{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T12:00:25Z","timestamp":1776081625456,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: Adverse drug reactions are associated with off-label (OL) and unlicensed (UL) drug use in children. Methods: We conducted a retrospective observational pharmacovigilance study based on individual case safety reports (ICSRs) and adverse drug reactions (ADRs) from VigiBase for patients aged 0\u201317 years to evaluate reporting patterns associated with off-label and unlicensed suspected drugs reported in Serbia. Results: Over 14 years, 2037 pediatric ICSRs comprising 4257 ADRs were reported. Infants (28 days\u201323 months) accounted for just over half of ICSRs, and systemic anti-infectives and vaccines dominated suspected drugs. Overall, 9.7% of ADRs were serious, including 12 fatal outcomes, with serious ADRs reported more often for non-vaccine than vaccine suspected drugs. Off-label and unlicensed suspected drug records accounted for 10.8% and 1.9% of suspected drug records, respectively, and had higher proportions of serious ADRs than on-label or licensed use (off-label 12.1% vs. on-label 9.4%, p = 0.04; unlicensed 22.9% vs. licensed 9.4%, p &lt; 0.001). In the adjusted ICSR-level logistic regression, neonatal age was the strongest independent predictor of seriousness, with approximately threefold higher odds of a serious case compared with children (aOR 3.04, 95% CI 1.55\u20135.98). Conclusions: Although off-label and unlicensed drugs accounted for a minority of pediatric reports, they were associated with a higher proportion of serious reported ADRs, particularly in the neonatal period. These findings should be interpreted as pharmacovigilance reporting patterns rather than incidence-based estimates or proof of causality.<\/jats:p>","DOI":"10.3390\/children13040536","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T10:19:14Z","timestamp":1776075554000},"page":"536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serious Adverse Drug Reactions Associated with Off-Label and Unlicensed Drug Use in Children: A 14-Year Analysis of VigiBase Reports from Serbia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7365-6110","authenticated-orcid":false,"given":"Jovana","family":"Joksimovic","sequence":"first","affiliation":[{"name":"Human Medicines Centre, Medicines and Medical Devices Agency of Serbia (ALIMS), 11221 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7855-5182","authenticated-orcid":false,"given":"Dusan Mihajlo","family":"Spasic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Kukuric","sequence":"additional","affiliation":[{"name":"Department of Emergency Radiology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milica","family":"Bajcetic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.therap.2017.11.012","article-title":"Pharmacovigilance in pediatrics","volume":"73","author":"Bouquet","year":"2018","journal-title":"Therapies"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1007\/s11096-018-0657-1","article-title":"An historical overview over Pharmacovigilance","volume":"40","author":"Fornasier","year":"2018","journal-title":"Int. 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