Approved Risk Evaluation and Mitigation Strategies (REMS)

Clozapine
Shared System REMS
REMS last update: 11/12/2019

What medicines are included in the REMS?

Product Name Application Number Application Holder Added to REMS DailyMed Link FDA Link
Clozaril (clozapine) ( PI at DailyMed , Info at Drugs@FDA ) NDA 019758 HERITAGE LIFE 09/15/2015 5f0c6f5f-b906-4c8f-8580-3939a476a1c1 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=019758
Fazaclo ODT (clozapine) ( PI at DailyMed , Info at Drugs@FDA ) NDA 021590 JAZZ 09/15/2015 b7b7541a-1fe4-4b11-b6b7-68fb5510faa4 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=021590
Versacloz (clozapine) ( PI at DailyMed , Info at Drugs@FDA ) NDA 203479 TASMAN PHARMA 09/15/2015 693cb9d4-39db-4ecf-9eae-b01f06f8d5d1 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=203479
clozapine ( PI at DailyMed , Info at Drugs@FDA ) ANDA 203807 MAYNE PHARMA 09/17/2015 339eedf1-6c19-46e0-be8f-3a58ea4d49d3 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=203807
clozapine ( PI at DailyMed , Info at Drugs@FDA ) ANDA 206433 AUROBINDO PHARMA LTD 11/29/2016 5021d643-32d2-4167-b5d8-90870e68a787 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=206433
clozapine ( PI at DailyMed , Info at Drugs@FDA ) ANDA 090308 BARR LABS INC 11/25/2015 6fccf4f7-2e30-4272-9800-225aaef20584 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=090308
clozapine ( Info at Drugs@FDA ) ANDA 203039 TEVA PHARMS USA 11/25/2015 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=203039
clozapine ( PI at DailyMed , Info at Drugs@FDA ) ANDA 202873 ACCORD HLTHCARE 11/25/2015 25c0c6d5-f7b0-48e4-e054-00144ff8d46c http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=202873
clozapine ( PI at DailyMed , Info at Drugs@FDA ) ANDA 075713 SUN PHARM INDS INC 09/15/2015 53bdb79c-c4cf-4818-b1f0-225e67a14536 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=075713
clozapine ( PI at DailyMed , Info at Drugs@FDA ) ANDA 201824 MYLAN 09/15/2015 9ae4b8e4-d8b1-4f01-bb4c-cd1cea90b219 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=201824
clozapine ( PI at DailyMed , Info at Drugs@FDA ) ANDA 075417 MYLAN 09/15/2015 883b5d43-0339-7dc1-f775-93791fb9b978 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=075417
clozapine ( PI at DailyMed , Info at Drugs@FDA ) ANDA 074949 IVAX SUB TEVA PHARMS 09/15/2015 47c4897c-ee95-4eaf-adbc-84130d021d2d http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=074949
clozapine ( PI at DailyMed , Info at Drugs@FDA ) ANDA 076809 IVAX SUB TEVA PHARMS 09/15/2015 47c4897c-ee95-4eaf-adbc-84130d021d2d http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=076809

What is the purpose of the REMS?

The goal of the Clozapine REMS Program is to mitigate the risk of severe neutropenia associated with the use of clozapine by:

  1. Educating prescribers and pharmacists about the risk of severe neutropenia and appropriate monitoring requirements.
  2. Informing patients about the risk of severe neutropenia and appropriate monitoring requirements.
  3. Ensuring compliance with the monitoring schedule for absolute neutrophil count (ANC) prior to dispensing clozapine.
  4. Ensuring the prescriber documents a risk-benefit assessment when ANC falls below the acceptable range as described in the Prescribing Information.
  5. Establishing long-term safety and safe use of clozapine by enrolling all patients who receive clozapine in the registry.

What do participants need to know?

Below is a general overview of the REMS for all REMS participants (e.g., patients, pharmacies, and healthcare providers). See the application holder(s) REMS Website or the approved REMS materials for more information.

View application holder(s) REMS Website See Disclaimer page regarding links to external sites

