Pediatric DrugsPub Date : 2024-09-01Epub Date: 2024-06-05DOI: 10.1007/s40272-024-00636-8
Lin Song, Ni Zhang, Ting-Ting Jiang, Yuntao Jia, Yao Liu
{"title":"Paediatric Drug Development in China: Current Status and Future Prospects.","authors":"Lin Song, Ni Zhang, Ting-Ting Jiang, Yuntao Jia, Yao Liu","doi":"10.1007/s40272-024-00636-8","DOIUrl":"10.1007/s40272-024-00636-8","url":null,"abstract":"<p><p>For more than two decades, regulatory agencies throughout the world released guidelines, rules and laws to stimulate and assist in paediatric drug development. In 2014, the National Health and Family Planning Commission (now known as the National Health Commission, NHC) and five other departments in China jointly issued 'Several Opinions on Safeguarding Medication for Children', after which several policies and regulations were issued to implement the priority review and approval of paediatric medicinal products and support the development of new drugs, including new dosage forms and strengths, for children. A total of 172 special medicinal products for children were approved from 2018 to 2022. Since 2016, the NHC, together with relevant administrative departments, has formulated and issued four paediatric drug lists containing 129 medicinal products to encourage research and development. At present, approximately 25 of these drugs (at exactly the same dosage forms and strengths as on the lists) have been approved for marketing, including antitumour drugs and immunomodulators, nervous system drugs, drugs for mental disorders and drugs for rare diseases. In this review, we analysed the regulations issued for promoting paediatric drug development in China, including the priority review and approval system, technical guidelines, data protection and financial support policies and general profiles of paediatric drug approval, clinical trials and the addition of information for children in the labels of marketed medicinal products. Finally, we discussed the challenges and possible strategies in the research and development of paediatric drugs in China.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Commercial Versus Compounded Preparations in Pediatric Ophthalmology.","authors":"Annegret Dahlmann-Noor, Jill Bloom, Saw Keng Lee, Samiya Chowdhury, Kanwal Nischal, Dominique Bremond-Gignac","doi":"10.1007/s40272-024-00642-w","DOIUrl":"10.1007/s40272-024-00642-w","url":null,"abstract":"<p><p>Many conditions managed by pediatric ophthalmologists are rare diseases, and even if pharmacological treatments are available, these have often not been evaluated in children. Off-label prescribing is a common practice in pediatric ophthalmology. In addition, there is often no commercial case for the production of a medicine that may only be used for a small number of patients worldwide. Compounded preparations prepared locally are therefore still in frequent use, although it is known that production may not meet stringent quality assurance standards. For several indications, commercial preparations, evaluated in rigorous clinical trials with children, are now available. Myopia management is joining the list of these indications, with low-concentration atropine formulations derived from recent clinical trials in Australia, USA, and Europe now entering the market. This short article gives an overview of the background and recent developments of compounded and commercial preparations for use in pediatric ophthalmology.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pediatric DrugsPub Date : 2024-09-01Epub Date: 2024-07-02DOI: 10.1007/s40272-024-00640-y
Elizabeth A Hall, Tracy M Hagemann, Chasity M Shelton, Hilary M Jasmin, Alexis N Calvasina, Doralina L Anghelescu
