Overview: Why a Narrative Review on Pediatric ADRs Matters
Acetaminophen and ibuprofen are among the most commonly used over-the-counter medications for fever and pain in children. While their safety profiles are well established when used correctly, reports of suspected adverse drug reactions (ADRs) in pediatric populations have risen in recent years. This trend coincides with increases in ibuprofen availability without prescription, evolving pharmacovigilance systems, and shifting parental expectations about what is “safe.” The goal of this narrative review is to synthesize available evidence on ADRs related to acetaminophen and ibuprofen in pediatric patients, and to translate findings into actionable guidance for caregivers and healthcare providers.
Methods: How the Review Was Conducted
Researchers searched PubMed and Embase using terms related to children, pediatrics, acetaminophen, ibuprofen, NSAIDs, and adverse events. From an initial pool of 337 records, 15 studies met inclusion criteria for qualitative synthesis. The review compares adverse event patterns with recent drug consumption data, notably in Italy, where ibuprofen access has expanded markedly in the past decade.
Key Findings: ADR Trends and What They Mean
1) Increasing ADR Reports with Rising Use: European pharmacovigilance data show a rise in reported ADRs for both acetaminophen and ibuprofen in children, aligned with well-documented upticks in ibuprofen use. In Italy, pediatric ibuprofen packages sold increased by about 61% since 2019, and ibuprofen use rose from 31.2% to 36.7% of pediatric antipyretic use over five years. For comparable usage, ibuprofen may have a higher rate of potentially serious adverse events than acetaminophen.
2) Common ADRs and Severity: The most frequently reported ADRs involve the gastrointestinal tract—nausea, vomiting, abdominal pain, dyspepsia, and related symptoms. While these are typically mild, NSAIDs like ibuprofen carry a risk of more serious GI complications, especially with misuse or dehydration. Ibuprofen has also been linked to renal and hepatic concerns, particularly in overdose or in children with predisposing conditions.
3) Acetaminophen Safety and Toxicity: Acetaminophen is generally safe at therapeutic doses but hepatotoxicity remains a critical risk with overdose or inappropriate use, especially when multiple acetaminophen-containing products are used concurrently. Early recognition and prompt N-acetylcysteine treatment are essential in suspected cases of overdose.
4) Infections, Dehydration, and NSAID Safety: Some studies suggest NSAIDs may alter the clinical course of certain infections or worsen dehydration-related kidney risk. Notably, reports have emerged of NSAID-related complications in specific infectious contexts, reinforcing the precaution to use the lowest effective dose for the shortest duration and to consider alternatives when infection risk is present.
5) Pediatric-Specific Considerations: ADR reporting in children is hampered by variability in data collection and dosed formulations. Case-control and retrospective studies frequently highlight misuse, dosing errors, and unsupervised access as drivers of serious outcomes. This underlines the need for age-appropriate formulations and robust education for caregivers and clinicians.
Clinical Implications: Safe Use of Antipyretics in Children
Fever management should prioritize comfort and safety over routine suppression of fever. Guidelines consistently advise treating fever primarily to relieve distress, with acetaminophen and ibuprofen serving as options when clinically indicated. Dose accuracy is critical: typical pediatric dosing is around 15 mg/kg for acetaminophen and 10 mg/kg for ibuprofen, with strict 4-6 hour dosing limits and attention to total daily intake from all sources.
Healthcare providers should offer clear counseling on recognizing signs of potential ADRs, avoiding concomitant acetaminophen-containing products, and seeking prompt care for symptoms suggesting GI bleeding, severe dehydration, or hepatic compromise. Parents should be educated on storage, packaging, and keeping medicines out of reach to reduce accidental exposures in younger children.
Limitations and Future Directions
The reviewed literature reveals heterogeneity in data collection and reporting practices across different countries. More standardized pediatric pharmacovigilance approaches are needed to quantify true incidence rates and to identify high-risk subgroups. Ongoing surveillance, better dosing guidance, and caregiver education will be essential as ibuprofen access remains high and acetaminophen use fluctuates in various settings.
Conclusion: Balancing Benefit and Safety
Acetaminophen and ibuprofen remain effective tools for pediatric fever and pain when used correctly. The observed rise in ADR reporting mirrors rising use and improved reporting systems, not necessarily a fundamental safety failure. Emphasizing appropriate dosing, duration of use, and caregiver education will help maximize benefits while minimizing harm in pediatric patients.
