Background and objectives: The US FDA and Health Canada have successively published potential red flags for acute pancreatitis caused by sodium-dependent glucose transporter 2 inhibitors (SGLT-2i). However, existing studies have focused on case reports. We aimed to assess the possible association of SGLT-2i with acute pancreatitis by analyzing postmarketing adverse events reported in the FDA adverse event reporting system (FAERS), to explore risk factors for SGLT-2i-related acute pancreatitis death, and to build a nomogram.Methods and Results: We used a disproportionality analysis of suspected acute pancreatitis-related reports in the FAERS database of patients from the use of SGLT-2i from the first quarter of 2013 to the fourth quarter of 2021. Single-factor and multi-factor logistic regression analyses were performed using the relevant clinical information of patients, and risk factors were combined with the age of patients to construct a SGLT-2i risk prediction model for acute pancreatitis-related death. A total of 757 reports were retrieved. The largest number of acute pancreatitis-related cases were caused by canagliflozin (317 reports), which was also the strongest agent associated with acute pancreatitis, with the information component (IC 2.41, lower 95% one-sided confidence interval 2.16), the reporting odds ratio (ROR 5.37, 95% two-sided confidence interval 4.8–5.99), and the empirical Bayesian geometric mean (EBGM 5.32, lower 90% one-sided confidence interval 4.85). The median time to acute pancreatitis was 54 (interquartile range [IQR] 14–131) days, and approximately 83% of adverse events occurred within 6 months. Odds ratio(OR) adjusted by acute pancreatitis and the coadministration of SGLT-2i with dipeptidyl peptidase 4 inhibitor (DPP-4i), glucagon-like peptide 1 analog (GLP-1RA), and angiotensin converting enzyme inhibitor (ACEIs) was 1.39, 1.97, and 1.34, respectively, all of which were statistically significant. Logistic regression analysis showed that different SGLT-2i type and their combinations with statins were independent risk factors for acute pancreatitis mortality in the patients (p < 0.05). The mortality risk prediction model showed good discrimination and clinical applicability in both the training set (AUC 0.708) and the validation set (AUC 0.732).Conclusion: SGLT-2i may increase the risk of acute pancreatitis especially within the first 6 months of drug administration. Combination with DPP-4i, GLP-1RA or ACEIs significantly increases the risk of acute pancreatitis. In addition, different SGLT-2i type and their combination with statins are risk factors that can predict the risk of death following acute pancreatitis.
BackgroundQuinolones are widely prescribed for the treatment or prevention of infectious diseases in children. To gain further insight into quinolone-associated adverse event (AE) in children and better protect pediatric patients, continued surveillance of safety data is essential. The purpose of this study was to characterize the safety profiles of quinolone-associated AEs in children by mining the FDA adverse event reporting system (FAERS).MethodsFAERS reports from quarter 1 of 2004 to quarter 1 of 2022 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify adverse events. Reporting odds ratios (ROR) corresponding 95% confidence intervals (CIs) and information component (IC) along with 95% CIs were calculated to detect drug–AE pairs with higher-than-expected reporting rates within the FAERS from System Organ Classes (SOCs) to Preferred Terms (PTs). Reports were considered as signals if the 95% confidence interval did not contain the null value.ResultsAfter inclusion criteria were applied, a total of 4,704 reports associated with quinolones were considered. Most FAERS reports associated with ciprofloxacin (N = 2,706) followed by levofloxacin (N = 1,191), moxifloxacin (N = 375), oflaxacin (N = 245) and ozenoxacin (N = 187). The most common age group was 12–18 years. The median weight was 39.0 kilogram. The adverse effects of quinolones emerging for SOCs primarily included Infections and infestations, gastrointestinal symptoms, blood and lymphatic system disorders, cardiac disorders, nervous system disorders, musculoskeletal and connective tissue disorders and psychiatric disorders. The most frequently AE signals at the PT level were pyrexia (N = 236), febrile neutropenia (N = 120), off label use (N = 48), drug resistance (N = 18) and cardiac arrest (N = 22) following the use of ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, and ozenoxacin, respectively. Serious oznoxacin-associated AE signals were found and have not been documented in the package insert. They included cardiac arrest (N = 22; ROR = 19.83; IC = 3.68), overdose (N = 21; ROR = 4.98; IC = 2.07), seizure (N = 16; ROR = 6.01; IC = 2.29), small for dates baby (N = 9; ROR = 14.7; IC = 3.05), completed suicide (N = 15, ROR = 18.87; IC = 3.51), asthma (N = 9; ROR = 6.69; IC = 2.24;) and hypotension (N = 9; ROR = 3.83; IC = 1.68).ConclusionThis study provided additional evidence with respect to quinolones-related AEs for children. Generally, the findings of this study are compatible with AEs recorded in package inserts. The unexpected signals of ozenoxacin justify active vigilance by clinicians and timely monitoring by pharmacovigilance experts.
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