{"title":"A Narrative Review of Pain in Pediatric Oncology: The Opioid Option.","authors":"Elizabeth A Hall, Tracy M Hagemann, Chasity M Shelton, Hilary M Jasmin, Alexis N Calvasina, Doralina L Anghelescu","doi":"10.1007/s40272-024-00640-y","DOIUrl":"10.1007/s40272-024-00640-y","url":null,"abstract":"<p><p>Opioid therapy is the mainstay for managing pain in pediatric oncology. This narrative review describes the current literature regarding opioids for pediatric cancer pain. The review explores the multifaceted landscape of opioid utilization in this population, including the role of opioids in certain clinical circumstances, modalities of opioid delivery, unique opioids, outpatient and at-home pain management strategies, and other key concepts such as breakthrough pain. This review highlights the importance of individualized dosing and multimodal approaches to enhance efficacy and minimize adverse effects. Drawing from a wide range of evidence, this review offers insights to optimize pediatric oncology pain management.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pediatric DrugsPub Date : 2024-09-01Epub Date: 2024-07-04DOI: 10.1007/s40272-024-00641-x
Lisa Marie Kiesel, Astrid Bertsche, Wieland Kiess, Manuela Siekmeyer, Thilo Bertsche, Martina Patrizia Neininger
{"title":"Drug-Drug Interactions Involving High-Alert Medications that Lead to Interaction-Associated Symptoms in Pediatric Intensive Care Patients: A Retrospective Study.","authors":"Lisa Marie Kiesel, Astrid Bertsche, Wieland Kiess, Manuela Siekmeyer, Thilo Bertsche, Martina Patrizia Neininger","doi":"10.1007/s40272-024-00641-x","DOIUrl":"10.1007/s40272-024-00641-x","url":null,"abstract":"<p><strong>Background: </strong>Children treated in a pediatric intensive care unit (PICU) often receive several drugs together, among them drugs defined as high-alert medications (HAMs). Those drugs carry a high risk of causing patient harm, for example, due to a higher potential for interactions. HAMs should therefore be administered with caution, especially in a PICU.</p><p><strong>Objectives: </strong>The objective of the current study was to identify drug-drug interactions involving HAMs that increase the risk of interaction-associated symptoms in pediatric intensive care.</p><p><strong>Methods: </strong>In a retrospective study, we analyzed the electronic documentation of patients hospitalized for at least 48 h in a general PICU who received at least two different drugs within a 24-h interval. We assessed potential drug-drug interactions involving HAM on the basis of the two drug information databases UpToDate and drugs.com. Furthermore, we analyzed whether symptoms were observed after the administration of drug pairs that could lead to interaction-associated symptoms. For drug pairs involving HAM administered on at least 2% of patient days, and symptoms observed at least ten times after a respective drug pair, we calculated odds ratios, 95% confidence intervals, and p-values by using a univariate binary logistic regression.</p><p><strong>Results: </strong>Among 315 analyzed patients, 81.3% (256/315) received drugs defined as high-alert medication for pediatric patients. Those high-alert medications were involved in 20,150 potential drug-drug interactions. In 14.0% (2830/20,150) of these, one or more symptoms were observed that could be a possible consequence of the interaction, resulting in 3203 observed symptoms affecting 56.3% (144/256) of patients receiving high-alert medication. The odds ratios for symptoms observed after a drug-drug interaction were increased for eight specific symptoms (each p ≤ 0.05), especially hemodynamic alterations and disturbances of electrolyte and fluid balance. The odds ratio was highest for decreased blood pressure observed after the administration of the drug pair fentanyl and furosemide (OR 5.06; 95% confidence interval 3.5-7.4; p < 0.001). Increased odds ratios for specific symptoms observed after drug-drug interactions resulted from eight combinations composed of eight different drugs: digoxin, fentanyl, midazolam, phenobarbital, potassium salts and vancomycin (high-alert medications), and the diuretics furosemide and hydrochlorothiazide (non-high-alert medications). The resulting drug pairs were: potassium salts-furosemide, fentanyl-furosemide, vancomycin-furosemide, digoxin-furosemide, digoxin-hydrochlorothiazide, fentanyl-phenobarbital, potassium salts-hydrochlorothiazide, and midazolam-hydrochlorothiazide.