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Approved Risk Evaluation and Mitigation Strategies (REMS)

Clozapine
Shared System REMS
REMS last update: 11/10/2021

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 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 ( PI at DailyMed , Info at Drugs@FDA ) ANDA 203039 TEVA PHARMS USA 11/25/2015 00f15108-4c15-4bf3-9665-dc32e5299006 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 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 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 prescribers submit documentation that periodic monitoring of patients is performed to identify severe neutropenia
  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

Healthcare Providers who prescribe clozapine for outpatient use and/or initiate treatment for inpatients must:

To become certified to prescribe
Before treatment initiation (first dose)
  • Counsel the patient on the risks associated with clozapine, including severe neutropenia, and the Clozapine REMS Program requirements including to report signs of infection using A Guide for Patients and Caregivers: What You Need to Know about Clozapine and Neutropenia. Provide a copy to the patient unless clinical judgment indicates that the patient’s adherence to the treatment regimen will be negatively impacted by providing the Guide. | A Guide for Patients and Caregivers: What you need to Know about Clozapine and Neutropenia |
  • Assess the patient’s absolute neutrophil count (ANC). Document and submit the ANC to the REMS program using the Patient Enrollment Form. | Patient Enrollment Form |
  • Enroll the patient in the REMS Program by completing and submitting the Patient Enrollment Form to the REMS program. | Patient Enrollment Form |
During treatment;according to the monitoring frequency in the Prescribing Information
  • Assess the patient’s ANC and monitoring frequency.
  • For patients with an ANC that falls below the acceptable range: Assess the patient’s health status for appropriateness of continuing treatment.
During treatment, monthly
  • Document and submit the ANC results, the monitoring frequency, and appropriateness for continuing treatment to the REMS program using the Patient Status Form. | Patient Status Form |
After treatment discontinuation; according to the monitoring frequency in the Prescribing Information
  • Assess the patient’s ANC. Document and submit the ANC results to the REMS program using the Patient Status Form. | Patient Status Form |

Patients who are prescribed clozapine:

Before treatment initiation
During treatment; as directed by your prescriber
  • Get a blood test to check your neutrophil count.
After treatment discontinuation; as directed by your prescriber
  • Get a blood test to check your neutrophil count.
At all times
  • Inform the prescriber if you have signs and symptoms of infection.

Pharmacies that dispense clozapine for outpatient use 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 Pharmacists. | Clozapine and Risk of Neutropenia: A Guide for Pharmacists |
  • Have the authorized representative successfully complete the Knowledge Assessment for Pharmacies and submit it to the REMS program. | Knowledge Assessment for Pharmacies |
  • Establish processes and procedures to verify an available, current ANC is within the acceptable range for patients enrolled but not authorized to receive the drug.
  • Have the authorized representative enroll in the REMS program by completing and submitting the Outpatient Pharmacy Enrollment Form to the REMS program. | Outpatient Pharmacy Enrollment Form |
  • Train all relevant staff involved in dispensing clozapine on the requirements of the REMS program using the Clozapine and the Risk of Neutropenia: A Guide for Pharmacists. | Clozapine and Risk of Neutropenia: A Guide for Pharmacists |
Before dispensing
  • Obtain authorization to dispense each prescription by contacting the REMS Program to verify that the patient is enrolled and authorized to receive drug.
  • For patients enrolled but not authorized to receive clozapine: Verify an available, current ANC is within the acceptable range through the processes and procedures established as a requirement of the REMS Program, document and submit the ANC and the prescriber’s NPI to the REMS Program and obtain authorization to dispense each prescription by contacting the REMS program to verify the patient is now authorized to receive clozapine.
  • Report dosing information to the REMS Program.
To maintain certification to dispense
At all times
  • Not distribute, transfer, loan, or sell clozapine except to certified dispensers.
  • Maintain records of staff training and that all processes and procedures are in place and are being followed.
  • Comply with audits carried out by the manufacturers or a third party acting on behalf of the manufacturers, to ensure that all processes and procedures are in place and are being followed.

