New Clozapine Risk Evaluation and Mitigation Strategy (REMS) requirements Starting November 15, 2021

The FDA approved modifications to the Clozapine REMS program to ensure that the benefit of clozapine outweighs the risk of severe neutropenia that can lead to severe infections. Alterations to the clozapine REMS program will go into effect on November 15, 2021. The new REMS program will help clarify and enhance the prescribing information for clozapine, further explaining how to monitor patients for neutropenia and manage patients with severe neutropenia. The REMS program recommends that patients taking clozapine who shows signs of moderate neutropenia with an Absolute Neutrophil Count (ANC)  <1000µL should discontinue clozapine and restart once ANC levels normalize to ≥1000µL. Patients with severe neutropenia with an ANC <500µL should stop taking clozapine and only resume clozapine if the physician determines the benefit outweighs the risk.  (Clozapine and the Risk of Neutropenia: A Guide for Pharmacists: Table 1 Page 7)

The modifications to the clozapine REMS program will require physicians and pharmacies to re-certify in the clozapine REMS program and make changes to their current monitoring procedures to continue prescribing and dispensing clozapine to patients. Prescribers and pharmacies can re-certify through the clozapine REMS website.

Although patients are not required to take any action due to REMS program changes, prescribers must re-enroll or enroll their patients. Prior to enrolling patients into the REMS program, physicians must make sure their recertification into the clozapine REMS program is complete.

  • For patients currently taking clozapine, healthcare professionals will continue monitoring patients according to the current REMS requirements. However, providers can begin to re-certify and re-enroll all existing patients into the new REMS program now and must have that completed by November 15, 2021.
  • For patents starting clozapine between now and November 15, 2021, prescribers will enroll patients in both the current and new REMS programs.
  • For patients starting clozapine after November 15, 2021, prescribers will only enroll patients in the new REMS program.

The changes also make improvements to the process of submitting ANC results, which will reduce the burden on prescribers and reduce treatment interruptions for patients. Prescribers will now submit ANC documentation monthly, which is a change from daily, weekly, or biweekly documentation, depending on the patient’s monitoring frequency.

Pharmacists and authorized representatives of pharmacies should know that the current “switch” system will no longer be available.  This system allowed pharmacies to send prescription information simultaneously through (1) the Clozapine REMS Program to obtain the Pre-Dispense Authorization (PDA); and (2) their Pharmacy Management System (PMS) to adjudicate with the third party. Pharmacies will need to develop new processes and procedures to complete both transactions when dispensing clozapine.

The REMS Dispense Authorization (RDA) will replace the current Pre-Dispense Authorization (PDA). Pharmacies can access the new RDA forms through either the clozapine REMS website or by calling the REMS Contact Center. The first time a patient fills clozapine under the new REMS program, the RDA for outpatient pharmacies will verify that the pharmacy is certified, the patient is enrolled, and the patient’s treatment is not interrupted or discontinued. For subsequent fills, the RDA will verify that outpatient pharmacies are certified, the patient is enrolled, a Patient Status Form has been completed in the last 37 days, and the patient’s treatment is not interrupted or discontinued. There are no changes for inpatient pharmacies that dispense clozapine for inpatient use.

Wholesalers or distributors will have no changes to their current requirements. However, wholesalers or distributors will have to re-enroll in the Clozapine REMS by November 15, 2021 to purchase and distribute clozapine. Wholesalers and distributors will continue to verify pharmacy certification through the Clozapine REMS.




Posted: October 2021

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