Clozapine is the only medication approved by the FDA for treatment resistant schizophrenia, and is widely underutilized in the US (Olfson et al. 2016). One serious possible side effect of clozapine is severe neutropenia, which is defined as an absolute neutrophil count of <500/µL. A recent meta-analysis found the incidence of clozapine-induced severe neutropenia was 0.9%, with 1/7700 people exposed to clozapine dying from severe neutropenia (Myles et al. 2018). To help manage the risk of neutropenia, clozapine has a Risk Evaluation and Mitigation Strategy (REMS) mandated by the FDA. Currently there are 61 available REMS programs (U.S. Food and Drug Administration), and changes or updates to REMS systems can have important implications. For example, after the FDA approved a new benign ethnic neutropenia treatment algorithm (Clozapine REMS 2014), a study found that patients with schizophrenia on clozapine would be less likely to need treatment interruption after the new guidelines were released (Sultan et al. 2017). Effective November 15, 2021, a new clozapine REMS system will replace the existing system. The new system will require all prescribers and pharmacists to re-certify, and additionally, all patients must be re-enrolled. Failure to re-enroll or re-certify may lead to clozapine interruption, which could result in significant consequences and negative outcomes for individuals stabilized on clozapine. This webinar will provide an update on clozapine-induced neutropenia, an overview of the changes coming to clozapine REMS (from the prescriber and pharmacist perspectives), and will discuss strategies for how prescribers may navigate these changes successfully. The presenters will also have an open discussion with participants to listen to their concerns and brainstorm potential solutions on the new program.