Pharmacies that dispense clozapine for inpatient use 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 Pharmacists. | Clozapine and Risk of Neutropenia: A Guide for Pharmacists |
  • Have the authorized representative successfully complete the Knowledge Assessment for Pharmacies and submit it to the REMS program. | Knowledge Assessment for Pharmacies |
  • Establish processes and procedures to verify an available, current ANC is within the acceptable range for patients enrolled but not authorized to receive clozapine.
  • Have the authorized representative enroll in the REMS program by completing and submitting the Inpatient Pharmacy Enrollment Form to the REMS program. | Inpatient Pharmacy Enrollment Form |
  • Train all relevant staff involved in dispensing clozapine on the requirements of the REMS program, using the Clozapine and the Risk of Neutropenia: A Guide for Pharmacists. | Clozapine and Risk of Neutropenia: A Guide for Pharmacists |
Before dispensing,first dose
  • Obtain authorization to dispense by contacting the REMS Program to verify that the patient is enrolled and authorized to receive the drug.
  • For patients enrolled but not authorized by the REMS Program to receive the drug: Verify an available, current ANC is within acceptable range through the processes and procedures established as a requirement of the REMS Program, document and submit the ANC to the REMS Program and obtain authorization to dispense each prescription by contacting the REMS program to verify the patient is now authorized to receive clozapine.
At discharge
  • Dispense no more than a 7-days’ supply.
To maintain certification to dispense
At all times
  • Maintain records of staff training and that all processes and procedures are in place and are being followed.
  • Not distribute, transfer, loan, or sell clozapine except to certified dispensers.
  • Comply with audits carried out by the manufacturers or a third party acting on behalf of the manufacturers, to ensure that all processes and procedures are in place and are being followed.

Wholesalers-distributors 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 distribution on the requirements of the REMS program.
At all times
  • Distribute only to certified pharmacies.
  • Maintain records of drug distribution for all clozapine shipments.
  • Maintain records that all processes and procedures are in place and are being followed.
  • Comply with audits carried out by the manufacturers or a third party acting on behalf of the manufacturers, 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_2021_11_10_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_2021_11_10_ANC_Lab_Reporting_Form.pdf
Clozapine and Risk of Neutropenia: A Guide for Pharmacists (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Clozapine_and_the_Risk_of_Neutropenia_A_Guide_for_Pharmacists.pdf
Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Clozapine_and_the_Risk_of_Neutropenia_A_Guide_for_Healthcare_Providers.pdf
Drop-In Summary for Healthcare Providers (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Drop_In_Summary_for_Healthcare_Providers.pdf
Drop-In Summary for Pharmacies (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Drop_In_Summary_for_Pharmacies.pdf
Factsheet: What's Changed with the Clozapine REMS Program for Pharmacies (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Factsheet_What_Changed_with_the_Clozapine_REMS_Program_for_Pharmacies.pdf
Factsheet: What's Changed with the Clozapine REMS Program for Prescribers (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Factsheet_What_Changed_with_the_Clozapine_REMS_Program_for_Prescribers.pdf
Healthcare Professional Society Letter (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Healthcare_Professional_Society_Letter .pdf
Healthcare Provider Letter (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Healthcare_Provider_Letter .pdf
Important Program Update (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Important_Program_Update.pdf
Inpatient Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Inpatient_Pharmacy_Enrollment_Form.pdf
Knowledge Assessment for Pharmacies (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Knowledge_Assessment_for_Pharmacies .pdf
Knowledge Assessment for Prescribers (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Knowledge_Assessment_for_Prescribers .pdf
Outpatient Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Outpatient_Pharmacy_Enrollment_Form .pdf
Patient Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Patient_Enrollment_Form.pdf
Patient Status Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Patient_Status_Form .pdf
Pharmacy Letter (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Pharmacy_Letter.pdf
Pharmacy Professional Society Letter (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Pharmacy_Professional_Society_Letter.pdf
Prescriber Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Prescriber_Enrollment_Form.pdf
REMS Document (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_REMS_Document.pdf
REMS Full (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_REMS_Full.pdf
REMS Program Website Screenshots (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_REMS_Program_Website_Screenshots.pdf
Website Pop-Up Message 1 (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Website_Pop_Up_Message_1 .pdf
Website Pop-Up Message 2 (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Website_Pop_Up_Message_2.pdf
Wholesaler-Distributor Letter (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Clozapine_2021_11_10_Wholesaler_Distributor_Letter.pdf

What assessment is available to the REMS?

Assessment Plan
REMS assessment plan unavailable for posting at this time.

What updates have been made to the REMS?

Date Summary of change
11/10/2021 Modified to make changes to the hours of operations for the Clozapine REMS Contact Center.
07/29/2021 Modified to:
  1. make changes to the frequency of the submission of patient monitoring via a new Patient Status Form and make changes to the pharmacy operations to verify safe use conditions for a REMS dispense authorization
  2. revise the third goal to read from "ensuring compliance with the monitoring schedule for absolute neutrophil count (ANC) prior to dispensing clozapine" to "ensuring prescribers submit documentation that periodic monitoring of patients is performed to identify severe neutropenia"
02/18/2021 Modified to:
  1. remove reference to Fazaclo (clozapine) and Jazz Pharmaceuticals Inc. from the following materials:
    1. Clozapine and Risk of Neutropenia: A Guide for Healthcare Providers
    2. Clozapine REMS Website
  2. add a previously approved generic formulation for orally disintegrating tablet produced by Teva (ANDA203039) to the generic products table on the REMS website
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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