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  5. Frequently Asked Questions | Clozapine REMS Modification
  1. Postmarket Drug Safety Information for Patients and Providers

Frequently Asked Questions | Clozapine REMS Modification

Latest Update

February 24, 2025 - Beginning today, 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. 

Past Updates on Clozapine

Clozapine Risk Evaluation and Mitigation Strategy (REMS) Advisory Committee Meeting 2024

August 9, 2024 - FDA will be hosting an in-person advisory committee meeting on November 19, 2024, to discuss reevaluation of the Clozapine risk evaluation and mitigation strategy (REMS). FDA looks forward to the committee’s advice regarding possible changes to the Clozapine REMS to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of clozapine.  Background information, links to webcasts, and instructions on presenting or attending the meeting can be found at the meeting announcement.  

September 21, 2023 - As part of our regular review of all risk evaluation and mitigation strategies (REMS), and in light of the Agency’s continued exercise of enforcement discretion with respect to certain aspects of the Clozapine REMS, FDA is conducting a thorough reevaluation of the Clozapine REMS to determine whether the REMS can be modified to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of clozapine.

As part of this reevaluation, FDA has funded a study by Brigham and Women’s Hospital that includes an analysis of clozapine utilization, adherence to the REMS requirement for monitoring of absolute neutrophil count (ANC), and clinical outcomes. In addition, FDA is conducting a study in collaboration with the Veterans Health Administration to better understand the incidence and severity of neutropenia in patients taking clozapine, and the Agency is conducting a study using the Sentinel System to better understand adherence to the monitoring requirements. All three studies are currently ongoing, and we expect the findings from these studies to be complete within the next year. The Agency intends to take appropriate regulatory action, as needed, based on its reevaluation of the Clozapine REMS.

On July 29, 2021, FDA approved modifications to the Clozapine Risk Evaluation and Mitigation Strategy (REMS) to ensure that the benefits of the drug outweigh the risk of severe neutropenia. The Clozapine REMS is a shared system REMS for all approved clozapine products. The Clozapine REMS ensures appropriate patient monitoring for and management of clozapine-induced severe neutropenia and provides a centralized system for prescribers and pharmacists in managing patient risk, regardless of which clozapine product is being used. Prior to the approval of the Clozapine REMS Program, individual clozapine manufacturers operated separate patient registries.

Beginning November 15, 2021, the new requirements will go into effect. Key changes include:

  • Pharmacies will no longer be able to use telecommunication verification (also known as the switch system) to verify safe use conditions for clozapine. The authorization to dispense clozapine can be obtained either through the contact center or online via the REMS website. 
    • Pharmacists will need to go to www.clozapinerems.com.; or call the Clozapine Contact Center to verify information and obtain a REMS dispense authorization to dispense clozapine
  • New Patient Status Form to document monitoring for all outpatients. This form must be submitted monthly.
    • Patient monitoring must still continue per the Prescribing Information.

These changes do not impact the safe use of clozapine.

Frequently Asked Questions

Q1. What is Clozapine?

A1. Clozapine is an antipsychotic drug used to help improve the symptoms of schizophrenia in patients who do not respond adequately to standard antipsychotic treatment. Symptoms of schizophrenia include hearing voices or seeing things that are not there and being suspicious or withdrawn. Clozapine may also help reduce the risk of repeated suicidal behavior in patients with schizophrenia or schizoaffective disorder.   

Because of the risk of severe neutropenia, a blood condition that can lead to severe infections, clozapine is only available through the Clozapine Risk Evaluation and Mitigation Strategy (REMS).

Q2. What is a Risk Evaluation and Mitigation Strategy (REMS)?

A2. A REMS is a drug safety program  that the U.S. Food and Drug Administration (FDA) can require for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. REMS are designed to reinforce medication use behaviors and actions that support the safe use of that medication. While all medications have labeling that informs health care stakeholders about medication risks, only a few medications require a REMS.  

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