Risk Factors for Unlicensed and Off-Label Drug Use in Children Outside the Hospital

Schirm, Eric; Tobi, Hilde; Berg, Lolkje Theodora Wilhelmina de Jong-van den

doi:10.1542/peds.111.2.291

Cited by 91 publications

(67 citation statements)

References 17 publications

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“…First, the study settings have varied; some have focused on admissions [4], some have included only inpatients [5][6][7], others have used a combination of in-patients and new admissions [2], while others have been community-based [8,9]. There is some evidence that off-label prescribing is more prevalent in children who receive a greater number of prescriptions from their GPs, and in those who require a greater number of referrals to specialist care, and indeed in specialist care per se [15,16]. Second, given the differences in study settings, the types of patients surveyed have been different.…”

Section: Tablementioning

confidence: 99%

Adverse drug reactions and off-label and unlicensed medicines in children: a prospective cohort study of unplanned admissions to a paediatric hospital

Bellis

Kirkham

Nunn

et al. 2014

Br J Clin Pharmacol

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AIMSTo examine the impact of off-label and unlicensed (OLUL) prescribing on adverse drug reactions (ADRs) causing unplanned admissions to a paediatric hospital. METHODSPrescription data from a 12 month prospective cohort study of ADRs detected in children admitted to a paediatric hospital were scrutinized. The relative risk for off-label and unlicensed medicines being implicated in an ADR was calculated. Logistic regression analyses were carried out with exposure to off-label and unlicensed medicines and number of off-label and unlicensed medicines administered as predictor variables. RESULTSOff-label and unlicensed medicines were more likely to be implicated in an ADR than authorized medicines (relative risk 1.67, 95% CI 1.38, 2.02, P < 0.001). There was a 25% increase in ADR risk (95% CI 1.16, 1.35, P < 0.001) with each additional authorized medicine and 23% (95% CI 1.10, 1.36, P < 0.001) with each additional off-label or unlicensed medicine. Logistic regression analysis focusing on non-oncology patients demonstrated that the number of authorized medicines (odds ratio 1.33, 95% CI 1.23, 1.44, P < 0.001), but not the number of off-label and unlicensed medicine courses, was a predictor of ADR risk. CONCLUSIONSIn a heterogeneous population of children admitted to a secondary/tertiary hospital, off-label and unlicensed medicines are more likely to be implicated in an ADR than authorized medicines. This was largely driven by ADRs related to drugs used in oncological practice, where the usage of off-label or unlicensed medicines was associated with a higher ADR risk than in non-oncological areas. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The use of off-label and unlicensed (OLUL) medicines in children is common and is a potential risk factor for adverse drug reactions (ADRs).• Previous large studies have focused on inpatients or community-based practice. • There have been two studies which included unplanned admissions but, due to their small size, they were unable to assess properly the contribution of off-label and unlicensed medicines. WHAT THIS STUDY ADDS• In a study of ADR-related admissions to a paediatric hospital, the number of medicines prescribed was a predictor of risk.• Off-label and unlicensed medicines were also more likely to be implicated in an ADR than authorized medicines, but this was driven by the higher risk of ADRs to oncology drugs prescribed in an off-label or unlicensed manner than non-oncology drugs.

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Section: Tablementioning

confidence: 99%

Adverse drug reactions and off-label and unlicensed medicines in children: a prospective cohort study of unplanned admissions to a paediatric hospital

Bellis

Kirkham

Nunn

et al. 2014

Br J Clin Pharmacol

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“…On the other hand it has been suggested that offlabel use might weaken the interest of pharmaceutical companies to conduct costly trials and apply for marketing authorization if a product has already widely penetrated the market [6]. The extent and problems of off-label and unlicensed use of medicines in children are well documented [7][8][9].The effects of a later paediatric labelling and age-appropriate formulations (dosage forms) on the extent of off-label and on-label use would be of high interest. Unfortunately, longitudinal studies on the dynamics and development of off-label use in children are lacking.…”

Section: Introductionmentioning

confidence: 99%

Evolution of paediatric off‐label use after new significant medicines become available for adults: a study on triptans in Finnish children 1994–2007

