Drugs In Pediatric Patients Research Articles

Etiology and Medication of Hospitalized Children With Hypertension: A Retrospective Study.

With the increasing incidence of hypertension in children, the lack of high-quality research data on antihypertensive drugs in pediatric patients restricts treatment options for clinicians and can lead to suboptimal outcomes. We conducted a retrospective analysis of clinical data from hospitalized pediatric patients diagnosed with hypertension and treated with antihypertensive drugs in the past 3years. The study included 203 pediatric patients (119 males and 84 females), with an average age of 8.9±4.7years (range: 0.1-17years). Clinical symptoms of hypertension were observed in 132 participants (65.0%), and the conditions in all cases were classified as primary or secondary hypertension. Renal causes (71 patients, 35.0%) and drug-induced factors (39 patients, 19.2%) were the main causes of secondary hypertension. Nifedipine (137 patients, 67.5%) was the most commonly prescribed medication, followed by captopril (84 patients, 41.4%). Multiple antihypertensive medications were prescribed to 99 participants (48.8%), and blood pressure returned to normal in 111 patients (54.7%). Hypertension-related organ damage was observed in 47 patients (23.2%). Timely diagnosis and treatment of hypertension are critical to prevent organ damage in pediatric patients. Although nifedipine was widely used in this pediatric cohort, the appropriateness of this treatment remains unclear. Emphasis should be placed on monitoring target organs affected by pediatric hypertension, and post-discharge antihypertensive treatment should include thorough follow-ups and documentation.

Age-Specific ADME Gene Expression in Infant Intestinal Enteroids.

In childhood, developmental changes and environmental interactions highly affect orally dosed drug disposition across the age range. To optimize dosing regimens and ensure safe use of drugs in pediatric patients, understanding this age-dependent biology is necessary. In this proof-of-concept study, we aimed to culture age-specific enteroids from infant tissue which represent its original donor material, specifically for drug transport and metabolism. Enteroid lines from fresh infant tissues (n = 8, age range: 0.3-45 postnatal weeks) and adult tissues (n = 3) were established and expanded to 3D self-organizing enteroids. The gene expression of drug transporters P-gp (ABCB1), BCRP (ABCG2), MRP2 (ABCC2), and PEPT1 (SLC15A1) and drug metabolizing enzymes CYP3A4, CYP2C18, and UGT1A1 was determined with RT-qPCR in fresh tissue and its derivative differentiated enteroids. Expression levels of P-gp, BCRP, MRP2, and CYP3A4 were similar between tissues and enteroids. PEPT1 and CYP2C18 expression was lower in enteroids compared to that in the tissue. The expression of UGT1A1 in the tissue was lower than that in enteroids. The gene expression did not change with the enteroid passage number for all genes studied. Similar maturational patterns in tissues and enteroids were visually observed for P-gp, PEPT1, MRP2, CYP3A4, CYP2C18, and VIL1. In this explorative study, interpatient variability was high, likely due to the diverse patient characteristics of the sampled population (e.g., disease, age, and treatment). To summarize, maturational patterns of clinically relevant ADME genes in tissue were maintained in enteroids. These findings are an important step toward the potential use of pediatric enteroids in pediatric drug development, which in the future may lead to improved pediatric safety predictions during drug development. We reason that such an approach can contribute to a potential age-specific platform to study and predict drug exposure and intestinal safety in pediatrics.

Hypercalcemia in children induced by denosumab: a case report and an analysis of the FDA adverse event reporting system database

ABSTRACT Background The potential risks of denosumab on pediatric patients have raised concerns about its safety. This article aims to analyze the adverse effects of denosumab in minors, with a specific focus on hypercalcemia. Research design and methods A case study involving a child was analyzed. The OpenVigil 2.1 was utilized to extract adverse event data from the FAERS database, focusing on denosumab as the primary suspect drug in pediatric patients. The study also reviewed published cases of children developing hypercalcemia after discontinuing denosumab. Results The incidence of denosumab induced hypercalcemia in individuals under 18 years old is significantly higher than the overall incidence. The signal value for hypercalcemia was higher in the male group and was highest in the adolescent group. Hypercalcemia usually appeared approximately 4 months after denosumab discontinuation. Males had a higher peak blood calcium level. Patients aged 0–11 years had a higher average peak serum calcium compared to aged 12–17 years. Conclusions This study highlights the risk of hypercalcemia after discontinuation of denosumab in minors, with young age and male gender identified as potential high-risk factors. These findings offer valuable safety warnings and preventative measures for the secure administration of this drug in pediatric populations.

