Use of off-label and unlicenced drugs in hospitalised paediatric patients: a systematic review

Magalhães, José Pedro; Rodrigues, António Teixeira; Roque, Fátima; Figueiras, Adolfo; Falcão, Amı́lcar; Herdeiro, María Teresa

doi:10.1007/s00228-014-1768-9

Cited by 99 publications

(85 citation statements)

References 66 publications

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“…In our study, the primary reasons for off-labeled/unlicensed prescriptions were age and indications, which was a similar finding of a previous systematic review 12. On the other hand, other studies reported that the route of administration was the most common reason for off-labeled/unlicensed prescriptions,713 for example, buccal administration of sedatives and analgesics, and administration of drugs via enteral feeding tube.…”

Section: Discussionsupporting

confidence: 89%

Safety and Efficacy of Off-label and Unlicensed Medicines in Children

et al. 2018

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BackgroundThe aim of this study was to explore the use of off-label/unlicensed drugs to confirm the safety and efficacy of their prescription in children in Korea.MethodsIn this retrospective study, we analyzed data of patients who received any of the 32 drugs between January–December 2014 in tertiary hospitals in Korea, including demographics, diagnoses, reasons for the medication, administration route, and details of adverse drug reactions. Additionally, the mortality in the cohort was assessed. The primary outcomes were efficacy and safety, including mortality, of these drugs in pediatric patients. The secondary outcomes were the current statuses of the use of off-label/unlicensed drugs in two centers.ResultsTotally, 5,130 prescriptions were found in 2,779 patients. Age (73.5%) and indication (11.7%) were the most frequent reasons for prescriptions being off-labeled/unlicensed. Approximately 88% of the prescriptions were effective, and 19% of the patients developed adverse drug reactions. The number of prescriptions was significantly higher in children with adverse drug reactions than it was in those without (2.8 vs. 1.5; P < 0.001). The number of prescribed off-label/unlicensed medicines and age at prescription were independently associated with adverse drug events (odds ratio, 1.55 and 1.1; P < 0.001 and 0.034, respectively).ConclusionChildren are still prescribed medicines that are not authorized in terms of age, weight, indications, or routes of administration. Therefore, many old products require re-assessment of authorization. More prospective clinical studies should be performed to confirm the efficacy and safety of drugs in the pediatric population.

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Section: Discussionsupporting

confidence: 89%

Safety and Efficacy of Off-label and Unlicensed Medicines in Children

et al. 2018

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mentioning

confidence: 58%

“…In a recent meta-analysis (2015) evaluating 829 (1994-2012) studies on prescribing practices in pediatric hospital care, off-label and unlicensed medicines prescriptions ranged from 12 to 71 % and 0.2 to 48 %. These authors hereby reconfirmed that (pre)term neonates were still most commonly exposed to off-label and unlicensed medicines [12].The federal US legislation and similar European initiatives have resulted in a relevant increase in pharmacological studies in children, with a subsequent significant increase in label changes. Unfortunately, too few included drug label changes specific to neonates.…”

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confidence: 71%

Neonates and medicines: a roadmap to further improve neonatal pharmaceutical care

