Off-Label Use of Drugs and Adverse Drug Reactions in Pediatric Units: A Prospective, Multicenter Study

Praticò, Andrea D.; Longo, Laura; Mansueto, Silvana; Gozzo, Lucia; Barberi, Ignazio; Tiralongo, Venera; Salvo, Vincenzo; Falsaperla, Raffaele; Vitaliti, Giovanna; Rosa, Mario La; Rotondò, Antonio; Avola, N; Sgarlata, D; Damiano, Annalisa; Tirantello, Massimo; Anzelmo, G; Cipolla, Domenico; Rizzo, Angelo Cascio; Russo, Antonio; Ruggieri, Martino; Salomone, Salvatore; Drago, Filippo

doi:10.2174/1574886313666180619120406

Cited by 80 publications

(84 citation statements)

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“…16 Given the potential for increasing the rate of pediatric approvals in at least part of the pediatric population at the time of adult drug approvals, the experience of the FDA with combined pediatric and adult trials is particularly valuable. The objectives of this evaluation were (1) to perform a review of the BPCA and/ or PREA and orphan drug submissions to the FDA where combined adult and pediatric trials were conducted, (2) to evaluate the most relevant therapeutic areas in which combined trials were conducted, (3) to identify the trials that reported separate safety and efficacy analyses for the pediatric subgroups, and (4) to delineate which dosing methods were most often utilized in the combined trials.…”

Section: Articlementioning

confidence: 99%

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Combined Pediatric and Adult Trials Submitted to the US Food and Drug Administration 2012–2018

Tanaudommongkon

Miyagi

Green

et al. 2020

Clin Pharma and Therapeutics

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Despite legislation incentivizing and requiring drug companies to conduct pediatric clinical trials, there still is a 9-year delay in drug approval for pediatric labeling after the initial adult drug approval. The aim of this study was to review the experience of the US Food and Drug Administration (FDA) with combined pediatric and adult trials as a means for expediting pediatric approval and labeling. Combined pediatric and adult trials submitted to the FDA from 2012 to 2018 were reviewed. Only the publicly available labels and reviews were utilized for this analysis. Combined trials were identified for 72 products, with a total of 156 combined adult and pediatric trials. The therapeutic areas with the largest number of combined trials were in pulmonology for products reviewed under the Best Pharmaceuticals for Children Act (BPCA) and/or the Pediatric Research Equity Act (PREA), and hematology reviewed under the Orphan Drug Act (ODA). All drugs that utilized combined pediatric and adult clinical trials were approved simultaneously for both the adults and that part of the pediatric population. A separate pediatric subgroup efficacy analysis was reported in 57% and 48% of products under BPCA/PREA and the ODA, respectively, with a separate safety analysis in 48% and 38% of these products. When considering both BPCA/PREA and orphan drug studies, all the combined pediatric and adult trials allowed concurrent approval and labeling for part of the pediatric population at the time of the adult approval. Medications are frequently used off-label in pediatric patients. 1 Approximately 62% to 85% of drugs prescribed for children are used off-label, 2 with higher rates for children hospitalized in neonatal and pediatric intensive care units. 3 Although off-label use does not imply improper, contraindicated, or illegal use, off-label use often lacks substantial evidence for efficacy in contrast to that required for approval. The lack of pediatric use information for approved drugs is also associated with an increased risk for adverse drug reactions. 4 Pediatric healthcare providers are then faced with the practical dilemma as to how to prescribe off-label medications for children due to a lack of reliable information.

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Section: Articlementioning

confidence: 99%

“…Additional information regarding clinical studies was also retrieved from ClinicalTrials.gov and journal publications indexed on PubMed/Medline. This study did not require Research Involving Human Subjects Committee review and approval under 45 Code of Federal Regulation (CFR) §46.101b (4).…”

Section: Data Sourcesmentioning

confidence: 99%

Combined Pediatric and Adult Trials Submitted to the US Food and Drug Administration 2012–2018

Tanaudommongkon

Miyagi

Green

et al. 2020

Clin Pharma and Therapeutics

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“…опубликовали данные о значительном увеличении риска побочных эффектов (отношение рисков 1,28; 95% доверительный интервал 0,43-3,78; p=0,002) [13]. Напротив, частота побочных реакций в большом многоцентровом проспективном исследовании педиатрических отделений составила 36,7% для «off-label use» против 63,3% для препаратов, назначаемых согласно утвержденной инструкции [14], что можно объяснить весьма взвешенным подходом врача к рекомендациям такого рода. Г.В.…”

Section: «Off-label» назначения лекарственных средств в практикеunclassified

Legal and Medical Aspects of Off-Label Medication Use. Point of View

Tsygankova

Батлук

Latyntseva

et al. 2019

Racionalʹnaâ farmakoterapiâ v kardiologii

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The current state of the Russian and foreign regulatory framework for off-label prescription of medicines is presented in the article. The existing problems of this specific drug therapy and possible solutions are described. Unfortunately, there are some gaps in the Russian legislation regarding the off-label medication use. Based on the clinical reality, in some cases, the “off-label” drugs prescription can be justified by the clinical condition of the patient, the lack of alternative approved drugs, and the availability of published scientific data that create the prerequisites for the effectiveness of this approach. When off-label drug prescribing as a forced measure, the doctor must provide a rationale for this prescription in the medical documentation, the conclusion of the consultation (with the participation of relevant specialists and the clinical pharmacologist) or the medical commission (with the participation of the administration representative), and the written informed consent of the patient or his legal representative. This information should be actively communicated to doctors in order to increase their legal literacy and prevent possible negative and legal consequences.

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“…The frequent off-label prescribing of medications in this population 2 makes them particularly vulnerable to ADRs. 3,4 Children with chronic neurologic conditions are particularly at risk of ADRs because of underlying conditions and the high frequency of polypharmacy. 2,5 The highest rate of fatalities due to antiepileptic drugs (AEDs) have been reported to occur in children.…”

Section: Introductionmentioning

confidence: 99%

Valproic Acid Induced Pancreatitis Presenting With Decreased Level of Consciousness in a Child With Tuberous Sclerosis Complex

Deschenes¹,

Autmizguine²,

Major³

et al. 2020

The Journal of Pediatric Pharmacology and Therapeutics

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A 2-year-old Caucasian boy with tuberous sclerosis complex presented to the emergency department with lethargy and new onset myoclonias. Pancreatitis, thrombocytopenia, and coagulopathy associated to a decreased level of consciousness were diagnosed. Valproic acid had been initiated 13 months before and had been slowly increased to a dose of approximately 38 mg/kg/day. All the symptoms resolved after discontinuation of the medication. The clinical presentation of this child highlights that valproic acid-related pancreatitis can present with decreased level of consciousness without associated gastrointestinal symptoms. Adverse drug reactions associated with valproic acid can lead to damage of multiple organs and may prove fatal if not promptly recognized and managed.

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Off-Label Use of Drugs and Adverse Drug Reactions in Pediatric Units: A Prospective, Multicenter Study

Cited by 80 publications

References 0 publications

Combined Pediatric and Adult Trials Submitted to the US Food and Drug Administration 2012–2018

Combined Pediatric and Adult Trials Submitted to the US Food and Drug Administration 2012–2018

Legal and Medical Aspects of Off-Label Medication Use. Point of View

Valproic Acid Induced Pancreatitis Presenting With Decreased Level of Consciousness in a Child With Tuberous Sclerosis Complex

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