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  5. Frequently Asked Questions | Clozapine REMS Modification
  1. Postmarket Drug Safety Information for Patients and Providers

Frequently Asked Questions | Clozapine REMS Modification

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On 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.

On July 29, 2021, FDA approved modifications to the Clozapine Risk Evaluation and Mitigation Strategy (REMS) to ensure that the benefits of the drug outweigh the risk of severe neutropenia. The Clozapine REMS is a shared system REMS for all approved clozapine products. The Clozapine REMS ensures appropriate patient monitoring for and management of clozapine-induced severe neutropenia and provides 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.

Beginning November 15, 2021, the new requirements will go into effect. Key changes include:

  • Pharmacies will no longer be able to use telecommunication verification (also known as the switch system) to verify safe use conditions for clozapine. The authorization to dispense clozapine can be obtained either through the contact center or online via the REMS website. 
    • Pharmacists will need to go to www.clozapinerems.com.; or call the Clozapine Contact Center to verify information and obtain a REMS dispense authorization to dispense clozapine
  • New Patient Status Form to document monitoring for all outpatients. This form must be submitted monthly.
    • Patient monitoring must still continue per the Prescribing Information.

These changes do not impact the safe use of clozapine.

Q1. What is Clozapine?

A1. Clozapine is an antipsychotic drug used to help improve the symptoms of schizophrenia in patients who do not respond adequately to standard antipsychotic treatment. Symptoms of schizophrenia include hearing voices or seeing things that are not there and being suspicious or withdrawn. Clozapine may also help reduce the risk of repeated suicidal behavior in patients with schizophrenia or schizoaffective disorder.   

Because of the risk of severe neutropenia, a blood condition that can lead to severe infections, clozapine is only available through the Clozapine Risk Evaluation and Mitigation Strategy (REMS).

Q2. What is a Risk Evaluation and Mitigation Strategy (REMS)?

A2. A REMS is a drug safety program  that the U.S. Food and Drug Administration (FDA) can require for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. REMS are designed to reinforce medication use behaviors and actions that support the safe use of that medication. While all medications have labeling that informs health care stakeholders about medication risks, only a few medications require a REMS.  

Q3. Why did the FDA approve this modification to the Clozapine REMS?

A3. The modifications were necessary to ensure safe use of clozapine while maintaining patient access.  The Clozapine Products Manufacturers Group proposed a modification to the REMS to remove the use of telecommunication verification (the switch system) for pharmacies to verify safe use conditions. After November 15, 2021 pharmacies will need to contact the REMS Program by phone or online to verify safe use conditions. The removal of the switch necessitated a modification of the REMS. Changes were also made to improve the process for a prescriber to submit absolute neutrophil count (ANC) results. Depending on the patient’s monitoring frequency, this could require daily, weekly, biweekly, or monthly documentation of the ANC. In order to reduce the burden on prescribers and minimize unintended treatment interruption for patients, the documentation of ANC will now be submitted monthly.   

Q4. What should patients know about the new requirements in the Clozapine REMS program?

A4. There are no changes to requirements for patients. Patients do not need to take any action. Patients will continue to have blood tests (ANC monitoring). Because of the significant changes in the REMS program, prescribers must re-enroll  their patients who will continue treatment with clozapine. .

Patients may talk with their prescriber and pharmacy about these change to the Clozapine REMS. For more information about this change, call the Clozapine REMS Transition Contact Center at 1-888-586-0758 or visit the Clozapine REMS website.

Q5. What actions do prescribers need to take to continue to participate in the new Clozapine REMS?

A5. Health care professionals who prescribe clozapine therapy for outpatient use and/or initiate treatment for inpatients will need to re-certify and re-enroll all patients continuing on clozapine treatment in   the Clozapine REMS program by November 15, 2021.

Re-certification of prescribers and re-enrollment of patients must be done with the revised Clozapine REMS materials. To do this, health care professionals should access the new clozapine REMS website beginning August 16, 2021:

  • Go to www.clozapinerems.com
    • Click on the link in the Important Program Update. You will be taken to the modified Clozapine REMS website.
    • Prescribers must create new login credentials.
    • Click on Log-in | Register tab. These credentials will only work on the modified Clozapine REMS.
    • Prescribers must first review the Prescriber Training, complete, and submit the Knowledge Assessment and Prescriber Enrollment Form to become re-certified
    • Then re-enroll your patients using the Patient Enrollment Form.
  • Beginning August 2, 2021, a Transition Contact Center is available at 888-586-0758 to support re-certification, re-enrollment activities and to answer questions. 

