Navigating the New Clozapine REMS

Bret S. Stetka, MD; Mitchell Mathis, MD


December 04, 2015

Editorial Collaboration

Medscape &

Editor's Note:
On September 15th, 2015, the US Food and Drug Administration (FDA) approved a new, shared risk evaluation and mitigation strategy (REMS) for the atypical antipsychotic medication clozapine in order to help address ongoing concerns about the association between the drug and neutropenia. The FDA announced that they would be extending the original November 23, 2015, prescriber certification deadline and the December 14, 2015, pharmacy certification deadline to help ensure that healthcare professionals have sufficient time to complete the certification process and that patient access to clozapine is maintained.

Medscape recently spoke with Mitchell Mathis, MD, director of the Division of Psychiatry Products in the Office of New Drugs at the FDA's Center for Drug Evaluation and Research (CDER/OND/DPP), about the intentions of the new REMS and its potential influence on patient care.

Medscape: What indications are clozapine currently approved by the FDA for?

Dr Mathis: Clozapine is an antipsychotic drug used to treat schizophrenia in patients whose symptoms are not controlled with standard antipsychotic treatment. It is also used to treat recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder.

Treatment with clozapine may help improve the symptoms of schizophrenia in patients who do not respond adequately to standard antipsychotic treatment. Symptoms of schizophrenia include hearing voices, seeing things that are not there, and being suspicious or withdrawn.

Clozapine may also help reduce the risk for repeated suicidal behavior in patients with schizophrenia or schizoaffective disorder.

Medscape: What is the risk addressed by this REMS?

Dr Mathis: Clozapine is associated with severe neutropenia, which can lead to serious and fatal infections. A REMS is required to ensure that the benefits of clozapine outweigh the risk for severe neutropenia.

Medscape: What was the rationale behind creating a unified clozapine REMS program? In other words, why this, and why now?

Dr Mathis: There are two main reasons for creating a unified clozapine REMS program. First, substantial changes were made to the prescribing information with regard to how to monitor for neutropenia and manage clozapine treatment on the basis of the patient's absolute neutrophil count (ANC). These labeling changes were going to cause substantial effects on how the six previous registries operated. The changes provided an opportunity to revise and consolidate the six registries at the same time that the monitoring guidelines were modified.

Second, each of six previous registries had similar requirements but subtle differences with regard to how they operated. In addition, prescribers, pharmacies, and patients were required to enroll in each one separately to be able to prescribe, dispense, or receive the specific clozapine medicine available from that manufacturer.

The shared REMS was created to reduce the burden and possible confusion related to having separate registries for individual clozapine medicines. With the unified or "shared" REMS, prescribers, pharmacies, and patients are able to enroll in a single shared program that provides access to all clozapine products regardless of the manufacturer.


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