Paracetamol versus Ibuprofen Before and After Paediatric Vaccination: A Clinical Evidence Review

Aim: Post-vaccination fever is a common adaptive immune response. Antipyretics are frequently used in paediatric practice to manage symptoms; however, concerns have emerged regarding potential interference with vaccine-induced immunogenicity, particularly when administered prophylactically. Methods: A narrative review of paediatric studies assessing prophylactic and therapeutic use of paracetamol and ibuprofen after routine vaccinations was conducted. Evidence was derived from randomized trials, systematic reviews, and real-world health-economic analyses, focusing on fever, reactogenicity, antibody titers, and clinical safety. Results: Prophylactic paracetamol consistently reduced fever but was associated with attenuated antibody titers during the primary vaccine series, notably with pneumococcal conjugate vaccines. Ibuprofen showed no measurable immunogenic suppression but is not recommended as a routine preventive strategy. Therapeutic antipyretic use, administered only after symptom onset, demonstrated no negative effect on immune responses. Ibuprofen was more effective than paracetamol for fever reduction in symptomatic children but is unsuitable in infants < 6 months. Prophylactic paracetamol is selectively justified only in high-reactogenicity contexts (e.g., 4CMenB) or in children at risk of febrile seizures. Conclusions: Routine pre-dosing of antipyretics should be avoided. A symptom-based approach optimizes immune priming, ensures clinical safety, and supports adherence to vaccination schedules.