Pharmacovigilance of triazole antifungal agents: Analysis of the FDA adverse event reporting system (FAERS) database

Abstract

Triazole antifungal drugs (TAD) are widely used to treat invasive fungal infections due to their broad antifungal spectrum and low toxicity. Despite their preference in the clinic, multiple Adverse Events (AE) are still reported each year. Objective: We aimed to characterize the distribution of Adverse Events associated with Triazole antifungal drugs in different systems and to identify Important Medical Events (IME) signals for Triazole antifungal drugs. Methods: The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) was queried for Adverse Events related to Triazole antifungal drugs from 2012 to 2022. The Adverse Events caused by all other drugs and non-TAD antifungal drugs were analyzed as references. Reporting odds ratio and Bayesian confidence propagation neural network of information components were used to evaluate the association between Triazole antifungal drugs and Important Medical Events. Visual signal spectrum is mapped to identify potential adverse reaction signals. Results: Overall, 10,262 Adverse Events were reported to be associated with Triazole antifungal drugs, of which 5,563 cases were defined as Important Medical Events. Common adverse drug reactions (ADR) mentioned in the instructions such as delirium and hypokalemia were detected, as well as unlabeled ADRs such as rhabdomyolysis and hepatitis fulminant. Cholestasis, drug-induced liver injury, QT interval prolongation and renal impairment have notable signals in all Triazole antifungal drugs, with 50 percent of patients developing a severe clinical outcome. Isavuconazole had the lowest signal intensity and demonstrated a superior safety profile. Conclusion: Most results are generally consistent with previous studies and are documented in the prescribing instructions, but some IMEs are not included, such as hepatitis fulminant. Additional pharmaco-epidemiological or experimental studies are required to validate the small number of unlabeled ADRs. TAD-related Important Medical Eventshave a considerable potential to cause clinically serious outcomes. Clinical use of Triazole antifungal drugs requires more attention.

Evaluating cardiac disorders associated with triazole antifungal agents based on the US Food and Drug Administration Adverse Event reporting system database

“…Moreover, there were only one cardiac PT associated with isavuconazole, and no new cardiac PTs in this study. A study conducted by Zhou et al (2022) analyzed the distribution of AEs associated with TAAs in different SOCs from 2012 Q4 to 2022 Q1, and this analysis about the top 30 IMEs induced by TAAs based on all other drugs as analysis contexts showed that the number of the observed significant cardiac PT signals for fluconazole, voriconazole, itraconazole, posaconazole, and isavuconazole was 3, 4, 5, 4, and 1, respectively. Consistent with our results, it showed that isavuconazole had less cardiac PT signals compared to the other four TAAs.…”

“…Many adverse events (AEs) have been reported in their postmarketing application, mainly including hepatotoxicity, gastrointestinal reaction, renal impairment, rash, and cardiac disorders (Amsden and Gubbins, 2017;Shen et al, 2022;Yu and Liao, 2022;Zhou et al, 2022). Among these, cardiac disorders were a significant systemic organ class (SOC) signals for important medical events (IMEs) induced by TAAs (Zhou et al, 2022). Cardiac disorders are common clinical conditions associated with high mortality rates (Shinomoto et al, 2022).…”

“…There have been many reports about TAA-induced cardiac disorders in recent years. It included arrhythmia, bradycardia, cardiac arrest, qt interval prolongation, torsade de pointes et al (Salem et al, 2017;Mellinghoff et al, 2018;Zhou et al, 2022;Yuan et al, 2023). Among these, qt interval prolongation was mainly found in fluconazole, voriconazole, itraconazole, and posaconazole (Yu and Liao, 2022).…”

“…For example, itraconazole induced heart failure when it was administrated at the dosage of 200 mg twice a day or once a day (Paleiron et al, 2011;Abraham and Panda, 2018). Isavuconazole shortened the qt interval according to the drug label, however, it was demonstrated that isavuconazole could induce qt interval prolongation at regular dosage as specified in the drug label in recent years (Marty et al, 2016;Zhou et al, 2022). Thus, it is of important significance to explore new cardiac AEs to ensure drug safety.…”

Postmarket safety profile of suicide/self-injury for GLP-1 receptor agonist: a real-world pharmacovigilance analysis

“…As a result, potential safety concerns might arise in everyday clinical practice that were not evident during the more controlled and structured environment of clinical trial evaluations [28]. Therefore, postmarketing surveillance and real-world evidence play a crucial role in continuously monitoring the safety and effectiveness of medications once they are in widespread use [29][30][31]. The analysis of pharmacovigilance for a drug, utilizing postmarketing safety databases like the FAERS, plays a crucial role in the ongoing management of risks by detecting safety signals that may not have been identified during the drug's clinical development phase [10,14,[32][33][34][35].…”