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Background/Aim: In paediatric clinical practice, paediatricians often need to prescribe medicines outside the terms of their marketing authorisation, as the authorised information may not cover a specific age group, indication, dose, or route of administration. Additionally, a suitable paediatric formulation may be unavailable. A recent analysis of Kinderformularium.DE, a database providing evidence-based information on paediatric medications, found that 37% of its age- and indication-specific dosing recommendations were classified as off-label [1].

This project aimed to synthesise evidence from reviews published over the past decade on the prevalence and risks of off-label and unlicensed drug use in paediatrics.

Methods: We conducted a narrative review, using a targeted PubMed search to identify relevant review articles from 2014 to 2025. Data were systematically extracted and compared with particular attention to definitions, study populations, settings, and outcome measures. Due to substantial methodological and clinical heterogeneity, prevalence estimates were not statistically pooled and should not be interpreted as directly comparable. Additionally, the primary studies cited in the included reviews were identified and examined for evidence concerning risk-related outcomes, which were not addressed consistently across the reviews.

Results: Of 1,534 citations screened, 10 reviews comprising 136 unique primary studies were included. Substantial heterogeneity regarding definitions, populations, settings, and outcome measures was detected. Reported off-label use ranged from 1.2% to 99.7%, and unlicensed use from 0% to 79.0%. Age- and setting-related patterns were evident but context-dependent, with the highest and most consistent rates of off-label use observed among neonatal and intensive-care populations. Evidence regarding risks was limited. The available observational evidence from 13 primary studies suggested that off-label or unlicensed medicines may be associated with adverse drug reactions in some settings. However, the magnitude – and possibly the presence – of this association, the causality and generalizability remain uncertain, due to variability in patient characteristics, treatment context, medicine burden and the type of off-label use.

Discussion/Conclusion: Overall, off-label drug use is common in paediatric practice, but substantial heterogeneity limits comparisons between studies and settings. Quantitative evidence on associated risks remains insufficient to reliably determine their magnitude, clinical significance, or causality. Robust general estimates will require harmonised definitions and study methodology. In clinical practice, accessible, evidence-based information should support individual treatment decisions and clearly indicate when evidence is limited or when additional safety monitoring may be warranted.

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