Clozapine: Practice and REMS

Clozapine in Practice

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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.

As an update to the previous toolkit in the MHC, this version 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 

Authored by AAPP members Jonathan G. Leung, PharmD, BCPS, BCPP, Greg Deardorff, PharmD, BCPP, Megan Trout, PharmD, and Robin Hieber, PharmD, BCPP, this toolkit is intended to highlight both the evidence base available as well as strategies of clinical decision making used by expert clinicians.

Clozapine REMS Eliminated Effective 2/24/25

Beginning February 24, 2025, FDA does not expect prescribers, pharmacies, and patients to participate in the risk evaluation and mitigation strategies (REMS) program for clozapine or to report results of absolute neutrophil count (ANC) blood tests before pharmacies dispense clozapine. FDA still recommends that prescribers monitor patients’ ANC according to the monitoring frequencies described in the prescribing information. Information about severe neutropenia will remain in the prescribing information for all clozapine medicines, including in the existing Boxed Warnings.

Although the risk of severe neutropenia with clozapine still exists, FDA has determined that the REMS program for clozapine is no longer necessary to ensure the benefits of the medicine outweigh that risk. Eliminating the REMS is expected to decrease the burden on the health care delivery system and improve access to clozapine. FDA has notified the manufacturers that the clozapine REMS must be eliminated. FDA has instructed the clozapine manufacturers to formally submit a modification to eliminate the Clozapine REMS and to update the prescribing information, including removing mandatory reporting of ANC blood tests to the REMS program.

In the coming months, FDA will work with the clozapine manufacturers to update the prescribing information and eliminate the Clozapine REMS.

Summary of the November 19, 2024 Meeting of the Drug Safety and Risk Management Advisory Committee and Psychopharmacologic Drugs Advisory Committee on Clozapine REMS

A joint FDA advisory committee overwhelming voted to eliminate the risk evaluation and mitigation strategy (REMS) program designed around the risk for severe neutropenia associated with clozapine, a drug used to treat schizophrenia and schizoaffective disorder. All but one of the 15 voting panel members said the current requirements for prescribers to document absolute neutrophil count (ANC) results and for pharmacies to verify results are not necessary to ensure safe use of the atypical antipsychotic.