Impact of FDA’s Enforcement Discretion of Clozapine REMS Program on Clozapine Adverse Event Reporting
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Introduction
In response to the COVID-19 pandemic, the FDA announced enforcement discretion of the clozapine Risk Evaluation and Mitigation Strategy (REMS) program on March 22, 2024. The impact of these changes on rates of Clozapine related adverse-events and reporting pattern has not been examined to-date. Using the FDA Adverse Event Reporting System (FAERS) database, we examined the effect of this regulatory change on the reporting patterns of Clozapine-related adverse events.
Methods
Data from the FAERS database from January 2018 to June 2024 was obtained. Interrupted time-series models were employed to evaluate the total number of reported adverse events and event-specific rates for death, agranulocytosis, neutropenia, and myocarditis, with March 22, 2020, as the index date for FDA enforcement discretion.
Results
FAERS database reports were predominantly from USA (41.63%), with majority of reports submitted by physicians (37.88%) and pharmacists (37.83%). Total reported counts per month and death count per month did not show significant changes in trend. The reported death proportion and myocarditis count showed a significant downward trend (p = 0.002 and p = 0.005, respectively). No significant trend changes were seen in reporting of agranulocytosis and neutropenia (count per month and proportion).
Discussion
The FDA’s enforcement discretion of clozapine REMS program during the COVID-19 pandemic was associated with a significant reduction in reporting of clozapine-induced myocarditis and death, but not of agranulocytosis or neutropenia. Whether these changes reflect true change in rates, preferential attribution of these adverse-events to COVID-19 or change in reporting patterns warrant further verification.
