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.
November 2, 2022 - FDA is temporarily exercising additional enforce discretion to prevent interruption of treatment for patients. For more information, please see the updated CDER Statement.
Information on Clozapine
Clozapine (marketed as Clozaril, Fazaclo ODT, Versacloz and generics) is an antipsychotic medicine used to treat schizophrenia in patients whose symptoms are not controlled with standard antipsychotic drugs. Clozapine is also used in patients with recurrent suicidal behavior associated with schizophrenia or schizoaffective disorder.
While clozapine is beneficial for some patients, there are risks associated with this drug. Specifically, clozapine can decrease the number of neutrophils, a type of white blood cell, that function in the body to fight off infections. When neutrophils are significantly decreased, severe neutropenia may result and the body may become prone to infections. For this reason, patients taking clozapine need to have their absolute neutrophil count (ANC) monitored on a regular basis. This monitoring requirement serves as the basis for the Clozapine Risk Evaluation and Mitigation Strategy (REMS).
Clozapine REMS Program
The Clozapine REMS Programwas approved in September 2015 and is a “shared-system” program, meaning that it includes all clozapine medicines approved by the Food and Drug Administration (FDA). The Clozapine REMS Program ensures optimal patient monitoring for and management of clozapine-induced severe neutropenia, providing 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.
In response to implementation challenges identified following the approval of the Clozapine REMS Program, the FDA announced, in November 2015, that the deadlines for certification of prescribers and pharmacies would be extended to help ensure that health care professionals had sufficient time to complete certification and to ensure patient access to clozapine was maintained.
We believe that most of the issues identified to date have been resolved. If prescribers and pharmacies experience problems while attempting to become certified, they should contact the Clozapine REMS Call Center at 844-267-8678.
In an effort to provide timely clozapine information to prescribers, pharmacies, patients, and distributors, the FDA will post any related updates on clozapine and the Clozapine REMS Program on this page.
- FDA Prescriber Outreach Presentation - August 18
- FDA Pharmacy Outreach Presentation - August 19
- CPMG FDA Prescriber Professional Society Meeting - August 18
- CPMG FDA Pharmacy Professional Society Meeting - August 19
- Frequently Asked Questions | Clozapine REMS Modification
- CDER Statements: The Clozapine Risk Evaluation and Mitigation Strategy (REMS) Program Modification will go live on February 28, 2019, 1/16/19, 12/16/16, 11/19/15, 11/13/15, and 10/20/15.
- FDA Drug Safety Communication: FDA modifies monitoring for neutropenia associated with schizophrenia medicine clozapine; approves new shared REMS program for all clozapine medicines, 9/15/15
- Clozapine REMS website
- Clozapine REMS information on the FDA website
If you have questions or concerns about the Clozapine REMS Program or its website please contact FDA at firstname.lastname@example.org, 1-855-543-3784 or 301-796-3400.