</p><p><strong>Conclusions: </strong>In a cohort of PICU patients, this study identified eight specific drug pairs involving high-alert medications that may increase the risk of interaction-associa","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adverse Drug Reactions in Children with Congenital Heart Disease: A Scoping Review.","authors":"Esmaeel Toni, Haleh Ayatollahi, Reza Abbaszadeh, Alireza Fotuhi Siahpirani","doi":"10.1007/s40272-024-00644-8","DOIUrl":"10.1007/s40272-024-00644-8","url":null,"abstract":"<p><strong>Background: </strong>Congenital heart disease (CHD) is one of the leading causes of death. Safe and timely medical interventions, especially in children, can prolong their survival. The drugs prescribed for children with CHD are mainly based on the outcomes of drug therapy in adults with cardiovascular diseases, and their adverse drug reactions (ADRs) might be different. Therefore, the aim of this study was to investigate ADRs in children with CHD.</p><p><strong>Methods: </strong>This was a scoping review conducted in 2023. PubMed, Web of Science, Scopus, the Cochrane Library, Ovid, ProQuest, and Google Scholar databases were searched. All studies that reported ADRs for children with CHD and were published in English by 1 November 2023 were included in this study. Finally, the results were reported using a content analysis method.</p><p><strong>Results: </strong>A total of 87 articles were included in the study. The results showed that symptoms/signs/clinical findings, and cardiovascular disorders were the most common ADRs reported in children with CHD. The results also showed that most of the ADRs were reported for prostaglandin E1, amiodarone, prostaglandin E2, dexmedetomidine, and captopril, respectively.</p><p><strong>Conclusion: </strong>The review underscores the wide array of ADRs in children with CHD, particularly in antiarrhythmics, diuretics, beta-blockers, anticoagulants, and vasodilators, which affected cardiovascular, respiratory, endocrine, metabolic, genitourinary, gastrointestinal, and musculoskeletal systems. Tailored treatment is imperative, considering individual patient characteristics, especially in the vulnerable groups. Further research is essential for optimizing dosing, pharmacogenetics, and alternative therapies to enhance patient outcomes in CHD management.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pediatric DrugsPub Date : 2024-07-01Epub Date: 2024-05-16DOI: 10.1007/s40272-024-00633-x
Kevin Meesters, Violeta Balbas-Martinez, Karel Allegaert, Kevin J Downes, Robin Michelet
{"title":"Personalized Dosing of Medicines for Children: A Primer on Pediatric Pharmacometrics for Clinicians.","authors":"Kevin Meesters, Violeta Balbas-Martinez, Karel Allegaert, Kevin J Downes, Robin Michelet","doi":"10.1007/s40272-024-00633-x","DOIUrl":"10.1007/s40272-024-00633-x","url":null,"abstract":"<p><p>The widespread use of drugs for unapproved purposes remains common in children, primarily attributable to practical, ethical, and financial constraints associated with pediatric drug research. Pharmacometrics, the scientific discipline that involves the application of mathematical models to understand and quantify drug effects, holds promise in advancing pediatric pharmacotherapy by expediting drug development, extending applications, and personalizing dosing. In this review, we delineate the principles of pharmacometrics, and explore its clinical applications and prospects. The fundamental aspect of any pharmacometric analysis lies in the selection of appropriate methods for quantifying pharmacokinetics and pharmacodynamics. Population pharmacokinetic modeling is a data-driven method ('top-down' approach) to approximate population-level pharmacokinetic parameters, while identifying factors contributing to inter-individual variability. Model-informed precision dosing is increasingly used to leverage population pharmacokinetic models and patient data, to formulate individualized dosing recommendations. Physiologically based pharmacokinetic models integrate physicochemical drug properties with biological parameters ('bottom-up approach'), and is particularly valuable in situations with limited clinical data, such as early drug development, assessing drug-drug interactions, or adapting dosing for patients with specific comorbidities. The effective implementation of these complex models hinges on strong collaboration between clinicians and pharmacometricians, given the pivotal role of data availability. Promising advancements aimed at improving data availability encompass innovative techniques such as opportunistic sampling, minimally invasive sampling approaches, microdialysis, and in vitro investigations. Additionally, ongoing research efforts to enhance measurement instruments for evaluating pharmacodynamics responses, including biomarkers and clinical scoring systems, are expected to significantly bolster our capacity to understand drug effects in children.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pediatric DrugsPub Date : 2024-07-01Epub Date: 2024-06-14DOI: 10.1007/s40272-024-00639-5
