Session: MP34: Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I
MP34-14: Medications mostly associated with urinary tract infections (UTIs): assessment of the EudraVigilance (EV) and Food and Drug Administration (FDA) Pharmacovigilance databases entries
Introduction: Drugs may have a direct causative role in triggering urinary tract infections (UTIs). The range of medications which may be responsible for UTIs is wide but little is known on those which are most frequently involved. We aimed at identifying: 1) which medications are associated with most UTIs reports; 2) within the high-risk list of medications, comparing their potential to cause UTIs through a disproportionality analysis. Methods: The Food and Drug Administration Adverse Event Reporting System (FDA-FAERS) database was queried to identify the drugs which were mostly associated with UTIs (bacterial, escherichia, staphylococcal, pseudomonal, enterococcal) reported from 10th September 2012 to 30th June 2021. Only those drugs with a minimum of 200 UTIs reports were considered for disproportionality analysis. We recorded the number of UTIs reports for such drugs reported into the Eudra-Vigilance (EV) database. EV is the system for managing and analyzing information on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). Proportional Reported Ratios (PRRs) were computed for all the drugs individuated in this way. Results: Overall, 6152 UTIs reports were identified. 1798 of them (30%) were associated with six medications which individually had a minimum of 200 reports (Table 1). Within this group of high-risk medications, Tacrolimus presented higher risk of UTIs as than prednsione (PRR 1.48 (95%CI 1.29-1.71) p<0.01) and than adalimumab (PRR 1.71 (95%CI 1.48-1.99), p<0.01). No significative differences were reported between prednisone and adalimumab (PRR 1.15 (95%CI 0.98-1.36), p=0.07) (table1). Most of the reported UTIs for drugs were presented in the 18-64 range of age (43%). Serious cases including death were 5902 (96%). On EV database analysis most UTIs reports were for Natalizumab (1433 events). Most reports for Escherichia UTIs were for Tacrolimus and Mycophenolate Mofetil, both with 78 events. Most reports for Enterococcal UTIs were for Natalizumab with 18 events. Most reports for Pseudomonal, Enterococcal and Staphylococcal UTIs were for Natalizumab respectively with 22, 18 and 11 events. Table 1: PRR for urinary tract infections according to immunosuppressors Tacrolimus Prednisone Adalimumab Mycophenolate mofetil Natalizumab Dalfampridine Tacrolimus 1,48 * 1,71* 1,77 * 2,05* 2,09* Prednisone 0,67* 1,15 * 1,19 * 1,37 * 1,40* Adalimumab 0,58 * 0,86 * 1,03* 1,19 * 1,21* Mycophenolate mofetil 0,56* 0,83* 0,97 2,04 * 2,08 * Natalizumab 0,49 * 0,72 * 0,84 * 0,86 1,02 Dalfampridine 0,48 * 0,71 * 0,82 * 0,85 * 0,98 Data are reported as PRR (95%CI), *Statistically significant PRR Conclusions: Six drugs were here identified as being associated with significant reporting levels of UTIs. Among them Tacrolimus and Natalizumab were responsible for the most reports respectively in FDA-FAERS database and in EV database and generated the strongest signal of disproportionate reporting. Our analysis highlighted similarities and differences between the two databases. Prescribers should inform those treated with these immunosuppressors about the risk of infections and its sequelae. These results require to be further integrated with clinical evidence. SOURCE OF Funding: No one
