Discussion 11B #1- Heidi

The clozapine REMS program is a program that helps ensure safety by monitoring risk evaluation and
management strategies to keep patients safe due to the high risk side effects of this medication. The
indications for clozapine are for treatment resistant schizophrenia, it belongs to the CYP450 family, and
it is believed to be a D2, 5HT, alpha adrenergic, and cholinergic muscarinic receptor antagonist
(Epocrates, 2019). There are many significant side effects, and it has a Black Box Warning from the FDA
due to the risk of severe neutropenia which could result in death. Other side effects that may occur
especially initially is OH, bradycardia, syncope, seizures, or myocarditis (Epocrates, 2019).

A practitioner must be enrolled in the Clozapine REMS (risk evaluation and management strategy)
program and certified prior to prescribing clozapine per FDA requirements(What Is the Clozapine
REMS?, 2021). Also, pharmacies must be certified to dispense the medication and patients must be
enrolled in the program to receive the medication. The practitioner needs to know the patient’s baseline
ANC before starting treatment and understand that there is a condition called Benign Ethnic
Neutropenia (BEN) that can cause a person to have a baseline ANC that is lower than “normal” and
those patient will have different monitoring parameters (Clozapine and the Risk of Neutropenia, 2021).
The practitioner is required to submit the patient’s ANC results per protocol to the Clozapine REMS
system. There is a baseline level, then every week for 6 months, then every 2 weeks for 6 months, and
then monthly so long as ANC levels remain WNL for that patient (Clozapine and the Risk of Neutropenia,
2021). If the patient becomes, neutropenic and treatment must stop, the patient must have daily ANC
blood tests until safe levels return (based on individual patient status).

The patient needs to be informed to report any of the following to the provider:

Infection sign and symptoms including: fever or chills; sores or ulcers inside mouth, gums, or on skin;
wounds that take longer than normal to heal; having flu like sx; symptoms of a UTI; vaginal itching or
discharge; abdominal pain; sores in perianal area; or feeling extremely weak or tired (What Is the
Clozapine REMS?, 2021). Patients, providers, and pharmacist are expected to report any SUSPECTED
ADVERSE REACTIONS, contact the Clozapine REMS Contact Center at 1-888-586-0758 or FDA at 800-
FDA-1088 or http://www.fda.gov/medwatch (What Is the Clozapine REMS?, 2021).

References
Clozapine and the risk of neutropenia: A guide for healthcare providers. (2021). Clozapine Product
Manufacturers Group.

Epocrates. (2019). (Version 21.4.1) [Mobile app]. Apple Itunes. https://online.epocrates.com/ (Links to
an external site.)

What is the Clozapine REMS? (2021). Clozapine REMS. https://www.newclozapinerems.com/home#

(Links to an external site.)

Discussion 11B #2- Roseline

What is the Clozapine REMS program?

Clozapine is an atypical antipsychotic medication approved for treatment-resistant schizophrenia and

suicidal behavior in schizophrenia or schizoaffective disorders. Despite its therapeutic efficacy, clozapine
is associated with several adverse effects, including agranulocytosis. In late 2015, the Food and Drug
Administration updated the risk evaluation and mitigation strategy (REMS) for clozapine with new
requirements for monitoring, prescribing, and dispensing. (Curry et al., 2018)

Risk Evaluation and Mitigation Strategy (REMS) is a drug safety program that the U.S. Food and Drug
Administration (FDA) can require for certain medications with serious safety concerns to help ensure the
benefits of the medication outweigh its risks. The Clozapine REMS Program focuses on patient
monitoring for and management of clozapine-induced severe neutropenia, providing a centralized
system for prescribers and pharmacists to manage patient risk (Center for Drug Evaluation and
Research, 2021)

Beginning November 15, 2021, new US Food and Drug Administration (FDA)-approved modifications to
the Clozapine Risk Evaluation and Mitigation Strategy will go into effect. These changes hope to ensure
that the benefits of clozapine outweigh the risk of severe neutropenia.