Sana Younus, Lauren Havel, Jordan T Stiede, Catherine E Rast, Kirti Saxena, Wayne K Goodman, Eric A Storch
{"title":"Pediatric Treatment-Resistant Obsessive Compulsive Disorder: Treatment Options and Challenges.","authors":"Sana Younus, Lauren Havel, Jordan T Stiede, Catherine E Rast, Kirti Saxena, Wayne K Goodman, Eric A Storch","doi":"10.1007/s40272-024-00639-5","DOIUrl":"10.1007/s40272-024-00639-5","url":null,"abstract":"<p><p>Pediatric obsessive-compulsive disorder (OCD) is a chronic, potentially debilitating psychiatric condition. Although effective treatments exist, at least 10% of youth do not achieve remission despite receiving first-line treatments. This article reviews the extant, albeit limited, evidence supporting treatment approaches for youth with treatment-resistant OCD. A literature search for articles addressing pediatric treatment-resistant OCD was conducted through April 11, 2024. These results were augmented by searching for treatment-resistant OCD in adults; treatment strategies discovered for the adult population were then searched in the context of children and adolescents. In general, intensive treatment programs and antipsychotic augmentation of an antidepressant had the most substantial and consistent evidence base for treatment-resistant youth with OCD, although studies were limited and of relatively poor methodological quality (i.e., open trials, naturalistic studies). Several pharmacological approaches (clomipramine, antipsychotics [e.g., aripiprazole, risperidone], riluzole, ketamine, D-cycloserine, memantine, topiramate, N-acetylcysteine, ondansetron), largely based on supporting data among adults, have received varying levels of investigation and support. There is nascent support for how to treat pediatric treatment-resistant OCD. Future treatment studies need to consider how to manage the significant minority of youth who fail to benefit from first-line treatment approaches.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pediatric DrugsPub Date : 2024-07-01Epub Date: 2024-05-21DOI: 10.1007/s40272-024-00628-8
Chance S Friesen, Valentina Shakhnovich, Paul Toren, Brandon Retke, Jennifer Schurman, Jennifer Colombo, Amanda Deacy, Craig A Friesen, Susan Abdel-Rahman
{"title":"A Pilot Study of Ketotifen in Patients Aged 8-17 Years with Functional Dyspepsia Associated with Mucosal Eosinophilia.","authors":"Chance S Friesen, Valentina Shakhnovich, Paul Toren, Brandon Retke, Jennifer Schurman, Jennifer Colombo, Amanda Deacy, Craig A Friesen, Susan Abdel-Rahman","doi":"10.1007/s40272-024-00628-8","DOIUrl":"10.1007/s40272-024-00628-8","url":null,"abstract":"<p><strong>Background and objective: </strong>Mast cells have been implicated in abdominal pain-associated disorders of gut-brain interaction, such as functional dyspepsia. As such, ketotifen, a second-generation antihistamine and mast cell stabilizer, could represent a viable treatment option in these conditions. The primary aim of the current pilot study was to assess clinical response to ketotifen and assess pharmacokinetics in youth with functional dyspepsia.</p><p><strong>Methods: </strong>We conducted a pilot randomized, double-blind, placebo-controlled, cross-over trial of ketotifen in 11 youth with functional dyspepsia and duodenal mucosal eosinophilia with 4 weeks of active treatment at a dose of 1 mg twice daily. Global clinical response was graded on a 5-point Likert Scale. A single plasma sample was obtained at steady state for pharmacokinetic analysis.</p><p><strong>Results: </strong>Ketotifen was not superior to placebo with regard to global clinical response. Only 18% of patients demonstrated a complete or near-complete clinical response. The estimated half-life was 3.3 h.