Introduction: Adverse drug reactions (ADRs) are defined as undesirable effects occurring following the administration of a drug and represent a major cause of morbidity, mortality, and healthcare costs. The primary aim of this study was to retrospectively assess the incidence, characteristics, and clinical outcomes of adverse drug reactions associated with paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) over an extended study period. A secondary objective was to identify and analyze the most frequent adverse events associated with each drug.

Patients and Methods: All patients diagnosed with ADRs who presented to our Emergency Department between 2015 and 2021 were retrospectively enrolled. Patients whose ADRs were specifically attributed to paracetamol or NSAIDs were extracted. The study population included all non-pregnant patients who met the predefined inclusion criteria.

Results: Among 897 patients with ADRs, 107 cases (62 females; mean age 37 ± 23 years) were identified as related to paracetamol and/or NSAID use. Of these, 29 patients (22 females; mean age 33 ± 22 years) presented ADRs related to paracetamol, 73 (34 females; mean age 47 ± 21 years) to NSAIDs, and 7 (6 females; mean age 31 ± 26 years) to both drug classes. Voluntary and unintentional poisoning were found to be significantly more frequent in the paracetamol group (p < 0.0001 and p < 0.002, respectively), while allergic reactions were significantly more common among patients exposed to NSAIDs (p < 0.0001). Moreover, gastritis, gastrointestinal bleeding, and renal failure were observed exclusively in the NSAID group, whereas the increase in hepatic enzyme levels showed a comparable distribution between the two groups. Finally, no significant difference was observed in hospitalization rates between patients with paracetamol-related and NSAID-related ADRs (38% vs. 27%, respectively; p = ns).

Conclusions: This study confirms that ADRs are more frequent in female patients and that paracetamol and NSAIDs exhibit distinct toxicity profiles. Paracetamol is generally safer with respect to unintentional ADRs, whereas NSAIDs are more commonly associated with gastrointestinal, allergic, and renal complications. Since gut microbiota alterations may play a pivotal role in the occurrence of ADRs, further studies are needed in order to test how they may increase the risk.