The .gov means it's official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you're on a federal government site.
The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.
The goal of the Clozapine REMS Program is to mitigate the risk of severe neutropenia associated with the use of clozapine by:
Educating prescribers and pharmacists about the risk of severe neutropenia and appropriate monitoring requirements.
Informing patients about the risk of severe neutropenia and appropriate monitoring requirements.
Ensuring prescribers submit documentation that periodic monitoring of patients is performed to identify severe neutropenia
Ensuring the prescriber documents a risk-benefit assessment when ANC falls below the acceptable range as described in the Prescribing Information.
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.
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 |
Be enrolled in the REMS Program. Enrollment information will be provided to
the REMS Program.
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 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 |
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.
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 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 |
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.
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.
This webpage provides REMS assessment plan measures, metrics, and indicators for drug and biological products with a REMS. The REMS assessment plan measures, metrics, and indicators are part of the overall REMS assessment plan used by FDA to evaluate the performance of a REMS and are included in FDA approval letters. The current REMS assessment plan measures, metrics, and indicators are extracted from regulatory letters that contain REMS information, including FDA approval letters, and posted here as they become available.
What updates have been made to the REMS?
Date
Summary of change
09/29/2023
Updates to reflect a change in application ownership
11/10/2021
Modified to make changes to the hours of operations for the Clozapine REMS Contact Center.
07/29/2021
Modified to:
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
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:
remove reference to Fazaclo (clozapine) and Jazz Pharmaceuticals Inc. from the following materials:
Clozapine and Risk of Neutropenia: A Guide for Healthcare Providers
Clozapine REMS Website
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.
