The U.S. Food and Drug Administration (FDA) has announced a significant policy shift regarding the antipsychotic medication clozapine. On February 24, the agency declared the cessation of the Risk Evaluation and Mitigation Strategy (REMS) program, initially established in 2015. This decision signals a potential change in how clozapine is prescribed and dispensed, though the impact remains uncertain. The REMS program required physicians and pharmacists to obtain certification to prescribe and dispense clozapine, and mandated monthly submission of patient status forms detailing Absolute Neutrophil Count (ANC) levels to determine the appropriateness of continued treatment.
The FDA's decision follows a panel meeting held in November 2024, where concerns about the REMS program's restrictive nature were discussed. Despite ending the program, the FDA continues to recommend monitoring ANC levels according to the drug's labeling due to the risk of severe neutropenia, a condition characterized by dangerously low levels of neutrophils, a type of white blood cell.
The REMS program had undergone several updates since its inception, reflecting ongoing evaluation and modifications to address emerging challenges in the clinical use of clozapine. Nonetheless, the program faced criticism for hindering clinicians' ability to prescribe the medication. Some members of the FDA advisory committee noted that the REMS requirements discouraged prescribing, thereby limiting access for patients who could benefit from clozapine.
“Some larger chain pharmacies have implemented requirements beyond the FDA’s REMS program requiring their staff to enter patients’ recent ANC values in their own internal system prior to dispensing clozapine,” – The Angry Moms group
Additionally, insurance plans often still require a REMS Dispense Authorization (RDA) code to approve pharmacy claims for clozapine, further complicating access.
“Some insurance plans which pay for prescription medications still require a REMS Dispense Authorization (RDA) code to pay for a clozapine pharmacy claim.” – The Angry Moms group
Dr. Robert Cotes, a prominent figure in psychiatric medicine, highlighted that while the risk of neutropenia significantly decreases after a year of treatment, the necessity for weekly blood testing during the initial six months poses substantial challenges for patients lacking adequate resources and support.
“It’s not clear whether ending the REMS will reassure providers," said Cotes. But he added that he is “optimistic that it will ultimately ease the burden on patients to make sure their clozapine is continued without interruption.”
“is just one of many barriers to clozapine’s wider use.” – Cotes
Dr. Walter Dunn echoed concerns about clozapine's broader issues beyond the REMS program, emphasizing that these challenges could still deter clinicians from prescribing the drug.
“There are a whole host of other issues associated with clozapine," that are “more concerning," – Walter Dunn, MD, PhD
While some experts express optimism that removing REMS could facilitate easier access to clozapine, others remain skeptical. Dr. Dunn emphasized that multiple barriers persist, potentially affecting prescribers' willingness to adopt clozapine more widely.
“Ending the REMS might not increase the number of clinicians willing to prescribe clozapine,” – Walter Dunn, MD, PhD
Nevertheless, investigators have emphasized that despite its complexities, clozapine is an essential treatment option.
“warrants prudent use,” – investigators (authors of a meta-analysis in The Lancet Psychiatry)
Dan Siskind and colleagues reinforced this sentiment in an editorial, asserting clozapine's efficacy.
“We believe clozapine remains the most effective medication for treatment-resistant schizophrenia,” – Dan Siskind and colleagues (authors of an accompanying editorial)
Leave a Reply