FDA Addresses Safety Concerns for Clozapine Medicines

FDA Addresses Safety Concerns for Clozapine Medicines

SAMHSA is sharing the following announcement on behalf of the U.S. Food and Drug Administration (FDA).

FDA Modifies Monitoring for Neutropenia Associated With Schizophrenia Medicine Clozapine and Approves New Shared REMS Program for All Clozapine Medicines

The FDA has announced that it will make changes to the requirements for monitoring, prescribing, dispensing, and receiving the medicine clozapine. These changes address continuing safety concerns and current knowledge about a serious blood condition called severe neutropenia.

Clozapine is a medication prescribed for treatment-resistant schizophrenia. Its use may be recommended after more standard antipsychotic treatments fail to address symptoms or result in adverse side effects such that an effective dosage level cannot be attained. Clozapine, however, is associated with a potential serious decline in white blood cell (WBC) counts that could put an individual at considerable risk for infection. Historically, WBC counts and agranulocytosis (ANC) have been monitored in patients taking clozapine for a condition called neutropenia. Research indicates that normative ANC levels vary among racial and ethnic groups, although prescribing and monitoring guidelines are normed to ANC ranges of white/Caucasian populations. This has had a disparate impact in access to clozapine, particularly for African Americans. Although this form of neutropenia may be benign (referred to as BEN—benign ethnic neutropenia), patients with BEN are less likelythan their white counterparts to have clozapine initiated and sustained due to blood values falling into the "danger" zones.

To address current knowledge on neutropenia, the FDA has made changes to requirements for monitoring, prescribing, dispensing, and receiving the clozapine drugs. The FDA clarified and enhanced prescribing information that explains how to monitor patients for neutropenia and manage clozapine treatment. Neutropenia will now be monitored by ANC only, rather than in conjunction with the WBC. Additionally, the requirements for ANC have been 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. With the new prescribing guidelines, patients with BEN, who previously were not eligible for clozapine treatment, will now be able to receive the medicine.

The FDA also approved a new shared "risk evaluation and mitigation strategy (REMS)" that is expected to reduce the burden and possible confusion related to having separate registries for individual clozapine medicines.

Starting on October 12, 2015, prescribers and pharmacies must be certified in the Clozapine REMS Program. To be certified, prescribers and pharmacies will (1) review prescribing information and the Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers, (2) successfully pass the Knowledge Assessment for Healthcare Providers, and (3) complete and submit the one-time Clozapine REMS Prescriber Enrollment Form. SAMHSA encourages providers to get certified through the Clozapine REMS Program online or to fax completed forms to 844-404-8876.

For More Information:
Clozapine REMS Program: www.clozapinerems.com. If you have any questions, please contact the Clozapine REMS Program at 844-267-8678.