Clozapine Support Post REMS

Clozapine has been the gold-standard treatment for refractory schizophrenia and suicidality. However, it is highly underutilized: Only 148,000 of the estimated 1.2 million people in the United States with refractory schizophrenia received the medication in 2023, according to the FDA.   In a move hoped to improve clozapine access, on June 13, 2025, the FDA officially eliminated the Clozapine REMS and all REMS operations have ceased. This means that

• Prescribers no longer need to submit patient ANC results to the Clozapine REMS.
• Pharmacies no longer need to obtain a REMS Dispense Authorization (RDA) before dispensing clozapine.
• Wholesalers and distributors no longer need to confirm a pharmacy’s REMS certification status before shipping clozapine.

• The FDA still recommends that prescribers monitor patients’ ANC according to the monitoring frequencies (unchanged from REMS era) described in a revised clozapine product prescribing information about severe neutropenia which remains in the prescribing information for all clozapine medicines, including in the existing Boxed Warnings.  A Guideline and Checklist for Initiating and Managing Clozapine and Post-REMS clozapine prescriber guidance  are useful publications for clozapine side effect monitoring guidance. Newly published Global Delphi panel on ANC and adverse drug reaction consensus guidelines can help clarify risks of off-label (U.S.) monitoring now feasible during clozapine treatment in this post-REMS era.

Clozapine is the medication of choice for those with treatment-resistant schizophrenia. Clozapine is also FDA approved for the reduction in suicidal behavior in schizophrenia or schizoaffective disorder and effective for treatment-resistant mood disorders. Despite the clinical benefits of clozapine, hesitancy to prescribe the medication is not uncommon based on perceived dangers and rigorous monitoring parameters. One method to overcome barriers of clozapine use includes ensuring adequate education about the medication. To support education, Alliance Health would like to make our prescriber community aware of the following clozapine resources:

• North Carolina Clozapine Network which includes  
  • provider consultation service available by reaching out to [email protected]
    • Clozapine Toolkit which includes sample titration schedules for both general and rapid initiation (i.e., for suicidality, violence, or other substantial risk)”

• Clozapine Toolkit on the Alliance Health website from the American Association of Psychiatric Pharmacists which contains important clozapine-related drug information such as:
• Considerations when starting clozapine
• Baseline screening parameters
• Ongoing monitoring
• Drug interactions
• Potential adverse reactions with prevention and management strategies
• An introduction to clozapine-augmentation strategies

• Clozapine Care Guide from California Correctional Health Care Services updated July 2024. While this has not yet been updated post REMS, it is an excellent comprehensive resource for clozapine therapy monitoring.
• ANC Point of Care Testing (fingerstick) is available to patients in a Durham community pharmacy. Email [email protected] for more information.