The Clozapine REMS focuses on appropriate management and monitoring of clozapine-induced severe
neutropenia. Additionally, it provides a centralized system for prescribers and pharmacists in managing
patient risk, no matter which clozapine product is being used.
Monitoring requirement:

First 6 Months

During the first six months of treatment: Weekly ANC monitoring is required for all patients

Second 6 Months

During the second six months of treatment: Monitoring frequency can be reduced to every two weeks if
the ANC remains in the normal range (ANC greater than or equal to 1500/μL for the general population,
ANC greater than or equal to 1000/μL for patients with BEN) the trademark slogan no blood no drug

One Year

After one year of treatment: If the patient’s ANC continues to remain in the normal range, ANC
monitoring may be reduced to monthly (every 4 weeks) thereafter.

What patient information do you have to enter each week, or two weeks, or monthly?

The risk of life-threatening neutropenia necessitates frequent blood draws. The absolute neutrophil
count must be checked. Because of the significant changes in the REMS program, prescribers must re-
enroll their patients who will continue treatment with clozapine. New Patient Status Forms (PSFs) to
document monitoring for all outpatients. This form must be submitted monthly. Each month, prescribers
or their designees must use the Patient Status Form (PSF) to submit ANC results, monitoring frequency,
and a continuing treatment justification to the Clozapine REMS. PSFs will be filed with a treatment
rationale for low ANC or missing labs, or designation of a Benign Ethnic Neutropenia (BEN) or a hospice
patient, are only accepted if completed and signed by a certified prescriber.

Each Week/or two weeks/or month: Patient first and last name, DOB, REM’s patient number, zip code,
and gender

Blood Draw Date: MM / DD / YYYY Reason for missing lab1:

☐ Patient Refused ☐Clinician discretion

☐ Extrinsic factors (e.g., weather, transportation issues)

General Population Information

☐ Normal Range (≥ 1500/µL)

☐ Mild Neutropenia (1000 to 1499/µL) ☐ Moderate Neutropenia (500 to 999/µL) ☐Severe Neutropenia
(< 500/µL)

BEN patient Population

☐ Normal BEN Range (≥ 1000/µL)

☐ BEN Neutropenia (500 to 999/µL)

☐ BEN Severe Neutropenia (< 500/µL) 2

Or

ANC (per μL):

Patient treatment status: Complete this section to interrupt, discontinue, or resume treatment for this
patient. No selection indicates the patient may continue treatment. ☐ Interrupt Treatment ☐
Discontinue Treatment ☐ Resume Treatment

Can you prescribe Clozapine without this certification?

The answer is “NO” All prescribers must certify in the Clozapine Risk Evaluation and Mitigation Strategy
(REMS) program, which takes less than an hour. In the knowledge assessment for prescribers, there are
12 questions, all questions must be answered correctly to be certified. On July 29, 2021, FDA approved
modifications to the Clozapine Risk Evaluation and Mitigation Strategy to ensure that the benefits of the
drug outweigh the risk of severe neutropenia. Health care professionals who prescribe clozapine
therapy for outpatient use and/or initiate treatment for inpatients will need to re-certify and re-enroll all
patients continuing on clozapine treatment in the Clozapine REMS program by November 15, 2021.

References

Center for Drug Evaluation and Research. (2021). Frequently asked questions: Clozapine rems
modification. U.S. Food and Drug Administration. https://www.fda.gov/drugs/postmarket-drug-safety-
information-patients-and-providers/frequently-asked-questions-clozapine-rems-modification

Curry, B., Palmer, E., Mounce, C., Smith, G., & Shah, V. (2018). Assessing prescribing practices of
clozapine before and after the implementation of an updated risk evaluation and mitigation strategy.
Mental Health Clinician, 8(2), 63–67. https://doi.org/10.9740/mhc.2018.03.063

What is the Clozapine REMS? Clozapine REMS. (n.d.).

https://www.newclozapinerems.com/Public/home/Prescriber