Pattern of Adverse Drug Reactions in Extremes of Age Group Reported to a Tertiary Care Hospital

ABSTRACT Background: The World Health Organization (WHO), defined adverse drug reactions (ADRs) as “any noxious and unintended response to a drug, which occurs at doses normally used in humans for prophylaxis, diagnosis and treatment of the disease or for the modification of physiological functions.” Pediatrics (≤12 years) and geriatrics (≥65 years) are the extreme age groups that are more vulnerable for ADRs. Aim and Objectives: To determine ADRs time-plausible relationship, clinical spectrum, causality, and severity in extreme age group patients. Materials and Methods: All the ADRs reported to ADR monitoring center among geriatrics and pediatrics patients after Institutional Ethics Committee approval were collected from January 2015 to July 2022. The collected reports were analyzed for ADR pattern, drug groups, Causality (as per WHO-Uppsala Monitoring Centre scale) and severity (Modified Hartwig scale). Results: Out of 4705 ADRs, 176 (3.74%) were reported in geriatric and 181 (3.84%) in pediatric patients. In geriatric patients, anti-neoplastic drugs followed by cardiovascular drugs were the most commonly implicated drugs, erythematous rash and dyspnea were the most common ADRs. Erythematous rash and diarrhea were the most commonly ADRs and immunological agents followed by antimicrobials were implicated drugs in pediatric patients. In geriatric patients 84.1% were mild, 14.8% moderate, and 1.1% severe reactions whereas in pediatric group 91.2% were mild, 8.3% moderate, and 0.5% severe ADRs. Two cases of toxic epidermal necrolysis and one case of Steven–Johnson syndrome were reported in geriatric and pediatric patients respectively. Causality assessment of the majority of ADRs in geriatric age group was possible (79.5%) and in pediatric age group it was probable (61.3%). Conclusion: Extreme age group populations are more vulnerable to ADRs due to comorbidities, polypharmacy and drug interactions in elderly people and immature hepatobiliary and renal systems in pediatric age. Hence, active surveillance of drugs and education of prescribers will help to minimize the risk of ADRs in this susceptible population.

A rare variant of the development of the proarrhythmogenic effect of etacizine in a child with chronic kidney disease (clinical case)

This article describes a rare clinical case of the development of severe ventricular tachycardia while taking etacizine in a 3-year-8-month-old patient with chronic kidney disease. A clinical case demonstrates the pharmacodynamics and pharmacokinetics of class 1C antiarrhythmic drugs in pediatric patients with kidney pathology.

Response to Dabrafenib and Tramatenib in an Extra-Cranial Avm with BRAF V600E Mutation

Background: Arteriovenous malformations (AVMs) are blood vessel malformations characterized by shunting of blood through dilated veins and arteries. KRAS is an effector molecule in a MAPK pathway that mediates activation of downstream processes such as BRAF production related to known proliferative disorders such as AVMs. Similarly MAP2K1 mutations that encodes for MEK have recently been implicated in sporadic intracranial and extracranial AVMs. Inhibition of the RAS/MAPK pathway is of interest in treatment of vascular malformations. Objective: We report a case of treatment response of a BRAF mutated arteriovenous malformation with MEK and RAF inhibitors. Description of the case: A 22 year old male presented initially at 6 years of age with swelling of the left face involving the cheek and mandible area, the area continued to grow in size with associated pain and rarely intermittent bleeding from the left buccal mucosa. US and MRI showed evidence of an AVM. He underwent 2 embolizations followed by debulking with some improvement of the swelling. Pathology revealed a BRAF V600 mutation by molecular testing. He was treated with oral Dafrafenib 150 mg twice daily and Trametinib 2 mg daily, showing improvement of the swelling with a 3 month old follow up. Conclusion: AVMs continue to present treatment challenges for hematologists, surgeons and other care providers. Treatment with target directed therapies with inhibitors of the RAS-RAF-MEK-ERK pathway such as Trametinib and Dafrafenib have the potential to make a positive impact in the current management of these entities. Further studies are required to explore safety and impact of long term effects of these drugs in pediatric patients.

