Safety assessment for ibuprofen using disproportionality analysis: a decade of data from the Romanian national...

The aim of this study was to evaluate the adverse reactions associated with ibuprofen, one of the most widely used analgesic-antipyretic agents, in comparison with other nonsteroidal anti-inflammatory drugs (NSAIDs). In Romania, most pharmaceutical forms of ibuprofen are available over the counter, except for parenteral formulations and high-dose oral forms (800 mg), which require a prescription.

Descriptive and disproportionality methods were conducted on reports associated with ibuprofen and six other NSAIDs, submitted to the National Agency for Medicines and Medical Devices of Romania between 2015 and 2024 by healthcare professionals and patients. The type and the frequency of adverse reactions, and their classification according to the System Organ Classification were analyzed. For the disproportionality analysis, the reporting odds ratio and 95% confidence interval were used to compare the disproportional reporting ADRs related to ibuprofen with that of other six NSAIDs.

From the total number of reports (n = 128), 44 were related to ibuprofen, with an annual mean of 4.4 ± 2.91, indicating greater reporting variability. Within 15 reports, several serious events were recorded 10 required hospitalization or prolongation of hospitalization, 5 were life-threatening, 3 were associated with other severe medical conditions, and one resulted in the patients' death. The safety profile of ibuprofen shows a predominance of gastrointestinal adverse reactions (n = 31) over immunological (n = 18), cutaneous (n = 18), or neurological reactions (n = 7). However, the disproportionality analysis, limited by the relatively small number of reports, suggests a higher disproportional reporting of gastrointestinal disorders for ibuprofen than for etoricoxib (ROR 4.74; 95% CI 1.72-13.03). In contrast, a lower disproportional reporting skin and soft tissue ADRs related to ibuprofen, compared with diclofenac (ROR 0.32; 95% CI 0.11-0.95) and celecoxib (ROR 0.17; 95% CI 0.05-0.54), was observed.

The reported adverse reactions were consistent with the established safety profile of ibuprofen and are largely described in the Summary of Product Characteristics, with no new safety signals identified. However, this study adds national real-world pharmacovigilance evidence by demonstrating a higher disproportional reporting of gastrointestinal disorders compared with etoricoxib and by highlighting children and adolescents as the most frequently represented reporting population. These findings contribute to a better understanding of ibuprofen safety patterns in routine clinical practice in Romania. The results should be interpreted in the context of inherent limitations, such as underreporting of adverse reactions and the difficulty in establishing causality, particularly for patient-reported cases, which may introduce a higher degree of subjectivity.