FDA Removes REMS Program for Clozapine Despite Neutropenia Risk

The U.S. Food and Drug Administration has removed the Risk Evaluation and Mitigation Strategies (REMS) program for clozapine, effective June 13th, 2025, determining that while neutropenia risk remains, the REMS program may prevent treatment access.

Balancing Safety and Access

The decision marks a significant shift in the FDA's approach to managing the safety profile of this medication. Despite the continued presence of neutropenia risk, the agency concluded that the REMS program is no longer necessary and may actually create barriers to patient treatment.

Risk Evaluation and Mitigation Strategies are FDA-required safety programs designed to manage known or potential serious risks associated with certain medications. These programs can include requirements for prescriber training, patient monitoring, restricted distribution systems, and mandatory enrollment procedures.

Understanding Neutropenia Risk

Neutropenia is a condition characterized by abnormally low levels of neutrophils, a type of white blood cell critical for fighting infections. When neutropenia occurs as a medication side effect, patients face increased vulnerability to serious bacterial and fungal infections that can become life-threatening if not properly managed.

For antipsychotic medications, neutropenia has long been recognized as a serious but relatively rare adverse effect that requires careful monitoring. Healthcare providers typically conduct regular blood tests to detect early signs of neutrophil depletion in patients taking these medications.

Implications for Healthcare Providers

With the removal of the REMS program, prescribers will no longer need to complete mandatory certification requirements or enroll patients in a restricted distribution system. However, the underlying risk of neutropenia has not changed, meaning healthcare professionals must remain vigilant in monitoring patients for signs of this potentially serious side effect.

Pharmacists and prescribers should continue to:

• Educate patients about signs and symptoms of infection
• Conduct baseline and periodic blood count monitoring
• Assess individual patient risk factors
• Maintain awareness of drug interactions that may increase neutropenia risk
• Report adverse events through the FDA's MedWatch program

Impact on Patient Access

The FDA's decision reflects growing recognition that overly restrictive safety programs can create unintended barriers to necessary treatment. REMS programs, while designed to protect patients, can complicate prescribing and dispensing processes, potentially delaying or preventing access to needed medications.

The FDA's Center for Drug Evaluation and Research provides information about drug risks and benefits to health care professionals and patients, especially when that information has generated a specific concern. This communication represents the agency's ongoing effort to balance safety monitoring with treatment accessibility.

Broader Context

The FDA has increased communication about the safety of certain drugs in recent years as part of enhanced post-marketing surveillance efforts. The agency has begun making information on potential drug risks available to the public earlier — often while evaluating safety data and determining whether any regulatory action is warranted.

This decision reflects the FDA's evolving approach to drug safety management, recognizing that risk mitigation must be balanced against practical considerations of treatment access and healthcare system burden.

What's Next

Healthcare providers should review their current protocols for prescribing and monitoring this antipsychotic medication. While formal REMS requirements have been eliminated, best practices for neutropenia monitoring should continue.

The FDA will continue post-market surveillance of this medication through its standard safety monitoring systems, including the Adverse Event Reporting System (FAERS) and the Sentinel Initiative.

Pharmacists and other healthcare professionals seeking additional information should consult the medication's current prescribing information and monitor FDA communications for any further updates regarding this drug's safety profile.