FDA: Prescribers must certify, enroll outpatients in new clozapine REMS by Nov. 15
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The FDA can require a safety program called a Risk Evaluation and Mitigation Strategy, or REMS, for a medication with serious safety concerns to ensure the benefits outweigh the risks. An REMS is designed to reinforce behaviors and actions that support safe use of that medication to mitigate a specific risk.
Clozapine, which is marketed as Clozaril and Versacloz and approved generics, is used to treat schizophrenia after other treatments have failed. It is also used to reduce the risk for suicidal behavior in patients with schizophrenia or similar mental health disorders, but \ can cause severe neutropenia, or an unusually low number of neutrophils (a type of white blood cell), which can lead to serious and even fatal infections. Because of these risks, the FDA requires a REMS for clozapine medications.
The goal of the Clozapine REMS is to mitigate the risk of severe neutropenia associated with the use of the medication by:
- Educating prescribers and pharmacists and informing patients about the risk of severe neutropenia and appropriate monitoring requirements
- Ensuring prescribers provide documentation that appropriate patient monitoring is performed to identify severe neutropenia and conduct a benefit-risk assessment when absolute neutrophil count (ANC) falls below the acceptable range as described in the Prescribing Information
Changing program requirements
Some Clozapine REMS requirements are changing due to a recently approved modification, and these requirements will go into effect Nov. 15. As part of those changes, the Clozapine REMS will be implemented on a revised REMS platform.
In the revised REMS program, the frequency of patient monitoring remains the same as described in the labeling and based on patient need; however, the frequency of documenting the monitoring has changed. Health care providers or their designee(s) will no longer need to submit ANC results according to the patient’s monitoring frequency but instead must submit a Patient Status Form (PSF) every month for each of their outpatients on clozapine. This form documents the patient’s ANC results; monitoring frequency; any adverse event(s) the patient experiences due to clozapine-induced neutropenia; and the appropriateness of continuing treatment with clozapine.
Health care providers or their designee must submit this form monthly for the pharmacist to be able to dispense clozapine. The first PSF is due no later than 30 days after the program is implemented on Nov. 15. If the PSF is not submitted 31 days after the previous month’s submission, the prescriber will be reminded that the form is overdue. If the PSF is not submitted by day 37, the patient will not be able to receive clozapine from the pharmacy until a form is received.
If this occurs, to prevent treatment disruption, the pharmacist can request a dispense rationale to provide the patient with clozapine. To request a dispense rationale, the pharmacist must have a current (within the last 30 days) ANC within the acceptable range. The dispense rationale is limited to three per patient per year.
There are no changes to the requirements for prescribers in an inpatient setting. As with the current REMS, if a patient starts clozapine therapy as an inpatient, a certified prescriber must enroll the patient in the REMS. If a patient is continuing clozapine and is admitted as an inpatient, the inpatient prescriber is not required to become certified.
Prescribers should continue to use only the current program for patient monitoring until Nov. 15 for patients already enrolled in the REMS.
All new patients starting clozapine between now and Nov. 15 should be enrolled in both the current program and the new program; however, their monitoring will only be done in the current program until Nov. 15.
More information about the changes in the clozapine REMS is available on the factsheet, “What’s Changed in the Clozapine REMS for Prescribers?”
Actions prescribers and designees must take
To ensure there are no lapses in treatment, prescribers and their designees will need to certify in the revised Clozapine REMS program and enroll each patient continuing outpatient clozapine treatment as soon as possible but no later than by Nov. 15. As with the current REMS, if a patient is being started on clozapine therapy, a certified prescriber must enroll the patient in the REMS.
Prescribers can certify and enroll their patients on the Clozapine REMS website under Important Program Update and follow the link to the revised REMS website. This website has the materials that prescribers and their designees will need to certify and enroll patients. The website also includes training for prescribers and pharmacists, enrollment forms, FAQs and resources for prescribers and pharmacies.
To certify in the REMS program, prescribers must take the revised training, complete the knowledge assessment, and complete a new enrollment form.