Optimizing Pediatric Dosing Recommendations and Treatment Management of Antiretroviral Drugs Using Therapeutic Drug Monitoring Data in Children Living With HIV

Introduction: This review summarizes the current dosing recommendations for antiretroviral (ARV) drugs in the international pediatric guidelines of the World Health Organization (WHO), US Department of Health and Human Services (DHHS), and Pediatric European Network for Treatment of AIDS (PENTA), and evaluates the research that informed these approaches. We further explore the role of data generated through therapeutic drug monitoring in optimizing the dosing of ARVs in children. Methods: A PubMed search was conducted for the literature on ARV dosing published in English. In addition, the registration documentation of European Medicines Agency and the US Food and Drug Administration for currently used ARVs and studies referenced by the WHO, DHHS, and EMA guidelines were screened. Resulting publications were screened for papers containing data on the area under the concentration–time curve, trough concentration, and peak concentration. Studies with enrolled participants with a median or mean age of ≥18 years were excluded. No restriction on publishing date was applied. Discussion and conclusion: Pediatric ARV dosing is frequently based on data obtained from small studies and is often simplified to facilitate dosing in the context of a public health approach. Pharmacokinetic parameters of pediatric ARVs are subject to high interpatient variation and this leads to a potential risk of underdosing or overdosing when drugs are used in real life. To ensure optimal use of ARVs and validate dosing recommendations for children, it is essential to monitor ARV dosing more thoroughly with larger sample sizes and to include diverse subpopulations. Therapeutic drug monitoring data generated in children, where available and affordable, have the potential to enhance our understanding of the appropriateness of simplified pediatric dosing strategies recommended using a public health approach and to uncover suboptimal dosing or other unanticipated issues postmarketing, further facilitating the ultimate goal of optimizing pediatric ARV treatment

Prioritising the most needed paediatric antiretroviral formulations: the PADO4 list

Despite considerable progress in paediatric HIV treatment and timely revision of global policies recommending the use of more effective and tolerable antiretroviral regimens, optimal antiretroviral formulations for infants, children, and adolescents remain limited. The Paediatric Antiretroviral Drug Optimization group reviews medium-term and long-term priorities for antiretroviral drug development to guide industry and other stakeholders on formulations most needed for low-income and middle-income countries. The group convened in December, 2018, to assess progress since the previous meeting and update the list of priority formulations. Issues relating to drug optimisation for neonatal prophylaxis and paediatric treatment, and those relating to the investigation of novel antiretrovirals in adolescents and pregnant and lactating women were also discussed. Continued focus on identifying, prioritising, and providing access to optimal antiretroviral formulations suitable for infants, children, and adolescents is key to ensuring that global HIV treatment targets can be met

The first combined russian experience of using perampanel in children and adolescents with epilepsy in everyday clinical practice

Background. Real world data help to provide more information on the effects and tolerability of therapy. However, data on the use of perampanel in Russian population of children remain limited. aim. To conduct a retrospective analysis of perampanel efficacy and tolerability in children and adolescents with epilepsy in real clinical practice. Materials and methods. A total of 106 children aged 4–18 years receiving perampanel as part of combination therapy for epilepsy were observed at 18 centers. Seizure frequency at 1–3, after 6 and 12 months of treatment, presence and type of adverse events (AEs) were analyzed. The main assessed efficacy parameters were seizure control, significant (≥50 %) decrease in seizure frequency. All other outcomes (<50 % decrease, no change or increased seizure frequency) were considered to be no effect. The assessed safety parameters were the percentage of patients with or without AEs and the percentage of perampanel withdrawals due to AEs. results. We defined 3 age groups for comparison: children 4–6, 7–11 and 12–17 years old. Perampanel efficacy was 69 % (seizure control – 23.6 %, ≥50 % decrease in seizure frequency – 45.3 %). The mean duration of the effect was 7.3 ± 4.1 months. No significant difference in efficacy between age groups was found. However, some greater efficacy of perampanel was noted in adolescents: absence of effect in the form of remission or significant decrease in seizures frequency was noted only in 25.5 %, with 40 % in children 4–11 years old. Among those with inefficacy, 3.8 % reported seizure aggravation. AEs occurred in only 23 % of patients, with the least frequent occurrence in adolescents (11.8 %) and the most frequent in children aged 7–11 years (40 %). The most frequent AEs was sluggishness and/or drowsiness. Discontinuation of perampanel due to AEs was required in 7.6 %. Conclusion. Perampanel has demonstrated high efficacy and good tolerability in real clinical practice among children from 4 years of age and adolescents with partial (focal) and secondary generalized seizures. The AEs that developed were not serious and very rarely led to withdrawal of the therapy. The results are comparable to those of phase III studies and previous real-world data. The usage of perampanel in children with primary generalized seizures should be further investigated. © 2022 ABV-Press Publishing House. All rights reserved.EisaiО.А. Рахманина / O.A. Rakhmanina: https://orcid.org/0000-0001-9218-2531 И.В. Волков / I.V. Volkov: https://orcid.org/0000-0002-7816-7535 О.К. Волкова / O.K. Volkova: https://orcid.org/0000-0003-3314-3895 Ю.А. Александров / Yu.A. Aleksandrov: https://orcid.org/0000-0003-3887-5219 М.В. Бархатов / M.V. Barkhatov: https://orcid.org/0000-0002-6372-4677 И.С. Бахтин / I.S. Bakhtin: https://orcid.org/0000-0003-3600-687X Г.М. Бережная / G.M. Berezhnaya: https://orcid.org/0000-0003-3917-422X А.Ю. Карась / A.Yu. Karas: https://orcid.org/0000-0001-9089-9627 Д.В. Морозов / D.V. Morozov: https://orcid.org/0000-0003-4389-9143 И.С. Бахтин / I.S. Bakhtin: https://orcid.org/0000-0003-3600-687X Т.Р. Томенко / T.R. Tomenko: https://orcid.org/0000-0002-0652-1996 Ж.М. Цоцонава / Zh.M. Tsotsonava: https://orcid.org/0000-0003-3275-5099 Конфликт интересов и финансирование. Публикация подготовлена при финансовой поддержке компании «Эйсай». Авторы несут полную ответственность за содержание статьи и редакционные решения. Conflict of interest and funding. This publication was funded by Eisai. The authors are fully responsible for the content of the article and editorial decisions

Organization of providing service to epileptologlcal patients in Tyumen city and in the South of Tyumen region

Opening of Epiieptologicai Center and interterritorial epileptological rooms will improve the quality and availability of epileptological service to the population of Tyumen and South of the Tyumen region.Открытие эпилептологического центра и межтерриториальных эпилептологических кабинетов улучшит качество и доступность оказания специализированной эпилептологической помощи населению г.Тюмени и юга Тюменской области