cumulative glucocorticoid doses and vitamin D concentrations were not associated with BMD. Pediatric patients who had received cumulative IV MTX doses of greater than or equal to 20,000 mg/m2 during their ALL treatment had lower BMD than those who had received lower cumulative doses.OBJECTIVES
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In 2020, a list of Key Potentially Inappropriate Drugs in Pediatrics, known as the “KIDs List,” was published. The objective of this analysis was to evaluate institutional compliance with the recommendations in this publication and identify areas for improvement. Medications in the KIDs List were compared to the institutional formulary at a large academic medical center caring for pediatric and adult patients. Medications listed in the formulary were then evaluated for order comments and restrictions related to their use in pediatric patients. Oral liquid products and a group of commonly used intravenous (IV) medications were reviewed for potentially inappropriate excipients through available manufacturer information. The pediatric clinical specialists were then solicited to review and make recommendations for medications that had not been addressed. Of the 67 medications or classes listed in the KIDs List, 47 (70.1%) of the medications are listed in our formulary and available for use. Of these 47 medications, 4 (8.5%) included warnings related to their use in pediatric patients. Of the 270 oral liquid medications reviewed, 206 (76.3%) contained at least 1 potentially inappropriate excipient. Of the 20 commonly used IV medications, 3 (15%) contained at least 1 potentially inappropriate excipient. This review found that many medications listed in the KIDs List are included in our institution’s formulary and that few have warnings for pediatric patients built into the institutional electronic health record. Further review of medications in the formulary will be conducted to determine the next steps to implementing KIDs List recommendations.OBJECTIVES
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This study aimed to characterize medication-related practices during and immediately following rapid sequence intubation (RSI) in pediatric care units across the United States and to evaluate adverse drug events. This was a multicenter, observational study of medication practices surrounding intubation in pediatric and neonatal intensive care unit (NICU) and emergency department patients across the United States. A total of 172 patients from 13 geographically diverse institutions were included. Overall, 24%, 69%, and 50% received preinduction, induction, and neuromuscular blockade, respectively. Induction and neuromuscular blocking agent (NMBA) use was low in NICU patients (52% and 23%, respectively), whereas nearly all patients intubated outside of the NICU received both (98% and 95%, respectively). NICU patients who received RSI medications were older and weighed more. Despite infrequent use of atropine (21%), only 3 patients developed bradycardia after RSI. Of the 119 patients who received an induction agent, fentanyl (67%) and midazolam (34%) were administered most frequently. Hypotension and hypertension occurred in 23% and 24% of patients, respectively, but were not associated with a single induction agent. Etomidate use was low and not associated with development of adrenal insufficiency. Rocuronium was the most used NMBA (78%). Succinylcholine use was low (11%) and administered despite hyperkalemia in 2 patients. Postintubation sedation and analgesia were not used or inadequate based on timing of initiation in many patients who received a non-depolarizing NMBA. Medication practices surrounding pediatric RSI vary across the United States and may be influenced by patient location, age, and weight.OBJECTIVES
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This study aims to characterize the impact of a pharmacist-driven discharge medication reconciliation and counseling program targeting high-risk pediatric patients to mitigate barriers in transitions of care. This was a single-center quality improvement initiative including high-risk pediatric patients within a large academic medical center. Pharmacy, medical, and information technology team members developed a scoring system to identify patients at high risk of hospital readmission that resulted in a trigger tool built within the electronic medical record (EMR). Pharmacy workflow, the EMR documentation, and staff training were implemented. The primary end point was the number of high-risk patients with complete medication reconciliation and/or discharge counseling performed during the first 2 months after implementation. The secondary end points included quantification and qualification of the interventions conducted by a pharmacist. Pediatric clinical pharmacists conducted discharge medication reconciliation and/or counseling for 60 patients during the first 2 months after implementation. There were 65 interventions performed, including 60 discharge medication reconciliations and 5 discharge counseling sessions. Of these interventions, 22 were recommendations on appropriate medication dosing and frequency (37%), 12 on duration of therapy (20%), and 8 were medication additions (13%). There were 6 interventions on adherence assistance (10%), 6 involved selection of medication formulation (10%), 3 involved medication discontinuation (5%), 2 involved appropriate therapy selection (3%), and 1 involved medication stability (1%). All interventions were accepted and implemented by the prescribing providers. Pharmacist-driven discharge medication reconciliation and counseling programs targeting pediatric high-risk population might be an effective tool to mitigate gaps in transitions of care.OBJECTIVE
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The widespread use of highly effective cystic fibrosis transmembrane-conductance regulator modulator therapy has dramatically altered the lives of individuals with cystic fibrosis. Clinical trials leading to modulator approval by the US Food and Drug Administration demonstrated improvements in major outcome measures including pulmonary function, gastrointestinal symptoms, and quality of life. Subsequent clinical experience has confirmed significant improvement across these domains. Adverse effects reported during clinical trials included headache and dizziness amongst others including upper respiratory infections, abdominal pain, diarrhea, rash, and elevated serum transaminases. Post marketing clinical experience has suggested that there may be additional central nervous system adverse effects resulting from modulator therapy. Reported events after initiation of cystic fibrosis transmembrane-conductance regulator modulator treatment include headaches and increased prevalence of mental health concerns including anxiety and depression. We report a new tic disorder in a 7-year-old girl with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor.
Amidst the growing popularity of artificial intelligence (AI), many pharmacy students remain unaware of its potential. Alongside this unfamiliarity, undefined limitations, and blurry lines of its integration within academia create caution. Despite many concerns regarding cheating or plagiarism, AI tools may be valuable to assist in student learning. Students can navigate its potential by utilizing AI as a supplementary aid while also carefully considering its limitations. This commentary highlights the practical ways you can integrate AI into your pharmacy school educational experience, from developing study aids, idea generation, and professional communication to enhance your learning. InIntroduction
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In follow-up to our work published in the December issue of The Journal of Pediatric Pharmacology and Therapeutics,1 we used relative search interest (RSI) data for montelukast from Google Trends and data from the US Food and Drug Administration’s (FDA’s) Adverse Event Reporting System (FAERS) to determine if public interest after FDA placement of a black box warning (or “Boxed Warning”) may have influenced adverse event reporting. Because the Boxed Warning is the strongest warning by the FDA to notify patients and health care professionals of potential risk of life-threatening or significantly life-altering side effects, its