Unveiling the hidden risks of nanomedicine-based drug delivery: a comparative evaluation of drug safety profiles of liposomal irinotecan and conventional irinotecan

Liposomal irinotecan(Nal-IRI) plays a crucial role as a nanomedicine in cancer treatment. Although it has clinically beneficial properties, Nal-IRI is accompanied by multiple adverse events (AEs) that require close observation. This pharmacovigilance study aimed to characterize and compare the safety profiles of liposomal irinotecan (Nal-IRI) and conventional irinotecan (IRI) using the FDA Adverse Event Reporting System (FAERS), focusing on identifying hidden risks of Nal-IRI in AEs. The data were extracted from the FAERS database (from Q1 2004 to Q3 2024). AE signals of Nal-IRI and IRI were mined by calculating reporting odds ratios (ROR), proportional reporting ratios (PRR), information component (IC) and empirical bayesian geometric mean (EBGM). A total of 90 Nal-IRI-positive PTs and 437 IRI-positive PTs were identified. Both exhibited stronger signals in gastrointestinal disorders and blood and lymphatic system disorders, and Nal-IRI also demonstrated stronger signals in the hepatobiliary disorders. We identified new specific AEs of Nal-IRI, cholangitis (ROR = 56.45), enterocolitis (ROR = 41.89), hematotoxicity (ROR = 18.47) and 302 off-label use reports. Meanwhile, Nal-IRI exhibited delayed toxicity, with a prolonged median AE onset time (35 days vs. 27 days for IRI) and fewer early reactions (≤7 days: 13.88% vs. 20.51% for IRI). Furthermore, Nal-IRI exhibited stronger signals in gastrointestinal disorders (e.g. vomiting, abdominal pain) in Asian populations, while European/American populations had stronger signals in hematological/hepatic adverse reactions (e.g. neutropenia, cholangitis). Nal-IRI demonstrates distinct safety challenges, including delayed toxicity, hepatobiliary risks, and population-specific vulnerabilities. These findings have revealed the unique risks associated with nanomedicine, underscoring the necessity extending pharmacovigilance.