Drug unavailability increases off-label prescribing in the pediatric population in Slovakia

Czech version

Authors: Michala Hrončová ^1,2; Simona Valášková ²; Andrea Gažová ²
Authors‘ workplace: Poliklinka Tehelná, Lekáreň Ferox, Bratislava ¹; Ústav farmakológie a klinickej farmakológie, Lekárska fakulta Univerzity Komenského, Bratislava ²
Published in: Čes. slov. Farm., 2026; 75, 14
Category: Original Articles
doi: https://doi.org/10.36290/csf.2026.010

Overview

Drug shortages may lead to interruption of ongoing treatment, delays in therapy initiation, or the need to modify therapeutic regimens. This represents a current and persistent problem that requires systematic and long-term solutions, as it may be a significant contributing factor to off-label prescribing. Between 2018 and 2020, the occurrence of drug shortages increased up to twentyfold, accompanied by a growing demand for essential medicines. The aim of this study was to analyse the occurrence of off-label prescribing in the paediatric population in a community pharmacy and to assess a possible association between the unavailability of a selected medicine and an increase in off-label use of a therapeutic alternative. A retrospective analysis was conducted using data obtained from pharmacy software and the national eHealth system for the period 2021–2024. A total of 6,366 paediatric patients were included in the analysis, with off-label prescribing identified in 705 cases (11.07%). Off-label use most frequently involved antibiotics for systemic use and ophthalmological medicines, with the highest proportion of off-label prescribing within an ATC group observed for ophthalmological drugs. In evaluating the relationship between the unavailability of Pamycon and increased off-label prescribing of Uniflox 0.3% eye drops, no statistically significant association was demonstrated (p > 0.05). Off-label prescribing is a common component of paediatric pharmacotherapy and is influenced by multiple factors beyond medicine availability alone. Pharmacists play an important role in ensuring safe treatment by identifying potential risks, educating parents or caregivers, and supporting the rational use of medicines. Strengthening collaboration among healthcare professionals and consistent pharmacovigilance are essential for improving the safety of off-label treatment in children.

Keywords:

off-label – drug shortages – paediatric population – prescriptions – age group

Sources

1.Heads of Medicines Agencies (HMA). Availability of Medicines for Human Use [Internet]. London: HMA; [cited 2025 Oct 15]. Available from: https://www.hma.eu/human-medicines/availability-of-medicines.html

2.EURÓPSKY PARLAMENT A RADA EURÓPSKEJ ÚNIE. Nariadenie (ES) č. 1901/2006 Európskeho parlamentu a Rady z 12. decembra 2006 o liekoch na pediatrické použitie a o zmene a doplnení nariadenia (EHS) č. 1768/92, smernice 2001/20/ES, smernice 2001/83/ES a nariadenia (ES) č. 726/2004. Úradný vestník Európskej únie. 2006, L 378, s. 1–19.

3.EUROPEAN MEDICINES AGENCY. Paediatric Committee (PDCO) –⁠ role and responsibilities [online]. Amsterdam: EMA, 2021 [cit. 2026-02-08]. Dostupné na: https://www.ema.europa.eu/en/committees/paediatric-committee-pdco

4.EUROPEAN MEDICINES AGENCY. Paediatric investigation plans (PIPs) –⁠ guidance and procedural information [online]. Amsterdam: EMA, 2025 [cit. 2026-02-08]. Dostupné na: https://www.ema.europa.eu/en/human-regulatory-overview/research-and-development/paediatric-medicines-research-and-development/paediatric-investigation-plans

5.EUROPEAN MEDICINES AGENCY. Paediatric-use marketing authorisations (PUMA) [online]. Amsterdam: EMA, 2025 [cit. 2026-02-08]. Dostupné na: https://www.ema.europa.eu/en/human-regulatory-overview/marketing-authorisation/paediatric-medicines-marketing-authorisation/paediatric-use-marketing-authorisations

6.European Parliament. Report on the shortage of medicines –⁠ how to address an emerging problem (2020/2071(INI)) [Internet]. Brussels: European Parliament; 2020 [cited 2025 Oct 15]. Available from: https://www.europarl.europa.eu/doceo/document/A-9-2020-0142_EN.html

7.European Medicines Agency. First version of the Union list of critical medicines agreed to help avoid potential shortages in the EU [Internet]. Amsterdam: EMA; 2023 [cited 2025 Oct 15]. Available from: https://www.ema.europa.eu/en/news/first-version-union-list-critical-medicines-agreed-help-avoid-potential

8.Slovenská republika. Zákon č. 363/2011 Z. z. o rozsahu a podmienkach úhrady liekov, zdravotníckych pomôcok a dietetických potravín na základe verejného zdravotného poistenia [Internet]. Bratislava: Zbierka zákonov Slovenskej republiky; 2011 [cited 2025 Oct 15]. Available from: https://static.slov-lex.sk/static/SK/ZZ/2011/363/20170101.html

9.Slovenská republika. Zákon č. 362/2011 Z. z. o liekoch a zdravotníckych pomôckach a o zmene a doplnení niektorých zákonov [Internet]. Bratislava: Zbierka zákonov Slovenskej republiky; 2011 [cited 2025 Oct 15]. Available from: https://www.slov-lex.sk/pravne-predpisy/SK/ZZ/2011/362/

10.Breitkreutz J. European perspectives on pediatric formulations. Clin Ther. 2008 Nov;30(11):2146-54. doi: 10.1016/j.clinthera.2008.11.016. PMID: 19108802.

11.Yuan X, Gao J, Yang L, Tan Y, Bajinka O. Off-label and unapproved pediatric drug utilization: A meta-analysis.Experimental and Therapeutic Medicine. 2024;28(5):412. doi:10.3892/etm.2024.12701.

12.Matalová P, Belfínová L, Vrbicová K, Fürstová J, Wawruch M. Zhodnocení incidence unlicensed a off-label předpisu léčiv u dětí. Klinická farmakologie a farmacie. 2024;38(2):52–54. doi: 10.36290/far.2024.008.

13.SCHWEIGERTOVÁ, J., et al. Off-label and unlicensed use of medicinal products in hospitalised neonates and infants in Slovakia: a cross-sectional study. Acta Paediatrica. 2016, roč. 105, č. 6, s. e210–e215. DOI: 10.1111/ped.12771.

14.Smith J., Müller P., García L., Novak T. Off-label prescribing in paediatric patients. Acta Paediatrica, 2021, roč. 110, č. 11, s. 3255–3263. DOI: 10.1111/ped.12771.

15.Petkova V, Georgieva D, Dimitrov M, Nikolova I. Off-Label Prescribing in Pediatric Population-Literature Review for 2012-2022. Pharmaceutics. 2023 Nov 21;15(12):2652. doi: 10.3390/pharmaceutics15122652. PMID: 38139994; PMCID: PMC107