Q6. What should prescribers know about the new requirements in the Clozapine REMS program?

 A6.  Beginning November 15, 2021, prescribers will no longer need to submit ANC results according to the patient’s monitoring frequency. Instead ANC results will be submitted monthly through a new Patient Status Form. The Patient Status Form is used to document the patient’s ANC results, monitoring frequency, and appropriateness to continue treatment. Patient monitoring must continue per the Prescribing Information but the reporting of patient ANC on the Patient Status Form must be submitted monthly. 

  • Continue to monitor existing patients according to the current REMS requirements prior to the November 15, 2021 launch of the new Clozapine REMS Program. All existing patients will need to be re-enrolled in the new program by November 15, 2021.
  • Enroll all new patients starting clozapine between now and November 15, 2021 in both the current program and the new program. 
  • After November 15, 2021, enroll all new patients starting treatment with clozapine in the newly modified REMS program.

Q7. What actions do  pharmacists and authorized representatives of pharmacies need to take to continue to participate in the new Clozapine REMS?

A7. By November 15, 2021, all pharmacies must re-certify in the Clozapine REMS in order  to dispense clozapine. The authorized representative will be responsible for recertifying the pharmacy.

Re-certification of pharmacies must be done with the revised Clozapine REMS materials. In order for an individual pharmacist to re-enroll in the Clozapine REMS, the certified authorized representative will need to invite the pharmacist to enroll in the program using a valid email address. Authorized representatives should access the new Clozapine REMS website  beginning August 16, 2021:

  • Go to www.clozapinerems.com.
  • Click on the link in the Important Program Update. You will be taken to the new Clozapine REMS website.
  • Authorized representatives must create new log-in credentials.
  • Click on Log-in | Register tab. These credentials will only work on the modified Clozapine REMS website.
  • Authorized representatives must first review the Pharmacy Training, complete and submit the Knowledge Assessment and Pharmacy Enrollment form to become re-certified 

Note: Large chain pharmacies may call the Clozapine REMS Transition Contact Center at 1- 888-586-0758 if they wish to perform a bulk upload of stores and staff.  

Q8. What should pharmacists and authorized representatives of pharmacies know about the new requirements in the Clozapine REMS?

A8. Beginning November 15, 2021, the current “switch” system or pharmacy management system that is currently used as an option to verify safe use conditions for clozapine will be removed. Pharmacies that previously used the switch system may need to develop new processes and procedures to be able to continue dispensing clozapine. Pharmacists will need to go to www.clozapineREMS.com or call the Clozapine Call Center at 1-888-586-0758 to verify information and obtain a REMS dispense authorization to dispense clozapine. 

The Pre-Dispense Authorization (PDA) will be replaced by a REMS Dispense Authorization (RDA). For outpatient pharmacies, RDA of the first dispense will verify that the pharmacy is certified, patient is enrolled, and patient’s treatment is not interrupted or discontinued. RDA for subsequent dispensings will verify that that pharmacy is certified, patient is enrolled, a Patient Status Form has been completed in the last 37 days, and patient’s treatment is not interrupted or discontinued.

There are no changes to the requirements for pharmacies that dispense clozapine for inpatient use. For inpatient use, pharmacies will continue to obtain an RDA (previously called PDA) prior to the initial dispensing.

Q8. What should wholesalers/distributors know about the new requirements in the Clozapine REMS program?

A8. There are no changes to the wholesalers or distributors requirements. However, due to the significant changes to the REMS program, all wholesalers/distributors must be re-enrolled in the Clozapine REMS by November 15, 2021 in order to purchase and distribute clozapine. Wholesalers and distributors will continue to verify the pharmacy’s certification through the Clozapine REMS. The requesting pharmacy will need to be certified in the modified Clozapine REMS. Beginning August 16, 2021 wholesalers/distributors can re-enroll on the Clozapine REMS website.

Q9. When does the modified Clozapine REMS Program go into effect?

A9. The modified Clozapine REMS Program will launch on November 15, 2021. Beginning August 2, 2021, stakeholders may contact the Clozapine REMS Transition Contact Center at 1-888-586-0758 for general inquiries about the Clozapine REMS. Beginning August 16, 2021 stakeholders can re-certify and re-enroll on the new Clozapine REMS website.

To reach the new Clozapine REMS website:

 
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