Personalized application of antimicrobial drugs in pediatric patients with augmented renal clearance: a review of literature.

ARC impacts antimicrobial drugs in pediatric patients. • ARC is inextricably linked to the failure of antimicrobial therapy, recurrence of infection, and subtherapeutic concentrations of drugs. • This study provides an updated overview of the influence of ARC on medication use and clinical outcomes in pediatric patients. • In this context, there are several recommendations for using antibiotics in pediatric patients with ARC: 1) increase the dose administered; 2) prolonged or continuous infusion administration; 3) use of TDM; and 4) use alternative drugs that do not undergo renal elimination.

Drug utilization study of antiepileptic drugs in the pediatric department in a tertiary care hospital

Background: Epilepsy is basically any disorder characterised by uncontrolled excessive and synchronous electrical discharges in various brain areas resulting in spontaneously recurrent seizures which typically last from seconds to minutes. For the rationale drug use and to suggest measures to change prescribing habits for the better management of epileptic seizures it is very necessary to know the prescription pattern of these drugs. This study aims to study the utilisation pattern of antiepileptic drugs in paediatric patients in a tertiary care hospital. Methods: The present retrospective observational study was conducted at Daya Hospital, Thrissur. Ninety six Paediatric patients of either gender diagnosed to had epilepsy and taking treatment from Daya Hospital were included in the study. Patient’s detailed medical history, demographic details and other required information was recorded. Results: The study showed that out of 96 patients typical febrile seizure (73%) was found to be the most common form of seizure among paediatric patients of age group 1- 5 years of age. Clobazam was the most commonly prescribed (71%) AED followed by midazolam (69%). 27% patients were prescribed monotherapy. Clobazam + Midazolam was the most commonly (31%) used combination. Conclusion: From this study it was found that majority of prescription was without a generic name. It was concluded that Clobazam was the highly prescribed drug followed by Midazolam. There was no any serious drug drug interactions. There is a need for further up-to-date studies to determine the drug utilisation pattern of paediatric patients.

Clinical use of gastric antisecretory drugs in pediatric patients with gastroesophageal reflux disease: a narrative review.

Gastroesophageal reflux (GER) is a common condition in infants. Usually, it resolves spontaneously in 95% of cases within 12-14 months of age, but gastroesophageal reflux disease (GERD) may develop in some children. Most authors do not recommend pharmacological treatment of GER, while the management of GERD is debated. The aim of this narrative review is to analyze and summarize the available literature on the clinical use of gastric antisecretory drugs in pediatric patients with GERD. References were identified through MEDLINE, PubMed, and EMBASE search engines. Only articles in English were considered. The following keywords were used: "gastric antisecretory drugs", "H2RA", "PPI", "ranitidine", "GERD", "infant", "child". Increasing evidence of poor efficacy and potential risks of proton pump inhibitors (PPIs) is emerging in neonates and infants. Histamine-2 receptor antagonists (H2RAs), including ranitidine, have been used successfully in older children, although less effective than PPIs at relieving symptoms and healing GERD. However, in April 2020, both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) requested manufacturers of ranitidine to remove all ranitidine products from the market due to the risk of carcinogenicity. Pediatric studies comparing effectiveness and safety of different acid-suppressing treatments for GERD are generally inconclusive. A proper differential diagnosis between GER and GERD is crucial to avoid the overuse of acid-suppressing medications in children. Further research should be directed towards the development of novel antisecretory drugs, with proven efficacy and good safety profile, for treating pediatric GERD, particularly in newborns and infants.