Lindkvist¹,

Airaksinen²,

Kaukonen

et al. 2011

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Off-label use in children is widespread. New medicines lack marketing authorization for paediatric use, even when they represent significant therapeutic advantages and are intended for treatment of conditions common in children.• Until now no information exists on how off-label use in children develops over time after a significant new medicine is approved for adults and what happens when it is later labelled for one paediatric age group. WHAT THIS STUDY ADDS• Off-label use of a new significant medicine begins in adolescents and extends to younger children with delay. First marketing authorization to adolescents, providing a more child-friendly formulation, results in increase of off-label use in younger children, and has limited effect on total off-label use. AIMTo investigate the evolution of paediatric off-label use after a therapeutically new group of medicines for a common condition becomes available for adults but is labelled for children with a delay of several years. METHODSTriptans were used as a model, because migraine is common in children, and is the only indication for triptans. Data on all triptan prescriptions 1994-2007 were extracted from the nationwide Finnish Prescription Register. Prescriptions for children were compared over time. RESULTS CONCLUSIONSWhen a new significant medicine becomes available in adults, off-label use in children starts slowly but continues to extend to younger children reaching a market size which is little influenced by late appearance of a labelled product. Paediatric treatment remains dominated by off-label use despite labelling of a product in an age appropriate formulation to the most relevant age group.British Journal of Clinical Pharmacology DOI:10.1111DOI:10. /j.1365DOI:10. -2125DOI:10. .2010 Br J Clin Pharmacol / 71:6 / 929-935 / 929

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“…Prescriptions by specialists (outpatient), prescriptions for new drugs, prescriptions for drugs with a low use in the paediatric population, and prescriptions for infants were risk factors for using a systemic drug unlicensed or off-label in that study [27]. Since the indications are not available in pharmacy dispensing data, the indication for prescription of a drug was not evaluated.…”

Section: Discussionmentioning

confidence: 99%

Unlicensed and off-label prescription of respiratory drugs to children

Jong¹,

Eland²,

Sturkenboom³

et al. 2004

Eur Respir J

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Many respiratory drugs are not available in formulations suitable for infants and toddlers. Efficacy and safety research is mostly restricted to older children. However, respiratory drugs are frequently used in children for common diseases like asthma, upper and lower respiratory tract infections, rhinitis and sinusitis. The unlicensed and off-label use of respiratory drugs in children were studied.A population-based cohort study was conducted by using the computerised medical records in the Integrated Primary Care Information project. The study population comprised a random sample from all children aged 0-16 yrs who were registered with a general practitioner in 1998. All prescriptions for respiratory drugs during the study period were classified according to their licensing and off-label status.The study population comprised 13,426 patients (51.7% male, median age 8.7 yrs), of whom 2,502 (19%) received 5,253 prescriptions for respiratory drugs in 1998. A total of 3,306 (62.9%) prescriptions concerned licensed drugs. Of the remaining 1,947 prescriptions (37.1%), 882 (16.8%) were unlicensed for use in children, and 1,065 (20.3%) were prescribed off-label. The 1-yr cumulative risk of receiving an unlicensed or off-label prescription was 45% among children with at least one prescription for a respiratory drug.This population-based study showed that a large proportion of respiratory drugs prescribed by the general practitioner are unlicensed for use in children, or licensed but prescribed in an off-label manner. Results have to be interpreted with caution because they may unjustly suggest inaccurate prescribing, whereas it may be difficult to treat children with respiratory symptoms and diseases, because for many respiratory drugs paediatric data on safety and efficacy are insufficient. These findings underline the importance of research on suitable formulations, dosages and efficacy of respiratory drugs in children. The extent and nature of unlicensed and off-label drug prescription in paediatric clinical care has been the subject of several surveys in Europe [1][2][3][4][5][6][7] and these consistently showed that a very large proportion of prescribed drugs are either unlicensed for use in children or used outside the terms of the product license ("off-label"). Several studies also provide information on the extent of this type of drug prescription in children with respiratory diseases, but information provided is often limited.Respiratory drugs are used for several of the most common paediatric diseases such as asthma, upper and lower respiratory tract infections, rhinitis and sinusitis; conditions that are treated in general practice rather than in clinical care [8][9][10][11][12]. Previous research by the present group revealed that 70% of available respiratory drugs in the Netherlands are not fully licensed for use in children, and many of these (80%) are registered only for specific age/weight groups [13]. Many of the children with respiratory problems present themselves long before they have reach...

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Risk Factors for Unlicensed and Off-Label Drug Use in Children Outside the Hospital

Abstract: Efforts to improve pediatric labeling are important and need full support. The present results can be used to focus these efforts.

Cited by 91 publications

References 17 publications

Adverse drug reactions and off-label and unlicensed medicines in children: a prospective cohort study of unplanned admissions to a paediatric hospital

Adverse drug reactions and off-label and unlicensed medicines in children: a prospective cohort study of unplanned admissions to a paediatric hospital

Evolution of paediatric off‐label use after new significant medicines become available for adults: a study on triptans in Finnish children 1994–2007

Unlicensed and off-label prescription of respiratory drugs to children

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