Clozapine Practice: Counseling Strategies and Safety Considerations

The U.S. Food and Drug Administration (FDA) eliminated the risk evaluation and mitigation strategies (REMS) program for clozapine effective February 24, 2025. This regulatory change means that the FDA no longer expects prescribers, pharmacies, and patients to participate in the REMS program or to report absolute neutrophil count (ANC) blood test results before pharmacies dispense the medication.

While the mandatory reporting requirements of the REMS program have ended, the FDA continues to recommend that prescribers monitor the ANC of their patients. This monitoring should follow the frequencies described in the medication’s prescribing information.

Information regarding severe neutropenia will remain included in the prescribing information for all clozapine medicines. This includes the existing Boxed Warnings associated with the drug.

Safety Strategies in a Post-REMS Era

With the removal of the REMS framework, clinical focus has shifted toward alternative safety and management strategies. According to reporting from October 15, 2025, strategies to maintain safety include the use of slower initial titration of the medication.

Clinicians are also encouraged to understand differences in how clozapine is metabolized across different genetic ancestry groups to better manage patient treatment.

Improving Access and Counseling

Effective counseling and education remain central to the administration of clozapine. Education for caregivers is identified as an important component of the process, although there is no single best practice for counseling on clozapine and approaches should be adapted to the situation.

Research into treatment-resistant schizophrenia has identified several institutional strategies that can increase patient access to clozapine. These facilitators include:

• The use of integrated clozapine clinics.
• The implementation of institutional directives and audits.
• Facilitated monitoring processes.
• The distribution of educational materials and the implementation of educational programs.
• Increased interaction with experts.

These systemic improvements are designed to streamline the process of initiating and managing treatment while maintaining the necessary safety oversight required for the medication.