</p><p><strong>Conclusions: </strong>While ketotifen was not superior to placebo, this study highlights several important challenges for developing drug trials for youth with chronic abdominal pain. Recommendations are made for designing a larger treatment trial for ketotifen in this patient group.</p><p><strong>Clinical trial registration: </strong>This study was registered at ClinicalTrials.gov: NCT02484248.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pediatric DrugsPub Date : 2024-07-01Epub Date: 2024-06-16DOI: 10.1007/s40272-024-00638-6
Bo-Hao Tang, Qiu-Yue Li, Hui-Xin Liu, Yi Zheng, Yue-E Wu, John van den Anker, Guo-Xiang Hao, Wei Zhao
{"title":"Machine Learning: A Potential Therapeutic Tool to Facilitate Neonatal Therapeutic Decision Making.","authors":"Bo-Hao Tang, Qiu-Yue Li, Hui-Xin Liu, Yi Zheng, Yue-E Wu, John van den Anker, Guo-Xiang Hao, Wei Zhao","doi":"10.1007/s40272-024-00638-6","DOIUrl":"10.1007/s40272-024-00638-6","url":null,"abstract":"<p><p>Bacterial infection is one of the major causes of neonatal morbidity and mortality worldwide. Finding rapid and reliable methods for early recognition and diagnosis of bacterial infections and early individualization of antibacterial drug administration are essential to eradicate these infections and prevent serious complications. However, this is often difficult to perform due to non-specific clinical presentations, low accuracy of current diagnostic methods, and limited knowledge of neonatal pharmacokinetics. Although neonatal medicine has been relatively late to embrace the benefits of machine learning (ML), there have been some initial applications of ML for the early prediction of neonatal sepsis and individualization of antibiotics. This article provides a brief introduction to ML and discusses the current state of the art in diagnosing and treating neonatal bacterial infections, gaps, potential uses of ML, and future directions to address the limitations of current studies. Neonatal bacterial infections involve a combination of physiologic development, disease expression, and treatment response outcomes. To address this complex relationship, future models could consider appropriate ML algorithms to capture time series features while integrating influences from the host, microbes, and drugs to optimize antimicrobial drug use in neonates. All models require prospective clinical trials to validate their clinical utility before clinical use.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pediatric DrugsPub Date : 2024-07-01Epub Date: 2024-05-23DOI: 10.1007/s40272-024-00634-w
Sohita Dhillon
{"title":"Inotuzumab Ozogamicin: First Pediatric Approval.","authors":"Sohita Dhillon","doi":"10.1007/s40272-024-00634-w","DOIUrl":"10.1007/s40272-024-00634-w","url":null,"abstract":"<p><p>Inotuzumab ozogamicin (BESPONSA™) is a CD22-targeted monoclonal antibody drug conjugate (ADC) developed by Pfizer for the treatment of CD22-postive B-cell precursor acute lymphoblastic leukaemia (ALL). Inotuzumab ozogamicin comprises a humanized IgG4 anti-CD22 monoclonal antibody covalently linked to the potent DNA-binding cytotoxic agent N-acetyl-gamma-calicheamicin dimethylhydrazide (CalichDMH) via a linker. Inotuzumab ozogamicin binds to CD22-expressing tumour cells, facilitating the delivery of conjugated CalichDMH, which after intracellular activation induces double strand DNA breaks, ultimately leading to cell cycle arrest and apoptotic cell death. Inotuzumab ozogamicin is approved in the USA, Europe and several countries worldwide for the treatment of relapsed or refractory CD22-positive B-cell precursor ALL in adults. On 6 March 2024, inotuzumab ozogamicin received its first pediatric approval in the USA for this indication in patients aged ≥ 1 years. Inotuzumab ozogamicin has since been approved in Japan in March 2024 for the same indication in pediatric patients. This article summarizes the milestones in the development of inotuzumab ozogamicin leading to this first approval for the treatment of relapsed or refractory CD22-positive B-cell precursor ALL in pediatric patients.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}