REMS for Clozapine: What Changed in 2025 and How ANC Monitoring Works Now

Before February 24, 2025, getting clozapine wasn’t just about a prescription. If you or someone you know was taking this powerful medication for treatment-resistant schizophrenia, you were stuck in a complex, mandatory system called the REMS - Risk Evaluation and Mitigation Strategy. It wasn’t just paperwork. It was weekly blood tests, monthly forms, certified pharmacies, and delays that could keep someone from getting the one drug that might actually work for them. Now? That system is gone. The FDA officially removed the mandatory REMS program for clozapine, and here’s what that really means for patients, doctors, and pharmacies.

Why Clozapine Was Different

Clozapine isn’t like other antipsychotics. It’s the last resort - the drug doctors turn to when everything else has failed. For people with schizophrenia who haven’t responded to at least two other medications, clozapine can cut hospitalizations, reduce hallucinations, and even lower suicide risk. Studies show it works for 30% to 50% of those who’ve tried everything else. But it comes with a serious risk: severe neutropenia, a drop in white blood cells that can lead to life-threatening infections. That’s why, back in 1989, the FDA put strict controls on it. By 2015, those controls became the REMS program - a mandatory, government-run system that required every step of clozapine use to be tracked.

Under REMS, prescribers had to be certified. Pharmacies had to be certified. Patients had to be enrolled. And every time a patient needed a refill, their latest Absolute Neutrophil Count (ANC) had to be reported to a central registry. No report? No pill. It was designed to prevent deaths. But it also created barriers.

How ANC Monitoring Worked Under REMS

The ANC test measured the number of neutrophils - a type of white blood cell - in the blood. The lower the count, the higher the infection risk. The REMS program had very specific rules:

• Before starting clozapine: One baseline ANC test.
• Weeks 1-18: Weekly ANC tests. This was the highest-risk period.
• Months 6-12: Every two weeks (if ANC stayed above 1,500/μL).
• After 12 months: Monthly checks.

Patients with Benign Ethnic Neutropenia - often people of African, Middle Eastern, or Mediterranean descent - had a lower threshold: ANC above 1,000/μL was considered safe. But even then, every result had to be submitted to the REMS system. Prescribers filled out a monthly Patient Status Form. Pharmacies couldn’t just call in a verification - they had to log into the REMS portal or call a dedicated center. The whole process added 10 to 15 minutes per prescription. Clinics spent an average of 3.2 hours per week just on REMS paperwork.

The Big Change: REMS Was Removed

On February 24, 2025, the FDA made a landmark decision: clozapine REMS is no longer mandatory. This wasn’t a mistake. It wasn’t rushed. The FDA spent over a year reviewing real-world data from the Sentinel System, the Department of Veterans Affairs, and Brigham and Women’s Hospital. They looked at tens of thousands of patient records. They checked whether doctors were still monitoring ANC - even without being forced to.

The answer? Yes.

Doctors were already doing it. Pharmacies were still checking results. The risk of neutropenia hadn’t gone up. The FDA concluded that the medical community had learned how to manage this risk on its own. The mandatory system wasn’t improving safety - it was just making access harder.

Now, prescribers don’t need certification. Pharmacies don’t need to report ANC results. Patients don’t need to be enrolled. No forms. No portals. No delays.

What’s Still Required

Let’s be clear: the risk of severe neutropenia hasn’t disappeared. It’s still real. That’s why the FDA didn’t remove the warning - it strengthened it. All clozapine labels still carry a Boxed Warning - the strongest kind - about this risk. The prescribing information from Novartis hasn’t changed on the monitoring schedule. The same weekly, biweekly, monthly guidelines still apply. The only difference? You’re not being watched by the government anymore. You’re being watched by your doctor.

Doctors are still expected to:

• Check ANC before starting clozapine.
• Test weekly for the first 6 months.
• Test every two weeks from 6 to 12 months.
• Test monthly after 12 months.

And if ANC drops below 1,500/μL (or 1,000/μL for those with Benign Ethnic Neutropenia), clozapine should be paused or stopped - just like before. The rules didn’t change. The enforcement did.

Why This Matters

Before the REMS removal, only about 12% of Americans with treatment-resistant schizophrenia were getting clozapine - even though studies show it works for nearly half of them. Why? Because the system was broken. A 2023 study in Schizophrenia Bulletin found clinics without a dedicated REMS coordinator were almost four times less likely to start patients on clozapine. Rural pharmacies couldn’t handle the paperwork. Patients in low-income areas waited weeks for a blood test to be submitted. NAMI reported that 30% of patients faced delays in getting their medication.

Now, those barriers are gone. A psychiatrist in rural Montana can prescribe clozapine without waiting for a certification number. A pharmacy in Atlanta can fill the prescription without logging into a federal portal. A patient doesn’t have to miss work to submit a form. This isn’t just convenience - it’s access. And access saves lives.

What’s Next?

The American Society of Health-System Pharmacists is rolling out updated guidelines in Q3 2025 to help clinicians stay on track. The FDA will keep watching through the Sentinel System, tracking neutropenia cases in real time. Industry analysts predict clozapine use will jump 25% to 30% over the next two years. Market forecasts now put clozapine sales at $612 million by 2026 - up from $487 million in 2024.

Some worry this change could lead to lapses. But the data says otherwise. The VA, which has been monitoring ANC without federal mandates for years, saw no increase in severe neutropenia cases. The same was true in large health systems that stopped REMS reporting early. The medical community didn’t need a government system to do the right thing. They just needed the freedom to do it.

What Patients Should Do Now

If you’re taking clozapine:

• Keep getting your ANC tests on schedule - don’t skip them.
• Make sure your doctor knows your ANC results every time.
• If your ANC drops below 1,500/μL (or 1,000/μL if you have Benign Ethnic Neutropenia), don’t panic - but do contact your prescriber immediately.
• Don’t assume the drug is safer now. It’s just easier to get.

If you’re considering clozapine:

• Ask your psychiatrist: ‘What’s my ANC history?’
• Ask: ‘How often will you check my blood?’
• Ask: ‘Will you stop the medication if my count drops too low?’

The decision to remove REMS wasn’t about lowering standards. It was about trusting the people who treat patients every day. And for the first time in decades, the system is finally working for the patient - not against them.