Key Takeaways

The federal Clozapine REMS program was officially eliminated on June 13, 2025.
Mandatory enrollment, registry reporting, and dispense authorizations are no longer required.
Consistent monitoring remains a vital safety standard for all clozapine patients.
Prescribers now determine monitoring frequency with their patients based on clinical guidelines.
Removing the REMS program reduces barriers and improves patient access to treatment.

What is a REMS Program?

A Risk Evaluation and Mitigation Strategy (REMS) is a safety program the FDA can require for a medication whose benefits need specific safeguards to outweigh its risks. ¹

As of September 2026, there are 71 medications with REMS. They include medications with risk of severe side effects, risk for addiction, and those that require special training to administer. ¹

Why did Clozapine require a REMS Program?

In the 1970s, it was discovered that clozapine can cause neutropenia: a drop in a specific type of white blood cell (neutrophils) that helps fight off infections. This side effect was later determined to affect less than 1% of patients ², but after it first was identified, clozapine was withdrawn from the market by its manufacturer.

In 1989, the FDA approved usage of clozapine for “treatment-resistant schizophrenia” but it could only be prescribed along with strict, mandatory blood monitoring. The Clozapine REMS program was established to ensure that those monitoring requirements were met.

The program required special certifications for prescribers and pharmacies, and for patients to be enrolled in a shared national registry. Before a pharmacy could hand over a prescription, a doctor had to report their patient’s recent blood test results, specifically the ANC, which measures the absolute neutrophil count, into a national system. ³

Why the FDA removed the requirements

On November 19, 2024, the FDA convened a hearing to reassess the program. ² Several findings led to their decision to end it.

First, they found that the risk of neutropenia is far less than what was initially assumed when the program was created and the risk is greatest in the first several months of treatment. ⁴ At the meeting, professor of psychiatry Dr. John Kane described a research study showing that neutropenia occurred in only 0.4% of 260,000 clozapine-treated patients. ²

They also acknowledged the additional barriers to access created by the program as part of the reason that clozapine has long been prescribed well below what its evidence supports. ⁵ It’s estimated that less than 15% of people experiencing “treatment-resistant psychosis” have access to it. ⁶

Training, guidelines, and resources about clozapine treatment have greatly expanded since the REMS program was introduced. Doctors are now well aware of the risk for neutropenia and the need for monitoring.

Committee chair, Dr. James Floyd, said he arrived at the meeting expecting to vote to continue the REMS certification requirements, but he changed his mind during the meeting: “After understanding the magnitude of untreated treatment-resistant schizophrenia, it became clear to me that even this barrier was not worth the harm done.” ²

Considering each of these factors, the FDA concluded that the Clozapine REMS program was no longer necessary, ending enforcement of the program in early 2025.

Timeline: when the program started and ended

Key dates for the Clozapine REMS program.
Date	What happened
1989	Clozapine approved in the United States, with mandatory blood monitoring as a condition of approval ⁷
2015	Separate manufacturer registries consolidated into one shared Clozapine REMS. ⁸
November 19, 2024	FDA convenes a joint advisory committee. After hearing testimony from 29 public speakers, the committee votes 1–14 that ANC documentation and pharmacy verification are not necessary for safe use, and 1–14 that mandatory prescriber education is not necessary.
February 24, 2025	FDA announces enforcement discretion, meaning they would no longer require prescribers, pharmacies, and patients to report ANC results. ⁹
June 13, 2025	Clozapine REMS is formally eliminated. ⁴

What changed for families

At the November 2024 hearing, twenty-nine members of the public testified. Many of them were families who described how the REMS program had failed them.

In one of those testimonies, Joanie Martin’s story was shared. She had been living well on clozapine in Vermont for more than twenty years. Joanie earned an associate’s degree, started her own business, and was finally coming off disability. In December 2021, her pharmacy could not fill her prescription because of an issue with her paperwork. After five days, she experienced a severe relapse. She went on to lose her apartment, her business, and her independence. She was hospitalized three times that year and was back on disability. Joanie was not well enough to attend the hearing so her mother, Phyllis, read her statement to the committee. ²

This scenario wasn’t unique to Joanie. The FDA program's administrator told the committee that roughly 28% of dispense authorization requests were rejected, mostly due to a missing form. ²

Now that the program has ended, pharmacies no longer need sign-off from a national system before filling clozapine prescriptions. Delays caused by that step, and the paperwork issue that cost Joanie two decades of recovery, are gone. However, regular blood monitoring is still important.

What monitoring is still required

The following table shows the FDA-recommended absolute neutrophil count (ANC) blood monitoring schedule for clozapine.

Absolute neutrophil count testing schedule, per the FDA-approved labeling ¹⁰
Period	How often
Baseline, before the first dose	Once
Start through month 6	Weekly
Months 7 to 12	Every 2 weeks
After 12 months	Monthly

An international expert consensus published in The Lancet Psychiatry in July 2025 recommends a different schedule for ANC monitoring: weekly for the first 18 weeks, then every four weeks, with routine monitoring stopped after two years. ¹¹

The American Society of Clinical Psychopharmacology takes a similar view, suggesting label monitoring for at least the first year and shared decision-making about frequency after that. ⁶

Beyond ANC monitoring, prescribers frequently monitor heart rate, blood pressure, glucose and a variety of other indicators to effectively manage the side effects of clozapine.

Decisions about what to monitor and how often should be made between clinicians and their patients. It's vital for patients to reach out to their providers when they experience signs of infection, fever, pneumonia, and constipation while taking clozapine. ⁶

What changed for prescribers

Per the FDA drug safety communication ⁴ and the FDA REMS modification FAQ: ³

No REMS enrollment or certification.
No enrolling patients in a registry.
No submitting ANC results to the REMS.
No waiting on a dispense authorization before a pharmacy can fill a prescription.

One thing did not change. Prescribers should continue to monitor the absolute neutrophil count for their patients. ⁴ ¹⁰

For prescribers: where to find current guidance

Several health systems published their own post-REMS protocols, including the Department of Veterans Affairs ¹²:

If you’re a provider who manages clozapine and wants to talk through a specific case, our clinical team takes referrals and consults. See our provider page.

At a Glance

Topic	Details
When it ended	June 13, 2025
What ended	Registry, prescriber and pharmacy certification, patient enrollment, ANC reporting, dispense authorization
What did not end	Blood-count monitoring
Where the rules live now	The FDA-approved labeling, plus professional guidance from ASCP and the 2025 international consensus

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Common questions

Is the Clozapine REMS still required?

No. The Clozapine REMS was eliminated effective June 13, 2025. Prescribers, pharmacies and patients no longer enroll or report results to it. ⁴

Do I still need blood tests for clozapine?

Yes. Blood monitoring is still important. The FDA-approved labeling recommends a schedule, which is weekly for the first six months, every two weeks through month twelve, then monthly. ¹⁰

When did the Clozapine REMS end?

The program was formally eliminated on June 13, 2025. ⁴ The FDA had already stopped enforcing its requirements on February 24, 2025. ⁹

Do prescribers still have to be certified to prescribe clozapine?

No. Prescriber certification ended with the program. Any clinician who can prescribe medication can prescribe clozapine and is expected to monitor blood counts per the labeling.

Why did clozapine require a REMS program?

Clozapine can rarely cause severe neutropenia, a serious drop in infection-fighting white blood cells. The program was built to make sure blood counts were checked before each prescription was dispensed.

Does my pharmacy still need authorization to fill clozapine?

No. Pharmacies no longer need a REMS dispense authorization. ³ This was the most common cause of delays at the counter.

What the End of Clozapine REMS Means for Patients and Providers