Comparison of Adverse Event Profiles of Amphotericin B Formulations Using Real-World Data.

Amphotericin B deoxycholate (AMPH-B) is a polyene macrolide with antifungal activity. Liposomal AMPH-B (L-AMB) was developed to reduce side effects while maintaining antifungal activity. This study was aimed at evaluating and comparing the adverse event profiles of AMPH-B and L-AMB using a spontaneous reporting system. We analyzed the adverse event reports of AMPH-B and L-AMB from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Case report counts of adverse events were generated according to the preferred terms of the Medical Dictionary for Regulatory Activities (MedDRA). Standardized MedDRA queries (SMQs) and system organ classes (SOCs) were used to compare the organ-specific adverse event profiles of AMPH-B and L-AMB. The reporting odds ratio and proportional reporting rate were used to detect pharmacovigilance signals. The FAERS database contains 21,173,818 cases from January 2004 to March 2024. Adverse events were reported in 2438 cases receiving AMPH-B treatment and 3344 cases receiving L-AMB treatment, including 848 and 1591 cases receiving intravenous AMPH-B and L-AMB injections, respectively. The most frequently reported drug-related adverse event in the AMPH-B and L-AMB groups was hypokalemia. SOCs with statistically significant differences were "Inv" (laboratory tests), "Resp" (respiratory, thoracic, and mediastinal disorders), "Genrl" (general and systemic disorders and conditions at the site of administration), "Card" (cardiac disorders), and "Blood" (blood and lymphatic system disorders). No statistically significant difference was observed in the SMQ profile of adverse events in "Renal" (renal and urinary disorders) and "Hepat" (hepatobiliary disorders) between the L-AMB and AMPH-B formulations in this study. Based on real-world data from FAERS, adverse event profiles of AMPH-B and L-AMB were compared. No statistically significant difference was observed in the SMQ profile of adverse events in the renal and hepatic SOCs between the L-AMB and AMPH-B formulations. Our results suggest that L-AMB is more tolerated by the kidneys than AMPH-B.
Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: The authors disclose the receipt of the following financial support for the research, authorship, and/or publication of this article. This research was partially supported by JSPS KAKENHI,Grant Numbers 23H05264, 21K11100, and 21K06646. The funders played no role in the study design, data collection and analysis, decision to publish this article, or article preparation. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.
(Copyright © 2024, Nokura et al.)