Inpatient pharmacies that dispense clozapine must

To become certified to dispense
  • Designate an authorized representative to carry out the certification process and oversee implementation and compliance with the REMS Program on behalf of the pharmacy.
  • Have the authorized representative review Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers.
  • Have the authorized representative successfully complete the Knowledge Assessment for Healthcare Providers and submit it to the REMS Program.
  • Train all relevant staff involved in the dispensing of clozapine on the REMS program requirements using Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers.
  • Have all pharmacists review the Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers.
  • Have all pharmacists successfully complete the Knowledge Assessment for Healthcare Providers and submit it to the authorized representative.
  • Establish processes and procedures to verify the patient is enrolled.
  • Establish processes and procedures to verify the patient’s absolute neutrophil count (ANC) is current.
  • Establish processes and procedures to verify the patient’s ANC is within an acceptable range described in the Prescribing Information or the prescriber has authorized the continuation of clozapine treatment for patients with an ANC that falls below the acceptable range when the prescriber determines the benefits exceed the risks of developing severe neutropenia prior to dispensing.
  • Have the authorized representative enroll in the REMS Program by completing and submitting the Clozapine REMS Inpatient Pharmacy Enrollment Form.
Before dispensing
  • Verify that the patient is enrolled by performing an Eligibility Check from the REMS Program by accessing the REMS Program Website or contacting the REMS Program Contact Center.
  • Obtain a current ANC by accessing the REMS Program Website, contacting the REMS Program Contact Center, or by accessing the inpatient medical record.
  • Verify that the ANC is within the acceptable range described in the Prescribing Information or that the prescriber has authorized clozapine treatment for patients with an ANC that falls below the acceptable range when the prescriber determines the benefits outweigh the risks of developing severe neutropenia. At/upon discharge
At/upon discharge
  • Dispense no more than a 7-day supply.
To maintain certification to dispense, every 2 years
  • Renew certification in the REMS Program.
At all times
  • Maintain records of staff training.
  • Maintain records of all processes and procedures are in place and are being followed
  • Comply with audits carried out by the applicants or third party acting on behalf of the applicants to ensure that all processes and procedures are in place and are being followed.

Healthcare Providers who prescribe clozapine products for outpatient use or to a patient not yet enrolled in the program must

To be able to prescribe
  • Review the drug's Prescribing Information
  • Review Clozapine and Risk of Neutropenia: A Guide for Healthcare Providers
  • Successfully complete the Knowledge Assessment for Healthcare Providers and submit it to the REMS Program.
  • Enroll in the REMS Program by completing the Prescriber Enrollment Form and submitting it to the REMS Program.
Before the first prescription
  • Counsel the patient on the risks associated with clozapine including severe neutropenia and the REMS program requirements using What You Need to Know about Clozapine and Neutropenia: A Guide for Patients and Caregivers.
  • Provide the patient with What You Need to Know about Clozapine and Neutropenia: A Guide for Patients and Caregivers unless clinical judgment indicates that the patient’s adherence to the treatment regimen will be negatively impacted
  • Assess the patient’s absolute neutrophil count (ANC). Document and submit the results to the REMS program.
  • Enroll the patient by completing and submitting the Patient Enrollment Form. Retain a completed copy in the patient’s record.
During treatment; at specific intervals, according to the Prescribing Information
  • Assess the patient’s ANC. Document and submit the results to the REMS program.
  • For patients with an ANC that falls below the acceptable range described in the Prescribing Information: assess the patient’s benefits of continuing treatment with the risks of developing severe neutropenia.
  • For patients whose continuing treatment benefit exceeds the risk of developing severe neutropenia: document and submit the authorization to continue treatment to the REMS program.
  • Verify the patient monitoring frequency on file with the REMS Program is aligned with the patient’s monitoring frequency as described in the Prescribing Information.

Wholesalers that distribute clozapine must

To be able to distribute
  • Establish processes and procedures to ensure that the drug is distributed only to certified pharmacies.
  • Train all relevant staff involved in distributing on the REMS program requirements.
At all times
  • Maintain records of appropriate documentation.
  • Provide distribution data to the appropriate application holder.
  • Comply with audits carried out by the applicants or third party acting on behalf of the applicants to ensure that all processes and procedures are in place and are being followed.

Outpatient Pharmacies that support electronic telecommunication verification and that dispense clozapine must

To become certified to dispense
  • Designate an authorized representative to carry out the certification process and oversee implementation and compliance with the REMS program on behalf of the pharmacy.
  • Have the authorized representative review Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers.
  • Have the authorized representative successfully complete the Knowledge Assessment for Healthcare Providers and submit it to the REMS Program.
  • Train all relevant staff involved in the dispensing of clozapine on the REMS program requirements using Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers.
  • Verify the pharmacy enables its pharmacy management system to support communication with the REMS Program system using established telecommunication standards and runs the standardized validation test transaction(s) to validate the system enhancements.
  • Have the authorized representative enroll in the REMS Program by completing and submitting the appropriate enrollment form: Clozapine REMS Pharmacy Enrollment Form or Clozapine REMS Chain Headquarters Pharmacy Enrollment Form.
Before dispensing
  • Obtain authorization to dispense each prescription by contacting the REMS program through your pharmacy management system to: verify the prescriber is certified in the REMS Program, verify the patient is enrolled in the REMS Program, verify the ANC is current (within 7 days of the Predispense Authorization transaction date for weekly monitoring, 15 days for every two weeks monitoring and 31 days for monthly monitoring), verify the ANC is within the acceptable range described in the Prescribing Information, or that a certified prescriber has authorized clozapine treatment for patients with an ANC that falls below the acceptable range when the prescriber determines the benefits outweigh the risks of developing severe neutropenia, and report dosing information for each clozapine prescription/fill to the REMS Program.
To maintain certification to dispense, every 2 years
  • Renew certification in the REMS Program
At all times
  • Maintain records of staff training.
  • Maintain records of all processes and procedures are in place and are being followed.
  • Comply with audits carried out by the applications or third party acting on behalf of the applicants to ensure that all processes and procedures are in place and are being followed.