Comparison of dexmedetomidine alone or with other sedatives for paediatric sedation during magnetic resonance imaging: a systematic review.

Aim To compare the outcome of sole dexmedetomidine or with other sedative drugs in paediatric patients during magnetic resonance imaging (MRI). Methods Literature was obtained from PubMed and ScienceDirect from 2010-2020 using key words: sedation, paediatric, dexmedetomidine, ambulatory, MRI, ketamine, propofol, midazolam. The literature selection was based on Participant, Intervention, Comparators, Outcomes (PICO) analysis. All English full-text and peer-reviewed articles were included. The primary outcome was hemodynamic stability, respiratory compromise, and recovery time. The risk of bias analysis was assessed using Cochrane collaboration Risk of Bias (RoB 2.0). Result Of 106 studies, 17 studies were included with a total 3.430 paediatric patients undergoing MRI. Dexmedetomidine alone provides a more stable hemodynamic but longer recovery time than ketamine, propofol or midazolam. The combination of dexmedetomidine and ketamine provides more stable hemodynamics, especially in the incidence of hypotension and bradycardia, and does not significantly reduce airway configuration more than sole dexmedetomidine or ketamine. Intranasal dexmedetomidine is more recommended than its combination with midazolam. Combining dexmedetomidine with ketamine, propofol or midazolam provides a shorter recovery time. Conclusion A combination of dexmedetomidine with other sedatives such as ketamine, propofol and midazolam is better than sole dexmedetomidine for paediatric sedation during magnetic resonance imaging.

Treatment strategy for children and adolescents with type 2 diabetes-based on ISPAD Clinical Practice Consensus Guidelines 2022.

The principles of treatment for children and adolescents with type 2 diabetes include dietary and exercise management. For dietary management, a relatively modest dietary regimen with an appropriate energy source composition is recommended. Moderate- to vigorous-intensity aerobic activity is recommended for at least 60 min/d. Family members are encouraged to modify their lifestyles. Some patients fail to improve hyperglycemia through dietary and exercise management and eventually require pharmacological treatment. If the patient is metabolically stable (HbA1c level < 8.5% [69 mmol/mol]), metformin is the first-line treatment of first choice. In a case with ketosis or HbA1c of more than 8.5% (69 mmol/mol), insulin will be required initially with once daily basal insulin (0.25-0.5 units/kg). The goal of the initial treatment is to attain an HbA1c level < 7.0% (53 mmol/mol). If the glycemic goal is not attained, the addition of a second agent should be considered. However, the use of antihyperglycemic drugs in pediatric patients is limited in most countries. Therefore, the efficacy and safety of these drugs used in adult patients, including GLP-1 receptor agonists and SGLT2 inhibitors, should be evaluated in pediatric patients worldwide.

Graves' Disease in Children: An Update.

Graves' disease (GD) is the most common cause of hyperthyroidism in children. A common GD symptom is a goiter. The usual biochemical profile in children with GD is a decreased thyroid hormone stimulating hormone (TSH) level and high free thyroxine (FT4) and free triiodothyronine (FT3) concentrations. The presence of thyroid receptor antibodies (TRAb) is the most important specific immunological sign for diagnosing GD. The treatment choices for pediatric GD are anti-thyroid drugs (ATDs), radioiodine, and thyroidectomy, but the risks and benefits of each modality are different. Management recommendations include the first-line use of a prolonged course of ATDs for at least 3 years and potentially 5 years or more. Rituximab and Teprotumumab are new novel alternative medications for the treatment of adult patients with GD and Graves' orbitopathy respectively, but evidence of the efficacy and safety of these drugs in pediatric patients with GD is lacking.

Improving Drug Therapy for Pediatric Patients: Unfinished History of Pediatric Drug Development.

Improving Drug Therapy for Pediatric Patients: Unfinished History of Pediatric Drug Development.

Safety of Anti-Angiogenic Drugs in Pediatric Patients with Solid Tumors: A Systematic Review and Meta-Analysis.

