REMS for Clozapine: ANC Monitoring and Safety Enrollment After FDA Changes in 2025

Before February 24, 2025, getting clozapine wasn’t just about writing a prescription. It meant jumping through a maze of paperwork, certifications, and mandatory blood test reporting. For patients with treatment-resistant schizophrenia - the people who needed clozapine the most - this system often meant delays, frustration, and sometimes, no medication at all. Now, that’s all changed. The FDA has officially removed the mandatory Risk Evaluation and Mitigation Strategy (REMS) for clozapine. But here’s what you need to know: clozapine is still dangerous if not monitored. The rules just got simpler.

What Was the Clozapine REMS Program?

The Clozapine REMS program started in 2015 as a way to prevent a rare but deadly side effect: severe neutropenia, which can turn into agranulocytosis. This condition wipes out white blood cells, leaving the body defenseless against infection. The risk is highest in the first 6 months of treatment, but it never fully disappears. So, the FDA required every prescriber, pharmacy, and patient to enroll in a national system. Prescribers had to get certified. Pharmacies had to be certified. Patients had to submit monthly blood test results - specifically, their Absolute Neutrophil Count (ANC) - before they could get their next refill.

That meant if your ANC dropped below 1,500/μL (or 1,000/μL if you had benign ethnic neutropenia), the pharmacy couldn’t fill your prescription. No exceptions. No exceptions meant delays. And delays meant people went without one of the most effective antipsychotics on the market.

Why Did the FDA Remove the REMS?

The FDA didn’t remove the REMS because the risk went away. It didn’t. The risk of severe neutropenia is still real - about 0.8% of patients develop it, mostly in the first few months. But after years of data collection, the agency found something surprising: doctors and pharmacists were already doing the right thing.

Studies from the Department of Veterans Affairs, Brigham and Women’s Hospital, and the FDA’s own Sentinel System showed that even without the mandatory reporting system, healthcare providers were still checking ANC levels weekly for the first 6 months, biweekly until 12 months, and monthly after that. They were following the same guidelines that had been in place since 2005. There was no evidence of widespread lapses in monitoring.

Meanwhile, the administrative burden was crushing. Clinics spent an average of 3.2 hours per week just filling out forms. Pharmacies added 10-15 minutes per clozapine prescription just to verify compliance. Prescribers had to re-certify every two years. Patients had to log in to a portal, mail forms, or call a call center just to get their medicine. The American Psychiatric Association reported that 42% of clinicians said the REMS was a reason they didn’t prescribe clozapine - even when it was clearly needed.

What Changed on February 24, 2025?

As of that date:

• Prescribers no longer need to register with the Clozapine REMS website.
• Pharmacies no longer need to be certified to dispense clozapine.
• Patients no longer have to submit ANC results to any central registry.
• Telecom verification and online portals are no longer required.

That’s it. The system is gone. But here’s the critical part: ANC monitoring is still recommended. The FDA didn’t say, “Stop checking blood counts.” They said, “Use your clinical judgment.”

The prescribing information for clozapine (CLOZARIL) still says:

• Baseline ANC before starting
• Weekly ANC for the first 6 months
• Biweekly ANC from 6 to 12 months
• Monthly ANC after 12 months

And the Boxed Warning - the strongest warning the FDA can put on a drug - is still there. It still says: “Clozapine can cause severe neutropenia. Monitor ANC regularly.”

What Does This Mean for Patients?

For patients, this is a win. No more delays. No more paperwork. No more being denied a refill because a form got lost in the mail. A patient in rural Montana or a small town in Texas can now get clozapine without having to track down a clinic with a REMS coordinator. A 2023 study found clinics without dedicated REMS staff were 3.7 times less likely to start patients on clozapine. That barrier is gone.

But patients still need to get their blood drawn. If you’re on clozapine, your doctor should still be ordering ANC tests on the same schedule. If you miss a test, your pharmacist might still ask why - not because the law requires it, but because it’s the standard of care. Your doctor still has to decide: is this patient safe to keep on the drug?

What Does This Mean for Doctors and Pharmacists?

For prescribers, the administrative load has dropped dramatically. No more logging into a portal. No more re-certification. No more monthly Patient Status Forms. That’s time you can spend talking to your patient instead of filling out paperwork.

But you still need to monitor. The FDA’s decision didn’t change clinical guidelines - it just removed the enforcement. You’re still expected to follow the same ANC schedule. If you stop monitoring, and something goes wrong, you’re still liable. The legal standard didn’t change. The burden did.

Pharmacists are in a gray zone. They can now dispense clozapine without checking the REMS portal. But they’re still expected to verify that ANC monitoring is happening. Many will still ask, “Has the patient had their last ANC?” That’s not because the FDA requires it - it’s because they’re still practicing safe medicine. Some pharmacies may stop asking. Others will keep checking. It’s now up to each provider.

What About the Risk? Is It Still Real?

Yes. The risk hasn’t disappeared. The FDA’s own data shows:

• Most cases of severe neutropenia happen in the first 18 weeks.
• After 12 months, the risk drops, but it’s still present.
• Patients with a history of neutropenia, older adults, and those on other bone marrow-suppressing drugs are at higher risk.

That’s why the Boxed Warning stays. That’s why guidelines haven’t changed. The FDA didn’t say, “Stop monitoring.” They said, “You’ve been doing it right. We trust you.”

What’s Next?

The American Society of Health-System Pharmacists is rolling out updated clinical guidelines in Q3 2025 to reinforce that ANC monitoring remains essential. The FDA will keep watching through the Sentinel System - a national database that tracks real-world drug safety. So far, early data shows no spike in neutropenia cases since the REMS removal.

Market analysts expect clozapine use to rise by 25-30% over the next two years. In 2024, only about 12% of eligible patients in the U.S. were on clozapine. That’s not because it doesn’t work - it’s because the system made it too hard. Now, that’s changing.

For patients with treatment-resistant schizophrenia, this is more than a policy shift. It’s a chance to get the medicine that might save their life - without the red tape that stood in the way.

What Should You Do Now?

If you’re a patient:

• Keep getting your ANC tested on schedule - weekly, then biweekly, then monthly.
• Don’t skip tests just because the REMS is gone.
• Ask your doctor: “When is my next blood test due?”

If you’re a prescriber:

• Stop using the Clozapine REMS portal. It’s no longer active.
• Continue following the ANC monitoring schedule in the prescribing information.
• Document your monitoring plan in the chart - it’s still your responsibility.

If you’re a pharmacist:

• You no longer need to verify REMS enrollment.
• But you should still confirm that ANC monitoring is current - it’s still standard care.
• Update your pharmacy systems to remove REMS checks.