Rising cases of drug-induced pulmonary fibrosis: Analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) database, 2000-2022.

PURPOSE: Pulmonary fibrosis (PF) is a severe, progressive disease, which may be caused by exposure to certain medications. METHODS: We queried the U.S. FDA Adverse Event Reporting System (FAERS) from 2000 to 2022, using the search terms "pulmonary fibrosis" and "idiopathic pulmonary fibrosis" and excluded reports with patients under the age of 18 years, and patients with unknown sex or age. Reports were sorted by generic drug names, counted, and plotted over time using a best-fit trendline based on an exponential function. RESULTS: From 2000 to 2022, there were 24 095 935 adverse drug events reported in FAERS, of which 17 520 (0.07%) were reported as PF. After excluding reports containing patients with unknown age (5255, 30%), sex (122, 0.7%), and age below 18 years old (155, 0.9%), our study included 11 988 reports. The mean age of the study sample was 66.5 ± 13.1 years, and 6248 patients (52.1%) were male. Plotting the 11 988 reports by year revealed an exponential best fit line (R2 = 0.88) with a positive slope over time. The top five drug classes associated with PF were disease modifying antirheumatic drugs (DMARDs, 39.4%), antineoplastic agents (26.4%), cardiovascular agents (12.6%), corticosteroids (4.6%), and immunosuppressive agents (4.0%). CONCLUSION: A 23-year analysis of the FAERS database revealed exponentially increasing adverse event reports of PF. Significant annual increases in reporting of PF suspected with DMARDs and antineoplastic agents were identified. Our study highlights important trends, which should be used to guide PF research related to drugs of potential importance.

Newer Antiseizure Medications and Suicidality: Analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) Database.

BACKGROUND: The association between antiseizure medications (ASMs) and suicidality remains controversial. Analyses of additional datasets are needed to further elucidate the complex relationship between antiseizure medications and suicidality. OBJECTIVE: The aim of this study was to compare the safety profile of newer ASMs with older ASMs through an analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, with a focus on suicidality. METHODS: We queried over 17 million reports in the FAERS database from 2012 to 2021 and identified cases involving ASMs. After removing incomplete and duplicate reports, the study cohort consisted of lacosamide (n = 7593), perampanel (n = 1813), clobazam (n = 3827), brivaracetam (n = 1166), and vigabatrin (n = 5293) compared with a control group of older ASMs (topiramate, lamotrigine, valproic acid, carbamazepine, levetiracetam; n = 71,535). Cases of suicidality (completed suicide, suicidal ideation, attempted suicide, suicidal behavior, suicidal depression) were identified in each group. Adjusted (age and sex) odds ratios (aOR) and associated 95% confidence intervals (CI) were calculated using logistic regression analysis for each new drug when compared with the control group of older ASM drugs. RESULTS: A total of 6309 cases of suicidality were identified among reports with ASMs. Most reports were sourced from healthcare professionals (5516, 87.4%). The proportion of reports involving suicidality were 210/7593 (2.8%) for lacosamide, 185/1813 (10.2%) for perampanel, 108/3827 (2.8%) for clobazam, 57/1166 (4.9%) for brivaracetam, 14/5293 (0.3%) for vigabatrin, and 5735/71,535 (8.0%) for older ASMs. Compared with older ASMs, the aOR for suicidality was 0.33 (95% CI 0.28-0.38) for lacosamide, 1.34 (95% CI 1.15-1.56) for perampanel, 0.35 (95% CI 0.29-0.43) for clobazam, 0.60 (95% CI 0.45-0.77) for brivaracetam, and 0.03 (95% CI 0.02-0.05) for vigabatrin. CONCLUSION: When compared with older ASMs, four newer ASMs (lacosamide, clobazam, brivaracetam, and vigabatrin) were found to have significantly lower odds of suicidality, while perampanel was found to significantly increase the odds of suicidality. Pronounced variability (greater than 30 fold) in the proportion of FAERS reports associated with suicidality among the drugs studied was identified. The results of this case control study of FDA adverse event reports spanning 10 years and 6309 cases of suicidality expand our understanding of the safety profile of newer ASMs.