Clozapine REMS Discontinued: The Blood Test Schedule That Still Applies

Creator: Ryan S. Sultan, MD
Published: 2026-11-12

By Ryan S. Sultan, MD
Psychiatrist · Columbia University Irving Medical Center
Published November 12, 2026 · 6-minute read

The FDA removed the clozapine REMS program effective June 13, 2025. Pharmacies no longer need a reported blood count before they dispense clozapine, and prescribers, pharmacies, and patients no longer enroll in a registry.¹ The blood tests themselves remain in the prescribing information: weekly for the first 6 months, every 2 weeks through month 12, and monthly after that.³

The registry is gone and the blood tests stay. The FDA was explicit that the risk of severe neutropenia remains and that prescribers should keep monitoring the absolute neutrophil count (ANC) on the label's schedule.^{1, 2}

What the REMS required, and what ended

REMS stands for Risk Evaluation and Mitigation Strategy. For clozapine it was a restricted distribution program. Prescribers, pharmacies, and patients had to be enrolled, and an ANC result had to be reported before a pharmacy could dispense.¹ A missed lab draw or a reporting error could leave someone without the one medication that was working.

It ended in two steps. On February 24, 2025, the FDA stopped expecting participation in the program or ANC reporting before dispensing. The program was formally removed effective June 13, 2025.^{2, 1} The agency concluded that the label, with a new Medication Guide, is enough to manage the risk, and that dropping the program should improve access.¹

The blood test schedule that still applies

The June 2025 Clozaril label no longer mentions the REMS. The monitoring schedule remains in it.³

ANC monitoring for patients without benign ethnic neutropenia
ANC result	What the label recommends
1,500/µL or higher (normal)	Continue. Test weekly from day 1 to month 6, every 2 weeks from month 7 to month 12, and monthly from month 13 on
1,000 to 1,499/µL (mild neutropenia)	Confirm with a repeat test within 24 hours. Continue treatment. Test three times weekly until the count is back to 1,500/µL
500 to 999/µL (moderate)	Interrupt treatment and get a hematology consultation. Test daily. Resume once the count is 1,000/µL or higher
Below 500/µL (severe)	Stop treatment and get a hematology consultation. Test daily. Restarting is considered only when the benefits outweigh the risks

Source: Clozaril prescribing information, Table 1, revised June 2025.³ A baseline ANC of at least 1,500/µL is recommended before starting.

Benign ethnic neutropenia has its own thresholds

Some people have a lower baseline neutrophil count that carries no added risk of infection. The label calls this benign ethnic neutropenia, also known as Duffy-null associated neutrophil count, and states that these patients are not at higher risk of clozapine-induced neutropenia. It recommends at least two baseline counts, allows starting at 1,000/µL or higher, and uses a separate table with lower thresholds.³

Fever is a reason to check a count early

The label recommends that the prescriber interrupt clozapine and check an ANC for a temperature of 101.3°F (38.5°C) or higher.³ Fever or a sore throat on clozapine means a call to the prescriber that day.

How large the risk is, and when it happens

The first US surveillance data covered 11,555 patients who received clozapine between February 1990 and April 1991. Agranulocytosis developed in 73 of them, and 2 died of infection. The cumulative incidence was 0.80% at one year, and 61 of the 73 cases occurred within the first three months.⁴

A Finnish national study published in 2024 followed 61,769 people with schizophrenia or schizoaffective disorder for up to 22 years. The cumulative incidence of agranulocytosis was 1.37% with clozapine and 0.13% with other antipsychotics. The excess risk fell steeply over time: the adjusted odds ratio was 36.0 in the first six months of clozapine use and 4.4 after 54 months or more. One of 3,559 people starting clozapine died of clozapine-induced agranulocytosis.⁵

The danger is concentrated early, which is why testing is front-loaded. The label puts the greatest risk in the first 18 weeks.³

What our 2017 study found about the thresholds

In 2015 the FDA lowered the ANC threshold for interrupting clozapine from 1,500/µL to 1,000/µL and removed white blood cell count thresholds from the algorithm. With Mark Olfson, Christoph Correll, and Erica Duncan, I evaluated what that change meant using Veterans Affairs prescribing records from 1999 to 2012.⁶

Of 14,620 patients with schizophrenia, 246 received clozapine, or 1.7%. Among 160 patients starting clozapine, 5 (3.1%) met criteria for treatment interruption in the first year under the former rules, and 1 (0.6%) met them under the 2015 rules. No agranulocytosis was observed during the study period.⁶

We applied the revised rules to historical records, so the study couldn't test safety after the change, and the cohort was small and from one VA network. Within those limits, it suggests that most first-year interruptions under the former algorithm were triggered by counts the current thresholds no longer treat as dangerous.

Where expert consensus is heading

A global Delphi panel published consensus guidelines in Lancet Psychiatry in 2026. The panel recommended a cessation threshold of 1.0 × 10⁹/L, with 0.5 × 10⁹/L for Duffy-null individuals, and recommended discontinuing routine ANC monitoring after two years. It paired that with regular monitoring of other adverse effects, including constipation, metabolic syndrome, and tachycardia.⁷

The US prescribing information has not adopted the two-year stopping point. It still recommends monthly testing from month 13 on.³ Patients should expect their psychiatrist to follow the label and to explain any departure from it.

Whether ending the REMS will increase clozapine use

It may help. It's unlikely to be enough. A 2026 study of 75 countries found that clozapine use from 2014 to 2024 tracked the number of psychiatrists in a country and was unrelated to how strict the blood monitoring rules were.⁸ The remaining barriers likely include prescriber training and comfort, which a regulatory change doesn't address.

Limitations of the evidence

This evidence has limitations. First, the US data were collected under mandatory weekly monitoring, so they describe the risk with testing in place. Second, the consensus recommendations are expert agreement and haven't been tested in a trial. Nevertheless, three decades of data agree: severe neutropenia is uncommon, occurs mostly in the first months, and shows up on a blood test.

Frequently asked questions

Do I still need blood tests on clozapine now that the REMS has ended?

Yes. The FDA removed the REMS program effective June 13, 2025, and the prescribing information still recommends absolute neutrophil count testing weekly for the first 6 months, every 2 weeks through month 12, and monthly after that.^{1, 3}

Does my pharmacy still need my ANC result before filling clozapine?

The federal requirement ended. Since February 24, 2025, the FDA has not expected pharmacies to verify a reported ANC result before dispensing clozapine, and the program was formally removed on June 13, 2025.^{2, 1}

What ANC level stops clozapine?

For patients without benign ethnic neutropenia, the label recommends interrupting treatment when the ANC falls below 1,000/µL and stopping it when the ANC falls below 500/µL. Counts of 1,000 to 1,499/µL call for testing three times weekly while treatment continues.³

How common is agranulocytosis on clozapine?

In US surveillance of 11,555 patients, the cumulative incidence was 0.80% at one year, and most cases occurred in the first three months. A Finnish national study found a cumulative incidence of 1.37% over up to 22 years of follow-up.^{4, 5}

Can someone with benign ethnic neutropenia take clozapine?

Yes. The label states that people with benign ethnic neutropenia are not at increased risk of clozapine-induced neutropenia. It allows starting clozapine with a baseline ANC of 1,000/µL or higher and uses a separate monitoring table.³

In a crisis: call or text 988, or go to the nearest emergency department. A first episode of psychosis belongs in a hospital-based or coordinated specialty care program.

I start and manage clozapine in an outpatient practice in Chelsea, Manhattan. Details are on the schizophrenia care in NYC page. Clozapine should not be stopped, skipped, or restarted without the prescriber. This page is general information and does not replace an evaluation.