Abstract
BACKGROUND: Paracetamol and ibuprofen are widely used for fever and pain in children, but real-world prescribing often deviates from guidelines, leading to potentially avoidable complications and healthcare costs. OBJECTIVES: To estimate the clinical and economic burden associated with inappropriate use of paracetamol and ibuprofen in Italian pediatric care and to identify high-risk clinical scenarios in which safer prescribing may reduce complications. METHODS: A retrospective analysis was conducted on national hospital discharge records (2010-2016), focusing on DRGs and ICD-9-CM codes linked to adverse events following antipyretic or NSAID use in children aged 0-17. A qualitative assessment was also carried out through expert consultation to contextualize findings. RESULTS: Among 999,739 hospital discharges, 4,308 cases (0.43%) developed complications within three years. ENT procedures and renal diagnoses showed the highest complication rates and costs. Children under three accounted for the largest share of healthcare expenditure. A scenario analysis using pneumonia data suggested that up to 3,000 complications and €10 million in costs could be avoided with more selective NSAID use. Experts recommended prioritizing paracetamol in high-risk scenarios, including dehydration, respiratory infections, and varicella. CONCLUSIONS: Inappropriate use of antipyretics in pediatric care is associated with a measurable clinical and financial burden. Greater adherence to prescribing recommendations, especially in vulnerable populations, can improve outcomes and reduce costs. Educating caregivers and harmonizing clinical practices are key priorities.