REMS for Clozapine: What You Need to Know About ANC Monitoring and Safety Changes in 2026

For years, getting clozapine prescribed for treatment-resistant schizophrenia meant jumping through a maze of paperwork, certifications, and blood test reports. The FDA’s mandatory REMS program made it hard for patients to get this life-changing medication-even when it was the only thing that worked. But on February 24, 2025, everything changed. The FDA removed the mandatory Risk Evaluation and Mitigation Strategy (REMS) for clozapine. That means pharmacies no longer need to verify ANC (Absolute Neutrophil Count) results before filling prescriptions. Patients can now get clozapine faster. Doctors can prescribe it without logging into a federal portal. But here’s the catch: the risk of severe neutropenia hasn’t disappeared. It’s still real. And monitoring hasn’t gone away-it’s just no longer forced by law.

Why Was Clozapine’s REMS Program So Strict?

Clozapine is one of the most effective antipsychotics for people who don’t respond to other medications. Studies show 30-50% of patients with treatment-resistant schizophrenia improve on clozapine, compared to just 10-15% with other second-generation drugs. But it carries a serious risk: agranulocytosis-a dangerous drop in white blood cells that can lead to life-threatening infections. In the 1980s, before clozapine was approved in the U.S., 29 patients died from this side effect in Europe. That’s why the FDA approved it in 1989 with extreme restrictions.

By 2015, those restrictions became a formal REMS program. Every prescriber had to be certified. Every pharmacy had to be certified. Every patient had to be enrolled. And every month, doctors had to submit a Patient Status Form showing the patient’s ANC was above 1,500/μL (or 1,000/μL for those with Benign Ethnic Neutropenia). If the form wasn’t submitted, the pharmacy couldn’t dispense the drug. Even phone calls or faxes weren’t enough after November 2021-you had to use the REMS portal. For many, especially in rural areas or small clinics, the process was a roadblock.

What Changed on February 24, 2025?

The FDA reviewed over 30 years of real-world data. They looked at millions of blood test results from the Department of Veterans Affairs, Brigham and Women’s Hospital, and the FDA’s own Sentinel System. They studied how often patients were monitored, how many cases of severe neutropenia occurred, and whether providers were still following guidelines even without the REMS system.

The answer? Yes, they were.

Healthcare professionals had gotten better at monitoring. ANC checks were still happening at the same rates-weekly for the first 6 months, biweekly from 6 to 12 months, monthly after that. The number of severe neutropenia cases had dropped steadily since 2005, even with REMS in place. The FDA concluded: the program wasn’t adding safety-it was adding burden.

So they removed it. As of February 24, 2025:

• Prescribers no longer need to register with the Clozapine REMS website.
• Pharmacies no longer need certification to dispense clozapine.
• Patient enrollment in the REMS registry is no longer required.
• ANC results no longer need to be reported to a federal database.

But You Still Need to Monitor ANC-Here’s How

Just because the government stopped requiring it doesn’t mean your doctor should stop checking. The FDA still says: “The risk of severe neutropenia is greatest in the first several months of treatment and persists at a lower level thereafter.” The boxed warning on clozapine labels hasn’t changed. Neither has the standard of care.

Here’s what your doctor should still do:

1. Before starting clozapine: Get a baseline ANC test. No exceptions.
2. Weeks 1-18: Weekly ANC tests. This is when the risk is highest.
3. Months 6-12: If ANC stays above 1,500/μL (or 1,000/μL for Benign Ethnic Neutropenia), switch to biweekly checks.
4. After 12 months: Monthly ANC tests, using shared decision-making with the patient.

This schedule isn’t arbitrary. It’s based on decades of data from the VA and other major health systems. A 2023 study in Movement Disorders confirmed this timeline matches when neutropenia risk actually drops. The FDA didn’t change the science-they changed the bureaucracy.

How Has This Affected Access to Clozapine?

Before 2025, only about 12% of Americans with treatment-resistant schizophrenia were on clozapine-even though an estimated 1.1 million people qualify. Why? Because the REMS program created delays. One study found 30% of patients faced weeks-long waits because of paperwork. Pharmacies added 10-15 minutes per prescription just to verify REMS status. Clinics spent an average of 3.2 hours a week just filing forms.

The results? Only 31.7% of eligible patients received clozapine, according to JAMA Psychiatry in 2022. And 42% of doctors said REMS was a reason they didn’t prescribe it.

Now? Things are changing fast. Anthem’s Provider News predicts a 25-30% jump in new clozapine starts over the next two years. Evaluate Pharma upgraded its market forecast from $487 million in 2024 to $612 million by 2026. Independent pharmacies that couldn’t handle the REMS system are now able to fill clozapine prescriptions. Patients in rural areas are getting the drug without driving to a specialty clinic.

What About Safety? Is This Risky?

Some clinicians worry. Without mandatory reporting, could someone slip through the cracks? Could a patient miss a test and not know?

The FDA’s answer: “Healthcare professionals are already doing the right thing.” Their analysis showed that even without REMS, 94% of patients on clozapine had ANC tests within the recommended timeframes. That’s because doctors who prescribe clozapine know the risks. They’ve seen the consequences. They’ve learned from experience.

The American Psychiatric Nurses Association called the REMS removal “a success for both providers and patients.” The Medical Letter noted it would “minimize the burden on the healthcare system.” Even the National Alliance on Mental Illness (NAMI), which once pushed for stricter safeguards, now supports the change.

The bottom line: the risk hasn’t vanished. But the system that tried to control it was broken. The new model trusts professionals to do their jobs-because they already are.

What Should You Do Now?

If you’re a patient on clozapine:

• Don’t stop your ANC tests. Keep them on schedule.
• If your pharmacy asks for REMS paperwork, tell them it’s no longer required as of February 24, 2025.
• Ask your doctor to confirm your ANC schedule. Don’t assume it’s automatic.

If you’re a provider:

• Update your prescribing workflow. Remove REMS verification steps.
• Keep the ANC monitoring schedule. It’s still the standard of care.
• Use the updated FDA-approved prescribing information (Novartis, 2017) as your guide.
• Consider sharing the 2025 Clozapine National Protocol Guidance with your staff.

If you’re a pharmacist:

• You no longer need REMS certification.
• You can dispense clozapine without checking a federal portal.
• Still verify that the patient has had an ANC test within the last 30 days. If not, hold the prescription and contact the prescriber.

What’s Next?

The American Society of Health-System Pharmacists is launching updated clinical guidelines in Q3 2025 to help providers adapt. The FDA will keep watching through the Sentinel System. If neutropenia rates rise, they’ll act. But so far, data shows no increase in cases since the REMS removal.

Clozapine is no longer a drug locked behind red tape. It’s now a tool doctors can use more freely-when the science says it’s needed. The goal was never to stop people from getting clozapine. It was to protect them. And now, protection comes from good medical practice, not government mandates.