Allegaert

Sherwin

2016

Eur J Pediatr

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The treatment of newborns with safe and effective medicines is of critical importance for their outcome and subsequent quality of life. Despite this, it is still a common practice to prescribe medicines to neonates outside the label, extrapolating from dosing regimens and indications validated in older populations and based on non-neonatal pathophysiology. In a recent meta-analysis (2015) evaluating 829 (1994-2012) studies on prescribing practices in pediatric hospital care, off-label and unlicensed medicines prescriptions ranged from 12 to 71 % and 0.2 to 48 %. These authors hereby reconfirmed that (pre)term neonates were still most commonly exposed to off-label and unlicensed medicines [12].The federal US legislation and similar European initiatives have resulted in a relevant increase in pharmacological studies in children, with a subsequent significant increase in label changes. Unfortunately, too few included drug label changes specific to neonates. To further illustrate this, there were 406 pediatric label changes (Food and Drug Administration, 1997-2010), but only 23 drugs resulted in 11 labeled indications (e.g., linezolid, rocuronium, remifentanil, sevoflurane, stavudine, nevirapine) for neonates. The absence of label change was most commonly because of unproven efficacy, despite the fact that these compounds (e.g., paracetamol, caspofungin, valganciclovir) are likely relevant for neonates [14]. This may largely reflect the difficulties to proof efficacy due to heterogeneity in patients, variability in outcome variables, and uncertainty on biomarkers, in addition to demonstrating safety (risk of adverse drug events) in neonates. Despite the significant improvements in the knowledge on pharmacotherapy in older children, neonates still remain therapeutic orphans [2,14].In this issue of the journal, Campino et al. report on the rate of errors (calculation or accuracy) in intravenous medicine preparations when performed either bedside in 10 Spanish neonatal intensive care units (NICUs) or in hospital pharmacy (HP) services. The study group hereby evaluated the impact of a structured intervention (protocol standardization, education) on the number of errors and documented significant improvements in both calculation errors (1.35 to 0 %) and accuracy (54.7 and 38.3 % to 38.3 and 14.6 % in NICU and HP, respectively) [6]. This intervention paper follows on a previous paper which described a pre-intervention phase [5] and illustrates the potential impact of preventive strategies on the extent of drug errors.Development of a roadmap to improve neonatal pharmaceutical care should aim to improve the knowledge on clinical pharmacology, clinical pharmacy, and approaches to improve the knowledge and use of neonatal pharmacovigilance initiatives [1]. Another keystone component of such a roadmap should focus on neonatal drug development, i.e., drug development driven by neonatal pathophysiology (Fig. 1).

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“…Magalhães et al found that unlicensed drug use in hospitalized pediatric patients occurs in many countries, such as Brazil, Sweden, Croatia, Turkey, Estonia, Netherlands, Palestine, France, Italy, Germany, Finland, Switzerland, Serbia, Spain, Israel and England 13. In Brazil, there are few studies on the use of magistral drugs in infants and children, which are concentrated in hospitals from only three Brazilian cities: Fortaleza,9 , 14 , 15 Porto Alegre11 , 16 and Belo Horizonte 17…”

Section: Discussionmentioning

confidence: 99%

Magistral drugs in hospitalized newborns and children

Pereira

Miranda

Castilho

et al. 2016

Revista Paulista de Pediatria (English Edition)

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Objective:Study the use of magistral oral solutions and suspensions in infants and children at a university hospital.Methods:This is a descriptive study based on the analysis of the assessed hospital's magistral drug request forms regarding the patients in the neonatal ICU, Obstetrics, Pediatrics and Pediatric Emergency from January 2012 to December 2013. The frequency of drug requests and dispensation was evaluated and the consumption of each active ingredient of the preparations was expressed as number of “infant defined daily dose” (iDDD) and of iDDD/100 bed-days.Results:A total of 657 forms were analyzed - a monthly average of 27 pediatric preparations. The neonatal ICU accounted for 69.6% of these requests. Twenty-one drug items were used, of which the most common were folinic acid (88 requests), sulfadiazine (85) and captopril (73). The consumption of the active principle in these preparations varied in number of iDDD, from 7.5 (hydralazine) to 16,520.0 (folic acid), and in number of iDDD/100 bed-days in the neonatal ICU, from 0.1 (zinc sulfate) to 146.1 (folic acid).Conclusions:The constant consumption of magistral oral solutions and suspensions by newborns and children of the assessed hospital indicates the need for such preparations as a pediatric therapeutic alternative in this hospital.

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Use of off-label and unlicenced drugs in hospitalised paediatric patients: a systematic review

Cited by 99 publications

References 66 publications

Safety and Efficacy of Off-label and Unlicensed Medicines in Children

Safety and Efficacy of Off-label and Unlicensed Medicines in Children

Neonates and medicines: a roadmap to further improve neonatal pharmaceutical care

Magistral drugs in hospitalized newborns and children

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