Approved Risk Evaluation and Mitigation Strategies (REMS)

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Clozapine
Shared System REMS
REMS last update: 09/15/2015

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 setid=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 PHARMS III 09/15/2015 setid=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 setid=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 setid=339eedf1-6c19-46e0-be8f-3a58ea4d49d3 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=203807
clozapine ( Info at Drugs@FDA ) ANDA 090308 BARR LABS INC 11/25/2015 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 setid=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 setid=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 PHARMS INC 09/15/2015 setid=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 setid=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 setid=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 setid=47c4897c-ee95-4eaf-adbc-84130d021d2d http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=076809
clozapine ( PI at DailyMed , Info at Drugs@FDA ) ANDA 206433 AUROBINDO PHARMA LTD 11/29/2016 setid=5021d643-32d2-4167-b5d8-90870e68a787 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=206433

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

Healthcare Providers who prescribe clozapine products must

To be able to prescribe
Before the first prescription
At specified intervals, according to the Prescribing Information for a clozapine product, during treatment
  • Assess the patient’s ANC. Document and submit the results to the REMS program via the online system, by fax, or calling the contact center.
  • 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.

Patients who are prescribed clozapine shared system products

Before the first prescription
At specified intervals, according to the prescriber, during treatment
  • Get a blood test.

Outpatient pharmacies that support electronic telecommunication verification and that dispense clozapine shared system products must

To be able to dispense
  • Designate an authorized representative to carry out the certification process on behalf of the pharmacy.
  • Have the authorized representative review Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers. | 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. | Knowledge Assessment for Healthcare Providers |
  • 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. | Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers |
  • Establish processes and procedures to verify the prescriber is certified and the patient is enrolled.
  • Establish processes and procedures to verify the patient’s absolute neutrophil count (ANC) is current (within 7 calendar days of the blood draw).
  • 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.
  • Establish processes and procedures to report dosing information for each clozapine prescription/fill to the REMS program.
  • 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 by completing and submitting the appropriate enrollment form: Clozapine REMS Pharmacy Enrollment Form or Clozapine REMS Chain Headquarters Pharmacy Enrollment Form. | Pharmacy Enrollment Form | | Chain Headquarters Pharmacy Enrollment Form |
Before dispensing
  • Obtain authorization to dispense by processing the prescription through the pharmacy management system.
At all times
  • Maintain records of staff training.
  • Maintain records of all processes and procedures are in place and are being followed. Maintain records of all processes and procedures are in place and are being followed.
  • Cooperate with audits carried out by the application holder to ensure that all processes and procedures are in place and are being followed.

Outpatient pharmacies that do NOT support electronic telecommunication verification and that dispense clozapine shared system products must

To be able to dispense
  • Designate an authorized representative to carry out the certification process on behalf of the pharmacy.
  • Have the authorized representative review Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers. | 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. | Knowledge Assessment for Healthcare Providers |
  • 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. | Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers |
  • All pharmacists: review Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers. | Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers |
  • All pharmacists: complete the Knowledge Assessment for Healthcare Providers and submit the successfully completed knowledge assessment to the authorized representative. | Knowledge Assessment for Healthcare Providers |
  • Establish processes and procedures to verify the prescriber is certified and the patient is enrolled.
  • Establish processes and procedures to verify the patient’s absolute neutrophil count (ANC) is current (within 7 calendar days of the blood draw).
  • 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.
  • Establish processes and procedures to report dosing information for each clozapine prescription/fill to the REMS program.
  • Have the authorized representative enroll in the REMS by completing and submitting the appropriate enrollment form: Clozapine REMS Pharmacy Enrollment Form or Clozapine REMS Chain Headquarters Pharmacy Enrollment Form. | Pharmacy Enrollment Form | | Chain Headquarters Pharmacy Enrollment Form |
Before dispensing
  • Obtain authorization to dispense using the Clozapine REMS Program website or by contacting the call center.
At all times
  • Maintain records of staff training.
  • Maintain records of all processes and procedures are in place and are being followed.
  • Cooperate with audits carried out by the application holder to ensure that all processes and procedures are in place and are being followed.

Inpatient pharmacies that dispense clozapine shared system products must

To be able to dispense
  • Designate an authorized representative to carry out the certification process on behalf of the pharmacy.
  • Have the authorized representative review Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers. | 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. | Knowledge Assessment for Healthcare Providers |
  • 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. | Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers |
  • All pharmacists: review the Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers. | Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers |
  • All pharmacists: complete the Knowledge Assessment for Healthcare Providers and submit the successfully completed knowledge assessment to the authorized representative. | Knowledge Assessment for Healthcare Providers |
  • Establish processes and procedures to verify the patient’s absolute neutrophil count (ANC) is current (within 7 calendar days of the blood draw).
  • 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.
  • Establish processes and procedures to report dosing information for each clozapine prescription/fill to the REMS program.
  • Have the authorized representative enroll in the REMS by completing and submitting the Clozapine REMS Pharmacy Enrollment Form. | Pharmacy Enrollment Form |
Before dispensing
  • Verify the prescriber is certified and the patient is enrolled by contacting the Clozapine REMS Program website or by contacting the call center.
  • Verify that ANC is current and within the 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 using the Clozapine REMS Program website, by contacting the call center, or checking the patient’s medical record.
At all times
  • Maintain records of staff training.
  • Maintain records of all processes and procedures are in place and are being followed.
  • Cooperate with audits carried out by the application holder to ensure that all processes and procedures are in place and are being followed.

Wholesalers that distribute clozapine shared system products must

To be able to distribute
  • Establish processes and procedures to verify that the drug is distributed only to certified pharmacies.
  • Train all relevant staff involved in on the REMS program requirements.
At all times
  • Maintain records of appropriate documentation.
  • Provide distribution data to the appropriate application holder.
  • Cooperate with audits carried out by the application holder 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
ANC Lab Reporting Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/clozapine_2015-09-15_ANC_Lab_Reporting_Form.pdf
Chain Headquarters Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/clozapine_2015-09-15_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_2015-09-15_A_Guide_for_Healthcare_Providers.pdf
Knowledge Assessment for Healthcare Providers (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/clozapine_2015-09-15_Knowledge_Assessment_for_Healthcare_Providers.pdf
Patient Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/clozapine_2015-09-15_Patient_Enrollment_Form.pdf
Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/clozapine_2015-09-15_Pharmacy_Enrollment_Form.pdf
Prescriber Designee Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/clozapine_2015-09-15_Prescriber_Designee_Enrollment_Form.pdf
Prescriber Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/clozapine_2015-09-15_Prescriber_Enrollment_Form.pdf
REMS document (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/clozapine_2015-09-15_REMS_document.pdf
REMS full (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/clozapine_2015-09-15_REMS_full.pdf
REMS Program website screenshot (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/clozapine_2015-09-15_REMS_Program_website.pdf
What You Need to Know about Clozapine and Neutropenia: A Guide for Patients and Caregivers (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/clozapine_2015-09-15_Guide_for_Patients_and_Caregivers.pdf

What updates have been made to the REMS?

Date Summary of change
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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