Patients who are prescribed clozapine

Before the first prescription
  • Get a blood test.
  • Receive counseling from the prescriber on the risks of clozapine and the REMS program requirements using What You Need to Know about Clozapine and Neutropenia: A Guide for Patients and Caregivers.
During treatment; At specified intervals, according to the prescriber
  • Get a blood test

Outpatient pharmacies that do NOT support electronic telecommunication verification and that dispense clozapine must:

To become certified to dispense
  • Designate an authorized representative to carry out the certification process and oversee implementation and compliance with the REMS Program on behalf of the pharmacy.
  • Have the authorized representative review Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers.
  • Have the authorized representative complete the Knowledge Assessment for Healthcare Providers and submit the successfully completed knowledge assessment to the application holder.
  • Train all relevant staff involved in the dispensing of clozapine on the REMS program requirements using Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers.
  • Have all pharmacists review Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers.
  • Have all pharmacists successfully complete the Knowledge Assessment for Healthcare Providers and submit it to the authorized representative.
  • Have the authorized representative enroll in the REMS Program by completing and submitting the appropriate enrollment form: Clozapine REMS Pharmacy Enrollment Form or Clozapine REMS Chain Headquarters Pharmacy Enrollment Form.
Before dispensing
  • Obtain authorization to dispense each prescription using the Clozapine REMS Program website or by contacting the call center to: verify the prescriber is certified in the REMS Program, verify the patient is enrolled in the REMS Program, verify the ANC is current (within 7 days of the Predispense Authorization transaction for weekly monitoring, 15 days for every two week monitoring and 31 days for monthly monitoring), verify the ANC is within the acceptable range described in the Prescribing Information, or that a certified prescriber has authorized clozapine treatment for patients with an ANC that falls below the acceptable range when the prescriber determines the benefits outweigh the risks of developing severe neutropenia, and report dosing information for each clozapine prescription/fill to the REM Program.
To maintain certification to dispense, every 2 years
  • Renew certification in the REMS Program.
At all times
  • Maintain records of staff training.
  • Maintain records of all processes and procedures are in place and are being followed.
  • Comply with audits carried out by the applicants or third party acting on behalf of the applicants to ensure that all processes and procedures are in place and are being followed.

View additional drug-specific postmarket safety information from the FDA

What materials are included in the REMS?

The REMS includes a REMS Document. In addition, the REMS includes the following materials intended for patients and healthcare providers.

Material Name Material Name Link
A Guide for Patients and Caregivers: What You Need to Know about Clozapine and Neutropenia (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2019_11_12_A_Guide_for_Patients_and_Caregivers_What_You_Need_to_Know_about_Clozapine_and_Neutropenia.pdf
ANC Lab Reporting Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2019_11_12_ANC_Lab_Reporting_Form.pdf
Chain Headquarters Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2019_11_12_Chain_Headquarters_Pharmacy_Enrollment_Form.pdf
Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2019_11_12_Clozapine_and_the_Risk_of_Neutropenia_A_Guide_for_Healthcare_Providers.pdf
Inpatient Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2019_11_12_Inpatient_Pharmacy_Enrollment_Form.pdf
Knowledge Assessment for Healthcare Providers (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2019_11_12_Knowledge_Assessment_for_Healthcare_Providers.pdf
Outpatient Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2019_11_12_Outpatient_Pharmacy_Enrollment_Form.pdf
Patient Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2019_11_12_Patient_Enrollment_Form.pdf
Prescriber Designee Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2019_11_12_Prescriber_Designee_Enrollment_Form.pdf
Prescriber Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2019_11_12_Prescriber_Enrollment_Form.pdf
REMS Document (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2019_11_12_REMS_Document.pdf
REMS Full (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2019_11_12_REMS_Full.pdf
REMS Program Website Screenshots (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2019_11_12_REMS_Program_Website_Screenshots.pdf

What updates have been made to the REMS?

Date Summary of change
11/12/2019 Revised to reflect editorial changes.
01/16/2019 Modified to incorporate the addition of educational materials, changes to the inpatient prescriber certification requirements and patient monitoring, and initiating the operational restrictions for prescriber and pharmacy certification.
09/15/2015 Approval of the REMS.

Disclaimer: This webpage provides general information about REMS programs to various REMS participants (e.g., patients, pharmacies, and healthcare providers). The summary information provided herein is not comprehensive and may not include all of the information relevant to REMS participants. This webpage does not constitute a replacement, modification, or revision of the approved REMS document, including any appended REMS materials. Refer to the approved REMS document for complete information on the REMS requirements for each approved application.

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