FDA Drug Safety Communication

The U.S. Food and Drug Administration (FDA) is making changes to the requirements for monitoring, prescribing, dispensing, and receiving the schizophrenia medicine clozapine, to address continuing safety concerns and current knowledge about a serious blood condition called severe neutropenia. Severe neutropenia is a dangerously low number of neutrophils, white blood cells that help fight infections. Severe neutropenia can be life-threatening.

Treatment with clozapine may improve the symptoms of schizophrenia in patients who do not respond adequately to standard antipsychotic treatments. Symptoms of schizophrenia include hearing voices, seeing things that are not there, and being suspicious or withdrawn. Clozapine is also effective in reducing the risk of repeated suicidal behavior in patients with schizophrenia or schizoaffective disorder. We previously communicated safety information associated with clozapine in February 2011.

There are two parts to the changes in the requirements for treating patients with clozapine. First, we have clarified and enhanced the prescribing information for clozapine that explains how to monitor patients for neutropenia and manage clozapine treatment. Second, we approved a new, shared risk evaluation and mitigation strategy (REMS) called the Clozapine REMS Program. The revised prescribing information and the Clozapine REMS Program will improve monitoring and management of patients with severe neutropenia. The shared REMS is also expected to reduce the burden and possible confusion related to having separate registries for individual clozapine medicines. The requirements to monitor, prescribe, dispense, and receive all clozapine medicines are now incorporated into the Clozapine REMS Program.

The Clozapine REMS Program replaces the six existing clozapine registries maintained by individual clozapine manufacturers. The shared REMS requires prescribers, pharmacies, and patients to enroll in a single centralized program. Patients who are currently treated with clozapine will be automatically transferred to the Clozapine REMS Program. In order to prescribe and dispense clozapine, prescribers and pharmacies will be required to be certified in the Clozapine REMS Program according to a specific transition schedule starting October 12, 2015.

The monitoring recommendations for neutropenia caused by clozapine treatment have changed. Clozapine can decrease the number of neutrophils in the blood, in some cases causing severe neutropenia. As described in the revised clozapine prescribing information, and in the Clozapine REMS Program, neutropenia will be monitored by the absolute neutrophil count (ANC) only, rather than in conjunction with the white blood cell count. Moreover, in the Clozapine REMS Program, the requirements for ANC are being modified so that patients will be able to continue on clozapine treatment with a lower ANC, a change that will allow continued treatment for a greater number of patients. In addition, patients with benign ethnic neutropenia (BEN), who previously were not eligible for clozapine treatment, will now be able to receive the medicine. The revised prescribing information facilitates prescribers' ability to make individualized treatment decisions if they determine that the risk of psychiatric illness is greater than the risk of recurrent severe neutropenia, especially in patients for whom clozapine may be the antipsychotic of last resort.

View the full FDA Drug Safety Communication on FDA.gov