Cancer is a clinical condition that can benefit from anti-angiogenic drugs (AADs). Given the low prevalence and the heterogeneity of childhood cancers, information about the safety of these drugs in pediatric patients is partially assessed. The aim of this study was to evaluate the safety of AADs in pediatric patients with solid tumors. Clinical trials and observational studies were searched in PubMed, ISI Web of Science, and ClinicalTrials database For each included study, adverse events (AEs) were extracted. A meta-analysis was conducted by pooling proportions of AEs using a random intercept logistic regression model. Seventy studies were retrieved. Most part were clinical trials (55 out of 70), and only fifteen observational studies were found. Overall, proportion of serious and non-serious AEs of AADs used as monotherapy was 46% and 89%, respectively. Proportions of serious AEs varied among drugs: sunitinib, 79%; lenvatinib, 64%; sorafenib, 48%; ramucirumab, 41%; pazopanib, 30%; and vandetanib, 27%. A higher proportion of non-serious hematological AEs was found in the patients receiving pazopanib with respect to sunitinib and lenvatinib. The safety profile of AADs has been extensively investigated for mostly drugs in phase I and II trials and is limited to acute toxicities. Overall, one out of two patients using AAD drugs in monotherapy experienced a serious AE despite proportions varied per single drugs. When AADs were combined with standard chemotherapy, the proportion of AEs varied in relation to the single combinations.

Pharmacoeconomics Aspects of Antiepileptic Drugs in Pediatric Patients with Epilepsy

Objective: This study assessed the differentiation of treatment costs with newer and older antiepileptic drugs (AEDs) through its correlation with treatment effectiveness and an adverse event (AE) in pediatric patients with epilepsy (PPE). Methods: PPE on monotherapy of AEDs for the last 6 months were screened for this study. Seizure frequency during the study was compared with that within 6 months before the study. The following parameters were also assessed: quality of life in epilepsy, Pittsburgh Sleep Quality Index, and Liverpool AEs Profile. An incremental cost-effectiveness ratio (ICER) analysis based on the costs of pharmacotherapy was also performed. Results: Out of 80 PPE, 67 completed the study, and 13 PPE were lost after failing to meet the inclusion criteria. A total of 56.71% of PPE were on newer AEDs, and 43.28% were on older AEDs. Newer and older AEDs did not differ significantly in seizure frequency reduction and quality of life parameters, although these were improved significantly during the study period. As per ICER, newer AEDs need an additional EUR 36.82 per unit reduction in seizure frequency. Conclusion: Newer AEDs have comparatively better efficacy, although not significantly better than older AEDs. However, the additional cost per unit improvement is quite high with newer AEDs, necessitating pharmacoeconomic consideration in pediatric epilepsy treatment.

Safety and tolerability of antipsychotic drugs in pediatric patients

Safety and tolerability of antipsychotic drugs in pediatric patients

EVALUATION OF USE OF DIARRHEA DRUG IN PEDIATRIC PATIENTS AT DOLAT RAYAT HEALTH CENTER KARO DISTRICT

Diarrhea is a condition in which there is an imbalance in absorption, secretion of water and electrolytes, resulting in a frequency disorder of defecation more than 3 times a day with liquid or semi-solid stools, with or without mucus or blood. Diarrheal disease is still a global problem with a high degree of morbidity and mortality in various countries, especially in developing countries, and is one of the main causes of high child morbidity and mortality in the world. This study aims to determine the profile and rationality of using diarrhea drugs in pediatric patients at the Dolat Rayat Health Center, Karo Regency. This research was conducted using a retrospective descriptive method. The results of the study from the Dolat Rayat Health Center in Karo Regency showed that of the 235 patients who suffered from diarrhea the most were men (63-83%) and at the age of 2 years old infants (48.51%) with an average per patient of 1.28 drug items. The most widely used type of diarrhea drug was zinc (62.67%) in the form of syrup (54.67%). The rationality for using diarrhea medicines based on the 2011 Indonesian Ministry of Health guidelines includes the criteria for right indication (100%), right drug (100%), right patient (99.15%), and right dose (96.17%). Most of the use of diarrhea drugs in pediatric patients at the Dolat Rayat Health Center in Karo Regency is rational.

Current situation of pediatric clinical trials in China: focus on trials for drug marketing application and administrative approval

BackgroundResearch and development of pediatric drug faces many difficulties and pediatric clinical trials remain a challenge. Since 2011, a series of measures have been taken to encourage research, development of drugs for pediatric patients in China. In this study, we analyzed pediatric clinical trials conducted in China to provide reference for research and development of pediatric drugs and formulation of relevant policies.MethodsWe conducted a cross-sectional observational study of pediatric trials registered in the Drug Trial Registration and Information Publication Platform before Oct. 31, 2021. All trials that recruited children (under 18 years old as defined in China) were retrieved and general characteristics of the trials and the research drugs were extracted and analyzed. The data were extracted and statistically analyzed by excel 2010 and SPSS 22.0, respectively.ResultsThere were 588 registered pediatric clinical trials, which accounted for 3.94% of the total registered trials. The overall average annual growth rate of the number of trials from 2013 to 2020 was 14.47% (P < 0.01). Of the 588 trials included, there were 312 trials (53.06%) with only children as subjects, 127 trials (21.60%) with research drugs only for children use, and the median of target subject number was 320 with the range of 8 to 600,000. The sponsors and the principal investigators were mainly located in the eastern and northern China. 325 trials were vaccine trials, and the dosage form was mainly injection. There were 98 non-vaccine biological product trials (mainly injections), 135 chemical compound drug trials (mainly tablets), 30 traditional Chinese medicine/natural drugs (mainly granules). Indications of the non-vaccine drugs were mainly diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism.ConclusionThe number of pediatric clinical trials in China has increased these years. To further promote pediatric clinical trials and motivate pediatric appropriate drug marketing application and administrative approval, conducting large pediatric clinical trials, further development of dosage forms suitable for children with special attention to neonates and prematurity, and improving uneven geographical distribution of sponsors and researchers are the current challenges.

Off-label use of psychotropic drugs in a Swiss paediatric service: similar results from two different cohort studies.

The high off-label use of drugs in paediatric patients raises questions on the efficacy and safety when prescribing psychotropic drugs. In our studies, we aimed to characterise the use of psychotropic drugs in the paediatric service of a tertiary hospital and quantify the proportion of off-label prescriptions with respect to age, indication and dosage recommendations approved in Switzerland, France and the USA. We conducted a retrospective cohort study (RCS) that included hospitalised patients from 1 December 2017, to 28 June 2018 with at least one PD prescription (n = 74) and a prospective cohort study (PCS) that included those hospitalised from 29 June 2018, to 30 November 2018 with at least one psychotropic drug prescription (n = 37). For both studies, we collected demographic, medical and medication data. Off-label prescriptions were identified by comparing the marketing authorisations published in the three selected countries. The average age of RCS and PCS patients were 13 ± 3 years and 14 ± 2 years, respectively. Of the 168 and 86 psychotropic prescriptions collected in the RCS and PCS, respectively, 70% and 71% prescriptions were off-label based on Swiss marketing authorisations. These rates declined when compared with French marketing authorisations (61% and 67% prescriptions) and were significantly lower when compared with American marketing authorisations (56% and 51% prescriptions). Psychotropic drugs were often prescribed as needed in both studies (53% and 43% of prescriptions), with only half of the patients actually receiving one of these prescribed psychotropic drugs. Our results showed a high proportion of off-label prescriptions of psychotropic drugs in a hospital setting. The off-label prescription rates according to Swiss marketing authorisations were the highest when compared with French and American marketing authorisations. Harmonisation of either international marketing authorisations or dosage recommendations at a national level could be a step forward to improved and evidence-based use of psychotropic drugs in children and adolescents.

Ontogeny of Pediatric Pharmacogenetics: Celebrating the Past and Vision for the Future.

Ontogeny of Pediatric Pharmacogenetics: Celebrating the Past and Vision for the Future.